Livestock abundance predicts vampire bat demography, immune profiles and bacterial infection risk

PubMed Central

Czirják, Gábor Á.; Volokhov, Dmitriy V.; Carrera, Jorge E.; Camus, Melinda S.; Navara, Kristen J.; Chizhikov, Vladimir E.; Fenton, M. Brock; Simmons, Nancy B.; Recuenco, Sergio E.; Gilbert, Amy T.

2018-01-01

Human activities create novel food resources that can alter wildlife–pathogen interactions. If resources amplify or dampen, pathogen transmission probably depends on both host ecology and pathogen biology, but studies that measure responses to provisioning across both scales are rare. We tested these relationships with a 4-year study of 369 common vampire bats across 10 sites in Peru and Belize that differ in the abundance of livestock, an important anthropogenic food source. We quantified innate and adaptive immunity from bats and assessed infection with two common bacteria. We predicted that abundant livestock could reduce starvation and foraging effort, allowing for greater investments in immunity. Bats from high-livestock sites had higher microbicidal activity and proportions of neutrophils but lower immunoglobulin G and proportions of lymphocytes, suggesting more investment in innate relative to adaptive immunity and either greater chronic stress or pathogen exposure. This relationship was most pronounced in reproductive bats, which were also more common in high-livestock sites, suggesting feedbacks between demographic correlates of provisioning and immunity. Infection with both Bartonella and haemoplasmas were correlated with similar immune profiles, and both pathogens tended to be less prevalent in high-livestock sites, although effects were weaker for haemoplasmas. These differing responses to provisioning might therefore reflect distinct transmission processes. Predicting how provisioning alters host–pathogen interactions requires considering how both within-host processes and transmission modes respond to resource shifts. This article is part of the theme issue ‘Anthropogenic resource subsidies and host–parasite dynamics in wildlife’. PMID:29531144

A minimal model for multiple epidemics and immunity spreading.

PubMed

Sneppen, Kim; Trusina, Ala; Jensen, Mogens H; Bornholdt, Stefan

2010-10-18

Pathogens and parasites are ubiquitous in the living world, being limited only by availability of suitable hosts. The ability to transmit a particular disease depends on competing infections as well as on the status of host immunity. Multiple diseases compete for the same resource and their fate is coupled to each other. Such couplings have many facets, for example cross-immunization between related influenza strains, mutual inhibition by killing the host, or possible even a mutual catalytic effect if host immunity is impaired. We here introduce a minimal model for an unlimited number of unrelated pathogens whose interaction is simplified to simple mutual exclusion. The model incorporates an ongoing development of host immunity to past diseases, while leaving the system open for emergence of new diseases. The model exhibits a rich dynamical behavior with interacting infection waves, leaving broad trails of immunization in the host population. This obtained immunization pattern depends only on the system size and on the mutation rate that initiates new diseases.

Granuloma Transplantation: An Approach to Study Mycobacterium–Host Interactions

PubMed Central

Harding, Jeffrey S.; Schreiber, Heidi A.; Sandor, Matyas

2011-01-01

The host–pathogen biology during infection with Mycobacterium tuberculosis is incredibly complex and despite accelerating progress in research, remains poorly understood. Our limited understanding hinders the development of new drugs, next generation vaccines, and novel therapies. The granuloma is the site where mycobacteria are both controlled and allowed to persist, but it remains one of the least studied aspects of the host–pathogen relationship. Here, we review the development, application, potential uses, and limitations of a novel model of granuloma transplantation as a tool to study specific host–pathogen interactions that have been difficult to probe. Application of this new model has already contributed to our understanding of granuloma cell traffic, repopulation, and the relationship between systemic immunity and mycobacteria-containing granulomas. The data collected highlight the dynamic interaction between systemic and local immune processes and support a paradigm that defines the granuloma as a highly dynamic structure. Granuloma transplantation also has special potential as a novel latency model that can contribute to our understanding of host protection factors and bacterial mutants, and serve as a platform for drug testing. PMID:22180751

Phytophthora capsici-tomato interaction features dramatic shifts in gene expression associated with a hemi-biotrophic lifestyle.

PubMed

Jupe, Julietta; Stam, Remco; Howden, Andrew J M; Morris, Jenny A; Zhang, Runxuan; Hedley, Pete E; Huitema, Edgar

2013-06-25

Plant-microbe interactions feature complex signal interplay between pathogens and their hosts. Phytophthora species comprise a destructive group of fungus-like plant pathogens, collectively affecting a wide range of plants important to agriculture and natural ecosystems. Despite the availability of genome sequences of both hosts and microbes, little is known about the signal interplay between them during infection. In particular, accurate descriptions of coordinate relationships between host and microbe transcriptional programs are lacking. Here, we explore the molecular interaction between the hemi-biotrophic broad host range pathogen Phytophthora capsici and tomato. Infection assays and use of a composite microarray allowed us to unveil distinct changes in both P. capsici and tomato transcriptomes, associated with biotrophy and the subsequent switch to necrotrophy. These included two distinct transcriptional changes associated with early infection and the biotrophy to necrotrophy transition that may contribute to infection and completion of the P. capsici lifecycle Our results suggest dynamic but highly regulated transcriptional programming in both host and pathogen that underpin P. capsici disease and hemi-biotrophy. Dynamic expression changes of both effector-coding genes and host factors involved in immunity, suggests modulation of host immune signaling by both host and pathogen. With new unprecedented detail on transcriptional reprogramming, we can now explore the coordinate relationships that drive host-microbe interactions and the basic processes that underpin pathogen lifestyles. Deliberate alteration of lifestyle-associated transcriptional changes may allow prevention or perhaps disruption of hemi-biotrophic disease cycles and limit damage caused by epidemics.

A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus aureus: Comparing Behavior of Pathogen Perturbed and Unperturbed Pathway

PubMed Central

Tomar, Namrata; De, Rajat K.

2013-01-01

Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the Staphylococcal Enterotoxin (SE)-challenged system within the range of normal behavior. PMID:24324645

Immunity to intestinal pathogens: lessons learned from Salmonella

PubMed Central

McSorley, Stephen J.

2014-01-01

Summary Salmonella are a common source of food or water-borne infection and cause a wide range of clinical disease in human and animal hosts. Salmonella are relatively easy to culture and manipulate in a laboratory setting, and the infection of laboratory animals induces robust innate and adaptive immune responses. Thus, immunologists have frequently turned to Salmonella infection models to expand understanding of immunity to intestinal pathogens. In this review, I summarize current knowledge of innate and adaptive immunity to Salmonella and highlight features of this response that have emerged from recent studies. These include the heterogeneity of the antigen-specific T-cell response to intestinal infection, the prominence of microbial mechanisms to impede T and B-cell responses, and the contribution of non-cognate pathways for elicitation of T-cell effector functions. Together, these different issues challenge an overly simplistic view of host-pathogen interaction during mucosal infection but also allow deeper insight into the real-world dynamic of protective immunity to intestinal pathogens. PMID:24942689

Species interactions may help explain the erratic periodicity of whooping cough dynamics.

PubMed

Bhattacharyya, Samit; Ferrari, Matthew J; Bjørnstad, Ottar N

2017-12-14

Incidence of whooping cough exhibits variable dynamics across time and space. The periodicity of this disease varies from annual to five years in different geographic regions in both developing and developed countries. Many hypotheses have been put forward to explain this variability such as nonlinearity and seasonality, stochasticity, variable recruitment of susceptible individuals via birth, immunization, and immune boosting. We propose an alternative hypothesis to describe the variability in periodicity - the intricate dynamical variability of whooping cough may arise from interactions between its dominant etiological agents of Bordetella pertussis and Bordetella parapertussis. We develop a two-species age-structured model, where two pathogens are allowed to interact by age-dependent convalescence of individuals with severe illness from infections. With moderate strength of interactions, the model exhibits multi-annual coexisting attractors that depend on the R 0 of the two pathogens. We also examine how perturbation from case importation and noise in transmission may push the system from one dynamical regime to another. The coexistence of multi-annual cycles and the behavior of switching between attractors suggest that variable dynamics of whopping cough could be an emergent property of its multi-agent etiology. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Plant-Pathogen Warfare under Changing Climate Conditions.

PubMed

Velásquez, André C; Castroverde, Christian Danve M; He, Sheng Yang

2018-05-21

Global environmental changes caused by natural and human activities have accelerated in the past 200 years. The increase in greenhouse gases is predicted to continue to raise global temperature and change water availability in the 21 st century. In this Review, we explore the profound effect the environment has on plant diseases - a susceptible host will not be infected by a virulent pathogen if the environmental conditions are not conducive for disease. The change in CO 2 concentrations, temperature, and water availability can have positive, neutral, or negative effects on disease development, as each disease may respond differently to these variations. However, the concept of disease optima could potentially apply to all pathosystems. Plant resistance pathways, including pattern-triggered immunity to effector-triggered immunity, RNA interference, and defense hormone networks, are all affected by environmental factors. On the pathogen side, virulence mechanisms, such as the production of toxins and virulence proteins, as well as pathogen reproduction and survival are influenced by temperature and humidity. For practical reasons, most laboratory investigations into plant-pathogen interactions at the molecular level focus on well-established pathosystems and use a few static environmental conditions that capture only a fraction of the dynamic plant-pathogen-environment interactions that occur in nature. There is great need for future research to increasingly use dynamic environmental conditions in order to fully understand the multidimensional nature of plant-pathogen interactions and produce disease-resistant crop plants that are resilient to climate change. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using an agent-based model to analyze the dynamic communication network of the immune response

PubMed Central

2011-01-01

Background The immune system behaves like a complex, dynamic network with interacting elements including leukocytes, cytokines, and chemokines. While the immune system is broadly distributed, leukocytes must communicate effectively to respond to a pathological challenge. The Basic Immune Simulator 2010 contains agents representing leukocytes and tissue cells, signals representing cytokines, chemokines, and pathogens, and virtual spaces representing organ tissue, lymphoid tissue, and blood. Agents interact dynamically in the compartments in response to infection of the virtual tissue. Agent behavior is imposed by logical rules derived from the scientific literature. The model captured the agent-to-agent contact history, and from this the network topology and the interactions resulting in successful versus failed viral clearance were identified. This model served to integrate existing knowledge and allowed us to examine the immune response from a novel perspective directed at exploiting complex dynamics, ultimately for the design of therapeutic interventions. Results Analyzing the evolution of agent-agent interactions at incremental time points from identical initial conditions revealed novel features of immune communication associated with successful and failed outcomes. There were fewer contacts between agents for simulations ending in viral elimination (win) versus persistent infection (loss), due to the removal of infected agents. However, early cellular interactions preceded successful clearance of infection. Specifically, more Dendritic Agent interactions with TCell and BCell Agents, and more BCell Agent interactions with TCell Agents early in the simulation were associated with the immune win outcome. The Dendritic Agents greatly influenced the outcome, confirming them as hub agents of the immune network. In addition, unexpectedly high frequencies of Dendritic Agent-self interactions occurred in the lymphoid compartment late in the loss outcomes. Conclusions An agent-based model capturing several key aspects of complex system dynamics was used to study the emergent properties of the immune response to viral infection. Specific patterns of interactions between leukocyte agents occurring early in the response significantly improved outcome. More interactions at later stages correlated with persistent inflammation and infection. These simulation experiments highlight the importance of commonly overlooked aspects of the immune response and provide insight into these processes at a resolution level exceeding the capabilities of current laboratory technologies. PMID:21247471

Network Analysis Reveals a Common Host-Pathogen Interaction Pattern in Arabidopsis Immune Responses.

PubMed

Li, Hong; Zhou, Yuan; Zhang, Ziding

2017-01-01

Many plant pathogens secrete virulence effectors into host cells to target important proteins in host cellular network. However, the dynamic interactions between effectors and host cellular network have not been fully understood. Here, an integrative network analysis was conducted by combining Arabidopsis thaliana protein-protein interaction network, known targets of Pseudomonas syringae and Hyaloperonospora arabidopsidis effectors, and gene expression profiles in the immune response. In particular, we focused on the characteristic network topology of the effector targets and differentially expressed genes (DEGs). We found that effectors tended to manipulate key network positions with higher betweenness centrality. The effector targets, especially those that are common targets of an individual effector, tended to be clustered together in the network. Moreover, the distances between the effector targets and DEGs increased over time during infection. In line with this observation, pathogen-susceptible mutants tended to have more DEGs surrounding the effector targets compared with resistant mutants. Our results suggest a common plant-pathogen interaction pattern at the cellular network level, where pathogens employ potent local impact mode to interfere with key positions in the host network, and plant organizes an in-depth defense by sequentially activating genes distal to the effector targets.

Immune subversion by chromatin manipulation: a 'new face' of host-bacterial pathogen interaction.

PubMed

Arbibe, Laurence

2008-08-01

Bacterial pathogens have evolved various strategies to avoid immune surveillance, depending of their in vivo'lifestyle'. The identification of few bacterial effectors capable to enter the nucleus and modifying chromatin structure in host raises the fascinating questions of how pathogens modulate chromatin structure and why. Chromatin is a dynamic structure that maintains the stability and accessibility of the host DNA genome to the transcription machinery. This review describes the various strategies used by pathogens to interface with host chromatin. In some cases, chromatin injury can be a strategy to take control of major cellular functions, such as the cell cycle. In other cases, manipulation of chromatin structure at specific genomic locations by modulating epigenetic information provides a way for the pathogen to impose its own transcriptional signature onto host cells. This emerging field should strongly influence our understanding of chromatin regulation at interphase nucleus and may provide invaluable openings to the control of immune gene expression in inflammatory and infectious diseases.

Vector-Borne Pathogen and Host Evolution in a Structured Immuno-Epidemiological System.

PubMed

Gulbudak, Hayriye; Cannataro, Vincent L; Tuncer, Necibe; Martcheva, Maia

2017-02-01

Vector-borne disease transmission is a common dissemination mode used by many pathogens to spread in a host population. Similar to directly transmitted diseases, the within-host interaction of a vector-borne pathogen and a host's immune system influences the pathogen's transmission potential between hosts via vectors. Yet there are few theoretical studies on virulence-transmission trade-offs and evolution in vector-borne pathogen-host systems. Here, we consider an immuno-epidemiological model that links the within-host dynamics to between-host circulation of a vector-borne disease. On the immunological scale, the model mimics antibody-pathogen dynamics for arbovirus diseases, such as Rift Valley fever and West Nile virus. The within-host dynamics govern transmission and host mortality and recovery in an age-since-infection structured host-vector-borne pathogen epidemic model. By considering multiple pathogen strains and multiple competing host populations differing in their within-host replication rate and immune response parameters, respectively, we derive evolutionary optimization principles for both pathogen and host. Invasion analysis shows that the [Formula: see text] maximization principle holds for the vector-borne pathogen. For the host, we prove that evolution favors minimizing case fatality ratio (CFR). These results are utilized to compute host and pathogen evolutionary trajectories and to determine how model parameters affect evolution outcomes. We find that increasing the vector inoculum size increases the pathogen [Formula: see text], but can either increase or decrease the pathogen virulence (the host CFR), suggesting that vector inoculum size can contribute to virulence of vector-borne diseases in distinct ways.

Integrated Immune and Cardiovascular Function in Pancrustacea: Lessons from the Insects.

PubMed

Hillyer, Julián F

2015-11-01

When pathogens invade the insect hemocoel (body cavity) they immediately confront two major forces: immune-responses and circulatory currents. The immune response is mediated by circulating and sessile hemocytes, the fat body, the midgut, and the salivary glands. These tissues drive cellular and humoral immune processes that kill pathogens via phagocytosis, melanization, lysis, encapsulation, and nodulation. Moreover, immune-responses take place within a three-dimensional and dynamic space that is governed by the forces of the circulatory system. The circulation of hemolymph (insect blood) is primarily controlled by the wave-like contraction of a dorsal vessel, which is a muscular tube that extends the length of the insect and is divided into a thoracic aorta and an abdominal heart. Distributed along the heart are valves, called ostia, that allow hemolymph to enter the vessel. Once inside the heart, hemolymph is sequentially propelled to the anterior and to the posterior of the body. During an infection, circulatory currents sweep small pathogens to all regions of the body. As they circulate, pathogens encounter immune factors of the insect that range from soluble cytotoxic peptides to phagocytic hemocytes. A prominent location for these encounters is the surface of the heart. Specifically, periostial hemocytes aggregate in the extracardiac regions that flank the heart's ostia (the periostial regions) and phagocytoze pathogens in areas of high flow of hemolymph. This review summarizes the biology of the immune and circulatory systems of insects, including how these two systems have co-adapted to fight infection. This review also compares the immune and circulatory systems of insects to that of crustaceans, and details how attachment of hemocytes to cardiac tissues and the biology of the lymphoid organ demonstrate that dynamic interactions between the immune and circulatory systems also occur in lineages of crustaceans. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Independently evolved virulence effectors converge onto hubs in a plant immune system network.

PubMed

Mukhtar, M Shahid; Carvunis, Anne-Ruxandra; Dreze, Matija; Epple, Petra; Steinbrenner, Jens; Moore, Jonathan; Tasan, Murat; Galli, Mary; Hao, Tong; Nishimura, Marc T; Pevzner, Samuel J; Donovan, Susan E; Ghamsari, Lila; Santhanam, Balaji; Romero, Viviana; Poulin, Matthew M; Gebreab, Fana; Gutierrez, Bryan J; Tam, Stanley; Monachello, Dario; Boxem, Mike; Harbort, Christopher J; McDonald, Nathan; Gai, Lantian; Chen, Huaming; He, Yijian; Vandenhaute, Jean; Roth, Frederick P; Hill, David E; Ecker, Joseph R; Vidal, Marc; Beynon, Jim; Braun, Pascal; Dangl, Jeffery L

2011-07-29

Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins, and ~8000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies.

Epidemics with pathogen mutation on small-world networks

NASA Astrophysics Data System (ADS)

Shao, Zhi-Gang; Tan, Zhi-Jie; Zou, Xian-Wu; Jin, Zhun-Zhi

2006-05-01

We study the dynamical behavior of the epidemiological model with pathogen mutation on small-world networks, and discuss the influence of the immunity duration τR, the cross-immunity threshold hthr, and system size N on epidemic dynamics. A decaying oscillation occurs because of the interplay between the immune response and the pathogen mutation. These results have implications for the interpretation of longitudinal epidemiological data on strain abundance, and they will be helpful to assess the threat of highly pathogenic and mutative viruses, such as avian influenza.

The metabolic pace-of-life model: incorporating ectothermic organisms into the theory of vertebrate ecoimmunology.

PubMed

Sandmeier, Franziska C; Tracy, Richard C

2014-09-01

We propose a new heuristic model that incorporates metabolic rate and pace of life to predict a vertebrate species' investment in adaptive immune function. Using reptiles as an example, we hypothesize that animals with low metabolic rates will invest more in innate immunity compared with adaptive immunity. High metabolic rates and body temperatures should logically optimize the efficacy of the adaptive immune system--through rapid replication of T and B cells, prolific production of induced antibodies, and kinetics of antibody--antigen interactions. In current theory, the precise mechanisms of vertebrate immune function oft are inadequately considered as diverse selective pressures on the evolution of pathogens. We propose that the strength of adaptive immune function and pace of life together determine many of the important dynamics of host-pathogen evolution, namely, that hosts with a short lifespan and innate immunity or with a long lifespan and strong adaptive immunity are expected to drive the rapid evolution of their populations of pathogens. Long-lived hosts that rely primarily on innate immune functions are more likely to use defense mechanisms of tolerance (instead of resistance), which are not expected to act as a selection pressure for the rapid evolution of pathogens' virulence. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Plasmodesmal regulation during plant-pathogen interactions.

PubMed

Cheval, Cecilia; Faulkner, Christine

2018-01-01

Contents Summary 62 I. Introduction 62 II. Plasmodesmal regulation is an innate defence response 63 III. Reactive oxygen species regulate plasmodesmal function 63 IV. Plasmodesmal regulation by and of defence-associated small molecules 64 V. Plasmodesmata facilitate systemic defence signalling 64 VI. Virulent pathogens exploit plasmodesmata 66 VII. Outlook 66 Acknowledgements 66 References 66 SUMMARY: Plasmodesmata (PD) are plasma membrane-lined pores that connect neighbouring plant cells, bridging the cell wall and establishing cytoplasmic and membrane continuity between cells. PD are dynamic structures regulated by callose deposition in a variety of stress and developmental contexts. This process crudely controls the aperture of the pore and thus the flux of molecules between cells. During pathogen infection, plant cells initiate a range of immune responses and it was recently identified that, following perception of fungal and bacterial pathogens, plant cells initially close their PD. Systemic defence responses depend on the spread of signals between cells, raising questions about whether PD are in different functional states during different immune responses. It is well established that viral pathogens exploit PD to spread between cells, but it has more recently been identified that protein effectors secreted by fungal pathogens can spread between host cells via PD. It is possible that many classes of pathogens specifically target PD to aid infection, which would infer antagonistic regulation of PD by host and pathogen. How PD regulation benefits both host immune responses and pathogen infection is an important question and demands that we examine the multicellular nature of plant-pathogen interactions. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Interplay between the gut microbiota and immune responses of ayu (Plecoglossus altivelis) during Vibrio anguillarum infection.

PubMed

Nie, Li; Zhou, Qian-Jin; Qiao, Yan; Chen, Jiong

2017-09-01

Gut microbiota plays fundamental roles in protection against pathogen invasion. However, the mechanism and extent of responses of gut microbiota to pathogenic infection are poorly understood. This study investigated the gut bacterial communities and immune responses of ayu (Plecoglossus altivelis) upon exposure to Vibrio anguillarum. The succession of V. anguillarum infection was evidenced by increased expression of immune genes and bacterial loads in ayu tissues, which in turn altered the composition and predicted functions of gut bacterial community. The dynamics of gut bacterial diversity and evenness were temporally stable in control ayu but were reduced in infected subjects, particularly at the late stages of infection. Variations in the gut microbiota were significantly associated with the expression levels of TNF-α (P = 0.019) and IL-1 β (P = 0.013). The profiles of certain gut bacterial taxa were indicative of V. anguillarum infection. Compared with healthy controls, the ayu infected with V. anguillarum possessed less complex, fewer connected, and lower cooperative gut bacterial interspecies interaction, coinciding with significant shifts in keystone species. These findings imply that V. anguillarum infection substantially disrupted the compositions and interspecies interaction of ayu gut bacterial community, thereby altering gut microbial-mediated functions and inducing host immune responses. This study provides an integrated overview on the interaction between the gut microbiota and host immune responses to pathogen infection from an ecological perspective. Copyright © 2017 Elsevier Ltd. All rights reserved.

Entomopathogenic Fungi: New Insights into Host-Pathogen Interactions.

PubMed

Butt, T M; Coates, C J; Dubovskiy, I M; Ratcliffe, N A

2016-01-01

Although many insects successfully live in dangerous environments exposed to diverse communities of microbes, they are often exploited and killed by specialist pathogens. Studies of host-pathogen interactions (HPI) provide valuable insights into the dynamics of the highly aggressive coevolutionary arms race between entomopathogenic fungi (EPF) and their arthropod hosts. The host defenses are designed to exclude the pathogen or mitigate the damage inflicted while the pathogen responds with immune evasion and utilization of host resources. EPF neutralize their immediate surroundings on the insect integument and benefit from the physiochemical properties of the cuticle and its compounds that exclude competing microbes. EPF also exhibit adaptations aimed at minimizing trauma that can be deleterious to both host and pathogen (eg, melanization of hemolymph), form narrow penetration pegs that alleviate host dehydration and produce blastospores that lack immunogenic sugars/enzymes but facilitate rapid assimilation of hemolymph nutrients. In response, insects deploy an extensive armory of hemocytes and macromolecules, such as lectins and phenoloxidase, that repel, immobilize, and kill EPF. New evidence suggests that immune bioactives work synergistically (eg, lysozyme with antimicrobial peptides) to combat infections. Some proteins, including transferrin and apolipophorin III, also demonstrate multifunctional properties, participating in metabolism, homeostasis, and pathogen recognition. This review discusses the molecular intricacies of these HPI, highlighting the interplay between immunity, stress management, and metabolism. Increased knowledge in this area could enhance the efficacy of EPF, ensuring their future in integrated pest management programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Dynamics of delayed pathogen infection models with pathogenic and cellular infections and immune impairment

NASA Astrophysics Data System (ADS)

Elaiw, A. M.; Raezah, A. A.; Alofi, B. S.

2018-02-01

We study the global dynamics of delayed pathogen infection models with immune impairment. Both pathogen-to-susceptible and infected-to-susceptible transmissions have been considered. Bilinear and saturated incidence rates are considered in the first and second model, respectively. We drive the basic reproduction parameter R0 which determines the global dynamics of models. Using Lyapunov method, we established the global stability of the models' steady states. The theoretical results are confirmed by numerical simulations.

The Effect of Ongoing Exposure Dynamics in Dose Response Relationships

PubMed Central

Pujol, Josep M.; Eisenberg, Joseph E.; Haas, Charles N.; Koopman, James S.

2009-01-01

Characterizing infectivity as a function of pathogen dose is integral to microbial risk assessment. Dose-response experiments usually administer doses to subjects at one time. Phenomenological models of the resulting data, such as the exponential and the Beta-Poisson models, ignore dose timing and assume independent risks from each pathogen. Real world exposure to pathogens, however, is a sequence of discrete events where concurrent or prior pathogen arrival affects the capacity of immune effectors to engage and kill newly arriving pathogens. We model immune effector and pathogen interactions during the period before infection becomes established in order to capture the dynamics generating dose timing effects. Model analysis reveals an inverse relationship between the time over which exposures accumulate and the risk of infection. Data from one time dose experiments will thus overestimate per pathogen infection risks of real world exposures. For instance, fitting our model to one time dosing data reveals a risk of 0.66 from 313 Cryptosporidium parvum pathogens. When the temporal exposure window is increased 100-fold using the same parameters fitted by our model to the one time dose data, the risk of infection is reduced to 0.09. Confirmation of this risk prediction requires data from experiments administering doses with different timings. Our model demonstrates that dose timing could markedly alter the risks generated by airborne versus fomite transmitted pathogens. PMID:19503605

Fungal disease dynamics in insect societies: optimal killing rates and the ambivalent effect of high social interaction rates.

PubMed

Novak, Sebastian; Cremer, Sylvia

2015-05-07

Entomopathogenic fungi are potent biocontrol agents that are widely used against insect pests, many of which are social insects. Nevertheless, theoretical investigations of their particular life history are scarce. We develop a model that takes into account the main distinguishing features between traditionally studied diseases and obligate killing pathogens, like the (biocontrol-relevant) insect-pathogenic fungi Metarhizium and Beauveria. First, obligate killing entomopathogenic fungi produce new infectious particles (conidiospores) only after host death and not yet on the living host. Second, the killing rates of entomopathogenic fungi depend strongly on the initial exposure dosage, thus we explicitly consider the pathogen load of individual hosts. Further, we make the model applicable not only to solitary host species, but also to group living species by incorporating social interactions between hosts, like the collective disease defences of insect societies. Our results identify the optimal killing rate for the pathogen that minimises its invasion threshold. Furthermore, we find that the rate of contact between hosts has an ambivalent effect: dense interaction networks between individuals are considered to facilitate disease outbreaks because of increased pathogen transmission. In social insects, this is compensated by their collective disease defences, i.e., social immunity. For the type of pathogens considered here, we show that even without social immunity, high contact rates between live individuals dilute the pathogen in the host colony and hence can reduce individual pathogen loads below disease-causing levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Strategies for new and improved vaccines against ticks and tick-borne diseases.

PubMed

de la Fuente, J; Kopáček, P; Lew-Tabor, A; Maritz-Olivier, C

2016-12-01

Ticks infest a variety of animal species and transmit pathogens causing disease in both humans and animals worldwide. Tick-host-pathogen interactions have evolved through dynamic processes that accommodated the genetic traits of the hosts, pathogens transmitted and the vector tick species that mediate their development and survival. New approaches for tick control are dependent on defining molecular interactions between hosts, ticks and pathogens to allow for discovery of key molecules that could be tested in vaccines or new generation therapeutics for intervention of tick-pathogen cycles. Currently, tick vaccines constitute an effective and environmentally sound approach for the control of ticks and the transmission of the associated tick-borne diseases. New candidate protective antigens will most likely be identified by focusing on proteins with relevant biological function in the feeding, reproduction, development, immune response, subversion of host immunity of the tick vector and/or molecules vital for pathogen infection and transmission. This review addresses different approaches and strategies used for the discovery of protective antigens, including focusing on relevant tick biological functions and proteins, reverse genetics, vaccinomics and tick protein evolution and interactomics. New and improved tick vaccines will most likely contain multiple antigens to control tick infestations and pathogen infection and transmission. © 2016 John Wiley & Sons Ltd.

Co-infection does not predict disease signs in Gopherus tortoises

PubMed Central

Gov, Ryan; Sandmeier, Franziska C.; Snyder, Sarah J.; Tracy, C. Richard

2017-01-01

In disease ecology, the host immune system interacts with environmental conditions and pathogen properties to affect the impact of disease on the host. Within the host, pathogens may interact to facilitate or inhibit each other's growth, and pathogens interact with different hosts differently. We investigated co-infection of two Mycoplasma and the association of infection with clinical signs of upper respiratory tract disease in four congeneric tortoise host species (Gopherus) in the United States to detect differences in infection risk and disease dynamics in these hosts. Mojave Desert tortoises had greater prevalence of Mycoplasma agassizii than Texas tortoises and gopher tortoises, while there were no differences in Mycoplasma testudineum prevalence among host species. In some host species, the presence of each pathogen influenced the infection intensity of the other; hence, these two mycoplasmas interact differently within different hosts, and our results may indicate facilitation of these bacteria. Neither infection nor co-infection was associated with clinical signs of disease, which tend to fluctuate across time. From M. agassizii DNA sequences, we detected no meaningful differentiation of haplotypes among hosts. Experimental inoculation studies and recurrent resampling of wild individuals could help to decipher the underlying mechanisms of disease dynamics in this system. PMID:29134096

Secondary metabolites in plant innate immunity: conserved function of divergent chemicals.

PubMed

Piasecka, Anna; Jedrzejczak-Rey, Nicolas; Bednarek, Paweł

2015-05-01

Plant secondary metabolites carry out numerous functions in interactions between plants and a broad range of other organisms. Experimental evidence strongly supports the indispensable contribution of many constitutive and pathogen-inducible phytochemicals to plant innate immunity. Extensive studies on model plant species, particularly Arabidopsis thaliana, have brought significant advances in our understanding of the molecular mechanisms underpinning pathogen-triggered biosynthesis and activation of defensive secondary metabolites. However, despite the proven significance of secondary metabolites in plant response to pathogenic microorganisms, little is known about the precise mechanisms underlying their contribution to plant immunity. This insufficiency concerns information on the dynamics of cellular and subcellular localization of defensive phytochemicals during the encounters with microbial pathogens and precise knowledge on their mode of action. As many secondary metabolites are characterized by their in vitro antimicrobial activity, these compounds were commonly considered to function in plant defense as in planta antibiotics. Strikingly, recent experimental evidence suggests that at least some of these compounds alternatively may be involved in controlling several immune responses that are evolutionarily conserved in the plant kingdom, including callose deposition and programmed cell death. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Commensal–dendritic-cell interaction specifies a unique protective skin immune signature

PubMed Central

Naik, Shruti; Bouladoux, Nicolas; Linehan, Jonathan L.; Han, Seong-Ji; Harrison, Oliver J.; Wilhelm, Christoph; Conlan, Sean; Himmelfarb, Sarah; Byrd, Allyson L.; Deming, Clayton; Quinones, Mariam; Brenchley, Jason M.; Kong, Heidi H.; Tussiwand, Roxanne; Murphy, Kenneth M.; Merad, Miriam; Segre, Julia A; Belkaid, Yasmine

2015-01-01

The skin represents the primary interface between the host and the environment. This organ is also home to trillions of microorganisms that play an important role in tissue homeostasis and local immunity1–4. Skin microbial communities are highly diverse and can be remodelled over time or in response to environmental challenges5–7. How, in the context of this complexity, individual commensal microorganisms may differentially modulate skin immunity and the consequences of these responses for tissue physiology remains unclear. Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification. In particular, colonization with Staphylococcus epidermidis induces IL-17A+ CD8+ T cells that home to the epidermis, enhance innate barrier immunity and limit pathogen invasion. Commensal-specific T-cell responses result from the coordinated action of skin-resident dendritic cell subsets and are not associated with inflammation, revealing that tissue-resident cells are poised to sense and respond to alterations in microbial communities. This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies. PMID:25539086

Post-translational regulation of plant immunity.

PubMed

Withers, John; Dong, Xinnian

2017-08-01

Plants have evolved multi-layered molecular defense strategies to protect against pathogens. Plant immune signaling largely relies on post-translational modifications (PTMs) to induce rapid alterations of signaling pathways to achieve a response that is appropriate to the type of pathogen and infection pressure. In host cells, dynamic PTMs have emerged as powerful regulatory mechanisms that cells use to adjust their immune response. PTM is also a virulence strategy used by pathogens to subvert host immunity through the activities of effector proteins secreted into the host cell. Recent studies focusing on deciphering post-translational mechanisms underlying plant immunity have offered an in-depth view of how PTMs facilitate efficient immune responses and have provided a more dynamic and holistic view of plant immunity. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Identification of infection- and defense-related genes via a dynamic host-pathogen interaction network using a Candida albicans-zebrafish infection model.

PubMed

Kuo, Zong-Yu; Chuang, Yung-Jen; Chao, Chun-Cheih; Liu, Fu-Chen; Lan, Chung-Yu; Chen, Bor-Sen

2013-01-01

Candida albicans infections and candidiasis are difficult to treat and create very serious therapeutic challenges. In this study, based on interactive time profile microarray data of C. albicans and zebrafish during infection, the infection-related protein-protein interaction (PPI) networks of the two species and the intercellular PPI network between host and pathogen were simultaneously constructed by a dynamic interaction model, modeled as an integrated network consisting of intercellular invasion and cellular defense processes during infection. The signal transduction pathways in regulating morphogenesis and hyphal growth of C. albicans were further investigated based on significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins from which we can gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. The hyphal growth PPI network, zebrafish PPI network and host-pathogen intercellular PPI network were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host, and may help improve medical therapies and facilitate the development of new antifungal drugs. Copyright © 2013 S. Karger AG, Basel.

Loss of competition in the outside host environment generates outbreaks of environmental opportunist pathogens.

PubMed

Anttila, Jani; Ruokolainen, Lasse; Kaitala, Veijo; Laakso, Jouni

2013-01-01

Environmentally transmitted pathogens face ecological interactions (e.g., competition, predation, parasitism) in the outside-host environment and host immune system during infection. Despite the ubiquitousness of environmental opportunist pathogens, traditional epidemiology focuses on obligatory pathogens incapable of environmental growth. Here we ask how competitive interactions in the outside-host environment affect the dynamics of an opportunist pathogen. We present a model coupling the classical SI and Lotka-Volterra competition models. In this model we compare a linear infectivity response and a sigmoidal infectivity response. An important assumption is that pathogen virulence is traded off with competitive ability in the environment. Removing this trade-off easily results in host extinction. The sigmoidal response is associated with catastrophic appearances of disease outbreaks when outside-host species richness, or overall competition pressure, decreases. This indicates that alleviating outside-host competition with antibacterial substances that also target the competitors can have unexpected outcomes by providing benefits for opportunist pathogens. These findings may help in developing alternative ways of controlling environmental opportunist pathogens.

Plant Microbe Interactions in Post Genomic Era: Perspectives and Applications

PubMed Central

Imam, Jahangir; Singh, Puneet K.; Shukla, Pratyoosh

2016-01-01

Deciphering plant–microbe interactions is a promising aspect to understand the benefits and the pathogenic effect of microbes and crop improvement. The advancement in sequencing technologies and various ‘omics’ tool has impressively accelerated the research in biological sciences in this area. The recent and ongoing developments provide a unique approach to describing these intricate interactions and test hypotheses. In the present review, we discuss the role of plant-pathogen interaction in crop improvement. The plant innate immunity has always been an important aspect of research and leads to some interesting information like the adaptation of unique immune mechanisms of plants against pathogens. The development of new techniques in the post - genomic era has greatly enhanced our understanding of the regulation of plant defense mechanisms against pathogens. The present review also provides an overview of beneficial plant–microbe interactions with special reference to Agrobacterium tumefaciens-plant interactions where plant derived signal molecules and plant immune responses are important in pathogenicity and transformation efficiency. The construction of various Genome-scale metabolic models of microorganisms and plants presented a better understanding of all metabolic interactions activated during the interactions. This review also lists the emerging repertoire of phytopathogens and its impact on plant disease resistance. Outline of different aspects of plant-pathogen interactions is presented in this review to bridge the gap between plant microbial ecology and their immune responses. PMID:27725809

Use of an optical trap for study of host-pathogen interactions for dynamic live cell imaging.

PubMed

Tam, Jenny M; Castro, Carlos E; Heath, Robert J W; Mansour, Michael K; Cardenas, Michael L; Xavier, Ramnik J; Lang, Matthew J; Vyas, Jatin M

2011-07-28

Dynamic live cell imaging allows direct visualization of real-time interactions between cells of the immune system(1, 2); however, the lack of spatial and temporal control between the phagocytic cell and microbe has rendered focused observations into the initial interactions of host response to pathogens difficult. Historically, intercellular contact events such as phagocytosis(3) have been imaged by mixing two cell types, and then continuously scanning the field-of-view to find serendipitous intercellular contacts at the appropriate stage of interaction. The stochastic nature of these events renders this process tedious, and it is difficult to observe early or fleeting events in cell-cell contact by this approach. This method requires finding cell pairs that are on the verge of contact, and observing them until they consummate their contact, or do not. To address these limitations, we use optical trapping as a non-invasive, non-destructive, but fast and effective method to position cells in culture. Optical traps, or optical tweezers, are increasingly utilized in biological research to capture and physically manipulate cells and other micron-sized particles in three dimensions(4). Radiation pressure was first observed and applied to optical tweezer systems in 1970(5, 6), and was first used to control biological specimens in 1987(7). Since then, optical tweezers have matured into a technology to probe a variety of biological phenomena(8-13). We describe a method(14) that advances live cell imaging by integrating an optical trap with spinning disk confocal microscopy with temperature and humidity control to provide exquisite spatial and temporal control of pathogenic organisms in a physiological environment to facilitate interactions with host cells, as determined by the operator. Live, pathogenic organisms like Candida albicans and Aspergillus fumigatus, which can cause potentially lethal, invasive infections in immunocompromised individuals(15, 16) (e.g. AIDS, chemotherapy, and organ transplantation patients), were optically trapped using non-destructive laser intensities and moved adjacent to macrophages, which can phagocytose the pathogen. High resolution, transmitted light and fluorescence-based movies established the ability to observe early events of phagocytosis in living cells. To demonstrate the broad applicability in immunology, primary T-cells were also trapped and manipulated to form synapses with anti-CD3 coated microspheres in vivo, and time-lapse imaging of synapse formation was also obtained. By providing a method to exert fine spatial control of live pathogens with respect to immune cells, cellular interactions can be captured by fluorescence microscopy with minimal perturbation to cells and can yield powerful insight into early responses of innate and adaptive immunity.

Genetics of immune recognition and response in Drosophila host defense.

PubMed

Ligoxygakis, Petros

2013-01-01

Due to the evolutionary conservation of innate immune mechanisms, Drosophila has been extensively used as a model for the dissection in genetic terms of innate host immunity to infection. Genetic screening in fruit flies has set the stage for the pathways and systems required for responding to immune challenge and the dynamics of the progression of bacterial and fungal infection. In addition, fruit flies have been used as infection models to dissect host-pathogen interactions from both sides of this equation. This chapter describes our current understanding of the genetics of the fruit fly immune response and summarizes the most important findings in this area during the past decade. © 2013 Elsevier Inc. All rights reserved.

Plant immunity: towards an integrated view of plant-pathogen interactions.

PubMed

Dodds, Peter N; Rathjen, John P

2010-08-01

Plants are engaged in a continuous co-evolutionary struggle for dominance with their pathogens. The outcomes of these interactions are of particular importance to human activities, as they can have dramatic effects on agricultural systems. The recent convergence of molecular studies of plant immunity and pathogen infection strategies is revealing an integrated picture of the plant-pathogen interaction from the perspective of both organisms. Plants have an amazing capacity to recognize pathogens through strategies involving both conserved and variable pathogen elicitors, and pathogens manipulate the defence response through secretion of virulence effector molecules. These insights suggest novel biotechnological approaches to crop protection.

Fungal Iron Availability during Deep Seated Candidiasis Is Defined by a Complex Interplay Involving Systemic and Local Events

PubMed Central

Potrykus, Joanna; Stead, David; MacCallum, Donna M.; Urgast, Dagmar S.; Raab, Andrea; van Rooijen, Nico; Feldmann, Jörg; Brown, Alistair J. P.

2013-01-01

Nutritional immunity – the withholding of nutrients by the host – has long been recognised as an important factor that shapes bacterial-host interactions. However, the dynamics of nutrient availability within local host niches during fungal infection are poorly defined. We have combined laser ablation-inductively coupled plasma mass spectrometry (LA-ICP MS), MALDI imaging and immunohistochemistry with microtranscriptomics to examine iron homeostasis in the host and pathogen in the murine model of systemic candidiasis. Dramatic changes in the renal iron landscape occur during disease progression. The infection perturbs global iron homeostasis in the host leading to iron accumulation in the renal medulla. Paradoxically, this is accompanied by nutritional immunity in the renal cortex as iron exclusion zones emerge locally around fungal lesions. These exclusion zones correlate with immune infiltrates and haem oxygenase 1-expressing host cells. This local nutritional immunity decreases iron availability, leading to a switch in iron acquisition mechanisms within mature fungal lesions, as revealed by laser capture microdissection and qRT-PCR analyses. Therefore, a complex interplay of systemic and local events influences iron homeostasis and pathogen-host dynamics during disease progression. PMID:24146619

Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity.

PubMed

Odorizzi, Pamela M; Feeney, Margaret E

2016-10-01

Pregnancy-associated malaria, including placental malaria, causes significant morbidity and mortality worldwide. Recently, it has been suggested that in utero exposure of the fetus to malaria antigens may negatively impact the developing immune system and result in tolerance to malaria. Here, we review our current knowledge of fetal immunity to malaria, focusing on the dynamic interactions between maternal malaria infection, placental development, and the fetal immune system. A better understanding of the long-term impact of in utero malaria exposure on the development of natural immunity to malaria, immune responses to other childhood pathogens, and vaccine immunogenicity is urgently needed. This may guide the implementation of novel chemoprevention strategies during pregnancy and facilitate the push toward malaria vaccines. Published by Elsevier Ltd.

Small RNAs—The Secret Agents in the Plant-Pathogen Interactions

PubMed Central

Weiberg, Arne; Jin, Hailing

2015-01-01

Eukaryotic regulatory small RNAs (sRNAs) that induce RNA interference (RNAi) are involved in a plethora of biological processes, including host immunity and pathogen virulence. In plants, diverse classes of sRNAs contribute to the regulation of host innate immunity. These immune-regulatory sRNAs operate through distinct RNAi pathways that trigger transcriptional or post-transcriptional gene silencing. Similarly, many pathogen-derived sRNAs also regulate pathogen virulence. Remarkably, the influence of regulatory sRNAs is not limited to the individual organism in which they are generated. It can sometimes extend to interacting species from even different kingdoms. There they trigger gene silencing in the interacting organism, a phenomenon called cross-kingdom RNAi. This is exhibited in advanced pathogens and parasites that produce sRNAs to suppress host immunity. Conversely, in host-induced gene silencing (HIGS), diverse plants are engineered to trigger RNAi against pathogens and pests to confer host resistance. Cross-kingdom RNAi opens up a vastly unexplored area of research on mobile sRNAs in the battlefield between hosts and pathogens. PMID:26123395

Intrinsic disorder in pathogen effectors: protein flexibility as an evolutionary hallmark in a molecular arms race.

PubMed

Marín, Macarena; Uversky, Vladimir N; Ott, Thomas

2013-09-01

Effector proteins represent a refined mechanism of bacterial pathogens to overcome plants' innate immune systems. These modular proteins often manipulate host physiology by directly interfering with immune signaling of plant cells. Even if host cells have developed efficient strategies to perceive the presence of pathogenic microbes and to recognize intracellular effector activity, it remains an open question why only few effectors are recognized directly by plant resistance proteins. Based on in-silico genome-wide surveys and a reevaluation of published structural data, we estimated that bacterial effectors of phytopathogens are highly enriched in long-disordered regions (>50 residues). These structurally flexible segments have no secondary structure under physiological conditions but can fold in a stimulus-dependent manner (e.g., during protein-protein interactions). The high abundance of intrinsic disorder in effectors strongly suggests positive evolutionary selection of this structural feature and highlights the dynamic nature of these proteins. We postulate that such structural flexibility may be essential for (1) effector translocation, (2) evasion of the innate immune system, and (3) host function mimicry. The study of these dynamical regions will greatly complement current structural approaches to understand the molecular mechanisms of these proteins and may help in the prediction of new effectors.

Bottom-up modeling approach for the quantitative estimation of parameters in pathogen-host interactions

PubMed Central

Lehnert, Teresa; Timme, Sandra; Pollmächer, Johannes; Hünniger, Kerstin; Kurzai, Oliver; Figge, Marc Thilo

2015-01-01

Opportunistic fungal pathogens can cause bloodstream infection and severe sepsis upon entering the blood stream of the host. The early immune response in human blood comprises the elimination of pathogens by antimicrobial peptides and innate immune cells, such as neutrophils or monocytes. Mathematical modeling is a predictive method to examine these complex processes and to quantify the dynamics of pathogen-host interactions. Since model parameters are often not directly accessible from experiment, their estimation is required by calibrating model predictions with experimental data. Depending on the complexity of the mathematical model, parameter estimation can be associated with excessively high computational costs in terms of run time and memory. We apply a strategy for reliable parameter estimation where different modeling approaches with increasing complexity are used that build on one another. This bottom-up modeling approach is applied to an experimental human whole-blood infection assay for Candida albicans. Aiming for the quantification of the relative impact of different routes of the immune response against this human-pathogenic fungus, we start from a non-spatial state-based model (SBM), because this level of model complexity allows estimating a priori unknown transition rates between various system states by the global optimization method simulated annealing. Building on the non-spatial SBM, an agent-based model (ABM) is implemented that incorporates the migration of interacting cells in three-dimensional space. The ABM takes advantage of estimated parameters from the non-spatial SBM, leading to a decreased dimensionality of the parameter space. This space can be scanned using a local optimization approach, i.e., least-squares error estimation based on an adaptive regular grid search, to predict cell migration parameters that are not accessible in experiment. In the future, spatio-temporal simulations of whole-blood samples may enable timely stratification of sepsis patients by distinguishing hyper-inflammatory from paralytic phases in immune dysregulation. PMID:26150807

Bottom-up modeling approach for the quantitative estimation of parameters in pathogen-host interactions.

PubMed

Lehnert, Teresa; Timme, Sandra; Pollmächer, Johannes; Hünniger, Kerstin; Kurzai, Oliver; Figge, Marc Thilo

2015-01-01

Opportunistic fungal pathogens can cause bloodstream infection and severe sepsis upon entering the blood stream of the host. The early immune response in human blood comprises the elimination of pathogens by antimicrobial peptides and innate immune cells, such as neutrophils or monocytes. Mathematical modeling is a predictive method to examine these complex processes and to quantify the dynamics of pathogen-host interactions. Since model parameters are often not directly accessible from experiment, their estimation is required by calibrating model predictions with experimental data. Depending on the complexity of the mathematical model, parameter estimation can be associated with excessively high computational costs in terms of run time and memory. We apply a strategy for reliable parameter estimation where different modeling approaches with increasing complexity are used that build on one another. This bottom-up modeling approach is applied to an experimental human whole-blood infection assay for Candida albicans. Aiming for the quantification of the relative impact of different routes of the immune response against this human-pathogenic fungus, we start from a non-spatial state-based model (SBM), because this level of model complexity allows estimating a priori unknown transition rates between various system states by the global optimization method simulated annealing. Building on the non-spatial SBM, an agent-based model (ABM) is implemented that incorporates the migration of interacting cells in three-dimensional space. The ABM takes advantage of estimated parameters from the non-spatial SBM, leading to a decreased dimensionality of the parameter space. This space can be scanned using a local optimization approach, i.e., least-squares error estimation based on an adaptive regular grid search, to predict cell migration parameters that are not accessible in experiment. In the future, spatio-temporal simulations of whole-blood samples may enable timely stratification of sepsis patients by distinguishing hyper-inflammatory from paralytic phases in immune dysregulation.

Interactions of Cryptococcus with Dendritic Cells

PubMed Central

Wozniak, Karen L.

2018-01-01

The fungal pathogens Cryptococcus neoformans and Cryptococcus gattii can cause life-threatening infections in immune compromised and immune competent hosts. These pathogens enter the host via inhalation, and respiratory tract innate immune cells such as dendritic cells (DCs) are one of the first host cells they encounter. The interactions between Cryptococcus and innate immune cells play a critical role in the progression of disease in the host. This review will focus specifically on the interactions between Cryptococcus and dendritic cells (DCs), including recognition/processing by DCs, effects of immune mediators on DC recruitment and activity, and the potential for DC vaccination against cryptococcosis. PMID:29543719

Interactions of Cryptococcus with Dendritic Cells.

PubMed

Wozniak, Karen L

2018-03-15

The fungal pathogens Cryptococcus neoformans and Cryptococcus gattii can cause life-threatening infections in immune compromised and immune competent hosts. These pathogens enter the host via inhalation, and respiratory tract innate immune cells such as dendritic cells (DCs) are one of the first host cells they encounter. The interactions between Cryptococcus and innate immune cells play a critical role in the progression of disease in the host. This review will focus specifically on the interactions between Cryptococcus and dendritic cells (DCs), including recognition/processing by DCs, effects of immune mediators on DC recruitment and activity, and the potential for DC vaccination against cryptococcosis.

Immunoadolescence: Neuroimmune development and adolescent behavior

PubMed Central

Brenhouse, Heather C.; Schwarz, Jaclyn M.

2016-01-01

The brain is increasingly appreciated to be a constantly rewired organ that yields age-specific behaviors and responses to the environment. Adolescence in particular is a unique period characterized by continued brain maturation, superimposed with transient needs of the organism to traverse a leap from parental dependence to independence. Here we describe how these needs require immune maturation, as well as brain maturation. Our immune system, which protects us from pathogens and regulates inflammation, is in constant communication with our nervous system. Together, neuro-immune signaling regulates our behavioral responses to the environment, making this interaction a likely substrate for adolescent development. We review here the identified as well as understudied components of neuro-immune interactions during adolescence. Synaptic pruning, neurite outgrowth, and neurotransmitter release during adolescence all regulate—and are regulated by—immune signals, which occur via blood-brain barrier dynamics and glial activity. We discuss these processes, as well as how immune signaling during this transitional period of development confers differential effects on behavior and vulnerability to mental illness. PMID:27260127

Plant-bacterial pathogen interactions mediated by type III effectors.

PubMed

Feng, Feng; Zhou, Jian-Min

2012-08-01

Effectors secreted by the bacterial type III system play a central role in the interaction between Gram-negative bacterial pathogens and their host plants. Recent advances in the effector studies have helped cementing several key concepts concerning bacterial pathogenesis, plant immunity, and plant-pathogen co-evolution. Type III effectors use a variety of biochemical mechanisms to target specific host proteins or DNA for pathogenesis. The identifications of their host targets led to the identification of novel components of plant innate immune system. Key modules of plant immune signaling pathways such as immune receptor complexes and MAPK cascades have emerged as a major battle ground for host-pathogen adaptation. These modules are attacked by multiple type III effectors, and some components of these modules have evolved to actively sense the effectors and trigger immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cytotoxic Killing and Immune Evasion by Repair

NASA Astrophysics Data System (ADS)

Chan, Cliburn; George, Andrew J. T.; Stark, Jaroslav

2007-07-01

The interaction between the immune system and pathogens is a complex one, with pathogens constantly developing new ways of evading destruction by the immune system. The immune system's task is made even harder when the pathogen in question is an intra-cellular one (such as a virus or certain bacteria) and it is necessary to kill the infected host cell in order to eliminate the pathogen. This causes damage to the host, and such killing therefore needs to be carefully controlled, particularly in tissues with poor regenerative potential, or those involved in the immune response itself. Host cells therefore possess repair mechanisms which can counteract killing by immune cells. These in turn can be subverted by pathogens which up-regulate the resistance of infected cells to killing. In this paper, we explore the hypothesis that this repair process plays an important role in determining the efficacy of evasion and escape from immune control. We model a situation where cytotoxic T lymphocytes (CTL) and natural killer (NK) cells kill pathogen-infected and tumour cells by directed secretion of preformed granules containing perforin and granzymes. Resistance to such killing can be conferred by the expression of serine protease inhibitors (serpins). These are utilized by several virally infected and tumour cells, as well as playing a role in the protection of host bystander, immune and immuneprivileged cells. We build a simple stochastic model of cytotoxic killing, where serpins can neutralize granzymes stoichiometrically by forming an irreversible complex, and the survival of the cell is determined by the balance between serpin depletion and replenishment, which in its simplest form is equivalent to the well known shot noise process. We use existing analytical results for this process, and additional simulations to analyse the effects of repair on cytotoxic killing. We then extend the model to the case of a replicating target cell population, which gives a branching process coupled to shot noise. We show how the process of repair can have a major impact on the dynamics of pathogen evasion and escape of tumour cells from immune surveillance

Immune-Neuroendocrine Interactions: Evolution, Ecology, and Susceptibility to Illness.

PubMed

Blom, Johanna M C; Ottaviani, Enzo

2017-11-16

The integration between immune and neuroendocrine systems is crucial for maintaining homeostasis from invertebrates to humans. In the first, the phagocytic cell, i.e., the immunocyte, is the main actor, while in the latter, the principle player is the lymphocyte. Immunocytes are characterized by the presence of pro-opiomelanocortin (POMC) peptides, CRH, and other molecules that display a significant similarity to their mammalian counterparts regarding their functions, as both are mainly involved in fundamental functions such as immune (chemotaxis, phagocytosis, cytotoxicity, etc.) and neuroendocrine (stress) responses. Furthermore, the immune-neuroendocrine system provides vital answers to ecological and immunological demands in terms of economy and efficiency. Finally, susceptibility to disease emerges as the result of a continuous dynamic interaction between the world within and the world outside. New fields such as ecological immunology study the susceptibility to pathogens in an evolutionary perspective while the field of neuro-endocrine-immunology studies the susceptibility from a more immediate perspective.

Interaction of entomopathogenic fungi with the host immune system.

PubMed

Qu, Shuang; Wang, Sibao

2018-06-01

Entomopathogenic fungi can invade wide range of insect hosts in the natural world and have been used as environmentally friendly alternatives to chemical insecticides for pest control. Studies of host-pathogen interactions provide valuable insights into the coevolutionay arms race between fungal pathogens and their hosts. Entomopathogenic fungi have evolved a series of sophisticated strategies to counter insect immune defenses. In response to fungal infection, insect hosts rely on behavior avoidance, physical barrier and innate immune defenses in the fight against invading pathogens. The insect cuticle acts as the first physical barrier against pathogens. It is an inhospitable physiological environment that contains chemicals (e.g., antimicrobial peptides and reactive oxygen species), which inhibit fungal growth. In addition, innate immune responses, including cellular immunity and humoral immunity, play critical roles in preventing fungal infection. In this review, we outline the current state of our knowledge of insect defenses to fungal infection and discuss the strategies by which entomopathogenic fungi counter the host immune system. Increased knowledge regarding the molecular interactions between entomopathogenic fungi and the insect host could provide new strategies for pest management. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dynamic intervention: pathogen disarmament of mitochondrial-based immune surveillance.

PubMed

Holland, Robin L; Blanke, Steven R

2014-11-12

In this issue of Cell Host & Microbe, Suzuki et al. (2014) describe a Vibrio cholerae Type-III-secreted effector that targets mitochondrial dynamics to dampen host innate immune signaling. This suggests that mammalian hosts possess surveillance mechanisms to monitor pathogen-mediated alterations in the integrity of normal cellular processes and organelles. Copyright © 2014 Elsevier Inc. All rights reserved.

Insights From Natural Host-Parasite Interactions: The Drosophila Model

PubMed Central

Keebaugh, Erin S.; Schlenke, Todd A.

2013-01-01

Immune responses against opportunistic pathogens have been extensively studied in Drosophila, leading to a detailed map of the genetics behind innate immunity networks including the Toll, Imd, Jak-Stat, and JNK pathways. However, immune mechanisms of other organisms, particularly plants, have primarily been investigated using natural pathogens. It was the use of natural pathogens in plant research that revealed the plant R/Avr system, a specialized immune response derived from antagonistic coevolution between plant immune proteins and their natural pathogens’ virulence proteins. Thus, we recommend that researchers begin to use natural Drosophila pathogens to identify novel immune mechanisms that may have arisen through antagonistic coevolution with common natural pathogens. In this review, we address the benefits of using natural pathogens in research, describe the known natural pathogens of Drosophila, and discuss exciting prospects for future research on select natural pathogens of Drosophila. PMID:23764256

Evasion and Interactions of the Humoral Innate Immune Response in Pathogen Invasion, Autoimmune Disease, and Cancer

PubMed Central

Rettig, Trisha A.; Harbin, Julie N.; Harrington, Adelaide; Dohmen, Leonie; Fleming, Sherry D.

2015-01-01

The humoral innate immune system is composed of three major branches, complement, coagulation, and natural antibodies. To persist in the host, pathogens, such as bacteria, viruses, and cancers must evade parts of the innate humoral immune system. Disruptions in the humoral innate immune system also play a role in the development of autoimmune diseases. This review will examine how gram positive bacteria, viruses, cancer, and the autoimmune conditions Systemic Lupus Erythematosus and Anti-phospholipid syndrome, interact with these immune system components. Through examining evasion techniques it becomes clear that interplay between these three systems exists. By exploring the interplay and the evasion/disruption of the humoral innate immune system, we can develop a better understanding of pathogenic infections, cancer, and autoimmune disease development. PMID:26145788

Ecophysiology meets conservation: understanding the role of disease in amphibian population declines

PubMed Central

Blaustein, Andrew R.; Gervasi, Stephanie S.; Johnson, Pieter T. J.; Hoverman, Jason T.; Belden, Lisa K.; Bradley, Paul W.; Xie, Gisselle Y.

2012-01-01

Infectious diseases are intimately associated with the dynamics of biodiversity. However, the role that infectious disease plays within ecological communities is complex. The complex effects of infectious disease at the scale of communities and ecosystems are driven by the interaction between host and pathogen. Whether or not a given host–pathogen interaction results in progression from infection to disease is largely dependent on the physiological characteristics of the host within the context of the external environment. Here, we highlight the importance of understanding the outcome of infection and disease in the context of host ecophysiology using amphibians as a model system. Amphibians are ideal for such a discussion because many of their populations are experiencing declines and extinctions, with disease as an important factor implicated in many declines and extinctions. Exposure to pathogens and the host's responses to infection can be influenced by many factors related to physiology such as host life history, immunology, endocrinology, resource acquisition, behaviour and changing climates. In our review, we discuss the relationship between disease and biodiversity. We highlight the dynamics of three amphibian host–pathogen systems that induce different effects on hosts and life stages and illustrate the complexity of amphibian–host–parasite systems. We then review links between environmental stress, endocrine–immune interactions, disease and climate change. PMID:22566676

Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

PubMed

Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

2017-05-01

In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. © 2016 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

The immune response against Candida spp. and Sporothrix schenckii.

PubMed

Martínez-Álvarez, José A; Pérez-García, Luis A; Flores-Carreón, Arturo; Mora-Montes, Héctor M

2014-01-01

Candida albicans is the main causative agent of systemic candidiasis, a condition with high mortality rates. The study of the interaction between C. albicans and immune system components has been thoroughly studied and nowadays there is a model for the anti-C. albicans immune response; however, little is known about the sensing of other pathogenic species of the Candida genus. Sporothrix schenckii is the causative agent of sporotrichosis, a subcutaneous mycosis, and thus far there is limited information about its interaction with the immune system. In this paper, we review the most recent information about the immune sensing of species from genus Candida and S. schenckii. Thoroughly searches in scientific journal databases were performed, looking for papers addressing either Candida- or Sporothrix-immune system interactions. There is a significant advance in the knowledge of non-C. albicans species of Candida and Sporothrix immune sensing; however, there are still relevant points to address, such as the specific contribution of pathogen-associated molecular patterns (PAMPs) for sensing by different immune cells and the immune receptors involved in such interactions. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Innate cell communication kick-starts pathogen-specific immunity

PubMed Central

Rivera, Amariliz; Siracusa, Mark C.; Yap, George S.; Gause, William C.

2016-01-01

Innate cells are responsible for the rapid recognition of infection and mediate essential mechanisms of pathogen elimination, and also facilitate adaptive immune responses. We review here the numerous intricate interactions among innate cells that initiate protective immunity. The efficient eradication of pathogens depends on the coordinated actions of multiple cells, including innate cells and epithelial cells. Rather than acting as isolated effector cells, innate cells are in constant communication with other responding cells of the immune system, locally and distally. These interactions are critically important for the efficient control of primary infections as well for the development of ‘trained’ innate cells that facilitate the rapid elimination of homologous or heterologous infections. PMID:27002843

Membrane microdomains and the cytoskeleton constrain AtHIR1 dynamics and facilitate the formation of an AtHIR1-associated immune complex.

PubMed

Lv, Xueqin; Jing, Yanping; Xiao, Jianwei; Zhang, Yongdeng; Zhu, Yingfang; Julian, Russell; Lin, Jinxing

2017-04-01

Arabidopsis hypersensitive-induced reaction (AtHIR) proteins function in plant innate immunity. However, the underlying mechanisms by which AtHIRs participate in plant immunity remain elusive. Here, using VA-TIRFM and FLIM-FRET, we revealed that AtHIR1 is present in membrane microdomains and co-localizes with the membrane microdomain marker REM1.3. Single-particle tracking analysis revealed that membrane microdomains and the cytoskeleton, especially microtubules, restrict the lateral mobility of AtHIR1 at the plasma membrane and facilitate its oligomerization. Furthermore, protein proximity index measurements, fluorescence cross-correlation spectroscopy, and biochemical experiments demonstrated that the formation of the AtHIR1 complex upon pathogen perception requires intact microdomains and cytoskeleton. Taken together, these findings suggest that microdomains and the cytoskeleton constrain AtHIR1 dynamics, promote AtHIR1 oligomerization, and increase the efficiency of the interactions of AtHIR1 with components of the AtHIR1 complex in response to pathogens, thus providing valuable insight into the mechanisms of defense-related responses in plants. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

No hormone to rule them all: Interactions of plant hormones during the responses of plants to pathogens.

PubMed

Shigenaga, Alexandra M; Argueso, Cristiana T

2016-08-01

Plant hormones are essential regulators of plant growth and immunity. In the last few decades, a vast amount of information has been obtained detailing the role of different plant hormones in immunity, and how they work together to ultimately shape the outcomes of plant pathogen interactions. Here we provide an overview on the roles of the main classes of plant hormones in the regulation of plant immunity, highlighting their metabolic and signaling pathways and how plants and pathogens utilize these pathways to activate or suppress defence. Copyright © 2016 Elsevier Ltd. All rights reserved.

NOD1CARD Might Be Using Multiple Interfaces for RIP2-Mediated CARD-CARD Interaction: Insights from Molecular Dynamics Simulation

PubMed Central

Pradhan, Sukanta Kumar; De, Sachinandan

2017-01-01

The nucleotide-binding and oligomerization domain (NOD)-containing protein 1 (NOD1) plays the pivotal role in host-pathogen interface of innate immunity and triggers immune signalling pathways for the maturation and release of pro-inflammatory cytokines. Upon the recognition of iE-DAP, NOD1 self-oligomerizes in an ATP-dependent fashion and interacts with adaptor molecule receptor-interacting protein 2 (RIP2) for the propagation of innate immune signalling and initiation of pro-inflammatory immune responses. This interaction (mediated by NOD1 and RIP2) helps in transmitting the downstream signals for the activation of NF-κB signalling pathway, and has been arbitrated by respective caspase-recruitment domains (CARDs). The so-called CARD-CARD interaction still remained contradictory due to inconsistent results. Henceforth, to understand the mode and the nature of the interaction, structural bioinformatics approaches were employed. MD simulation of modelled 1:1 heterodimeric complexes revealed that the type-Ia interface of NOD1CARD and the type-Ib interface of RIP2CARD might be the suitable interfaces for the said interaction. Moreover, we perceived three dynamically stable heterotrimeric complexes with an NOD1:RIP2 ratio of 1:2 (two numbers) and 2:1. Out of which, in the first trimeric complex, a type-I NOD1-RIP2 heterodimer was found interacting with an RIP2CARD using their type-IIa and IIIa interfaces. However, in the second and third heterotrimer, we observed type-I homodimers of NOD1 and RIP2 CARDs were interacting individually with RIP2CARD and NOD1CARD (in type-II and type-III interface), respectively. Overall, this study provides structural and dynamic insights into the NOD1-RIP2 oligomer formation, which will be crucial in understanding the molecular basis of NOD1-mediated CARD-CARD interaction in higher and lower eukaryotes. PMID:28114344

Real-time monitoring of immune responses under pathogen invasion and drug interference by integrated microfluidic device coupled with worm-based biosensor.

PubMed

Hu, Liang; Ge, Anle; Wang, Xixian; Wang, Shanshan; Yue, Xinpei; Wang, Jie; Feng, Xiaojun; Du, Wei; Liu, Bi-Feng

2018-07-01

Immune response to environmental pathogen invasion is a complex process to prevent host from further damage. For quantitatively understanding immune responses and revealing the pathogenic environmental information, real-time monitoring of such a whole dynamic process with single-animal resolution in well-defined environments is highly desired. In this work, an integrated microfluidic device coupled with worm-based biosensor was proposed for in vivo studies of dynamic immune responses and antibiotics interference in infected C. elegans. Individual worms housed in chambers were exposed to the various pathogens and discontinuously manipulated for imaging with limited influence on physiological activities. The expression of immune responses gene (irg-1) was time-lapse measured in intact worms during pathogen infection. Results demonstrated that irg-1 gene could be induced in the presence of P. aeruginosa strain PA14 in a dose-dependent manner, and the survival of infected worm could be rescued under gentamicin or erythromycin treatments. We expect it to be a versatile platform to facilitate future studies on pathogenesis researches and rapid drug screen using C. elegans disease model. Copyright © 2018 Elsevier B.V. All rights reserved.

Vaccine development: From concept to early clinical testing.

PubMed

Cunningham, Anthony L; Garçon, Nathalie; Leo, Oberdan; Friedland, Leonard R; Strugnell, Richard; Laupèze, Béatrice; Doherty, Mark; Stern, Peter

2016-12-20

In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response. Processes such as recombinant DNA technology can simplify the complexity of manufacturing and facilitate consistent production of large quantities of antigen. Any new vaccine development is greatly enhanced by, and requires integration of information concerning: 1. Pathogen life-cycle & epidemiology. Knowledge of pathogen structure, route of entry, interaction with cellular receptors, subsequent replication sites and disease-causing mechanisms are all important to identify antigens suitable for disease prevention. The demographics of infection, specific risk groups and age-specific infection rates determine which population to immunise, and at what age. 2. Immune control & escape. Interactions between the host and pathogen are explored, with determination of the relative importance of antibodies, T-cells of different types and innate immunity, immune escape strategies during infection, and possible immune correlates of protection. This information guides identification and selection of antigen and the specific immune response required for protection. 3. Antigen selection & vaccine formulation. The selected antigen is formulated to remain suitably immunogenic and stable over time, induce an immune response that is likely to be protective, plus be amenable to eventual scale-up to commercial production. 4. Vaccine preclinical & clinical testing. The candidate vaccine must be tested for immunogenicity, safety and efficacy in preclinical and appropriately designed clinical trials. This review considers these processes using examples of differing pathogenic challenges, including human papillomavirus, malaria, and ebola. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Bivalve immunity and response to infections: Are we looking at the right place?

PubMed

Allam, Bassem; Pales Espinosa, Emmanuelle

2016-06-01

Significant progress has been made in the understanding of cellular and molecular mediators of immunity in invertebrates in general and bivalve mollusks in particular. Despite this information, there is a lack of understanding of factors affecting animal resistance and specific responses to infections. This in part results from limited consideration of the spatial (and to some extent temporal) heterogeneity of immune responses and very limited information on host-pathogen (and microbes in general) interactions at initial encounter/colonization sites. Of great concern is the fact that most studies on molluscan immunity focus on the circulating hemocytes and the humoral defense factors in the plasma while most relevant host-microbe interactions occur at mucosal interfaces. This paper summarizes information available on the contrasting value of information available on focal and systemic immune responses in infected bivalves, and highlights the role of mucosal immune factors in host-pathogen interactions. Available information underlines the diversity of immune effectors at molluscan mucosal interfaces and highlights the tailored immune response to pathogen stimuli. This context raises fascinating basic research questions around host-microbe crosstalk and feedback controls of these interactions and may lead to novel disease mitigation strategies and improve the assessment of resistant crops or the screening of probiotic candidates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bacterial Serine/Threonine Protein Kinases in Host-Pathogen Interactions*

PubMed Central

Canova, Marc J.; Molle, Virginie

2014-01-01

In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection. PMID:24554701

Bacterial serine/threonine protein kinases in host-pathogen interactions.

PubMed

Canova, Marc J; Molle, Virginie

2014-04-04

In bacterial pathogenesis, monitoring and adapting to the dynamically changing environment in the host and an ability to disrupt host immune responses are critical. The virulence determinants of pathogenic bacteria include the sensor/signaling proteins of the serine/threonine protein kinase (STPK) family that have a dual role of sensing the environment and subverting specific host defense processes. STPKs can sense a wide range of signals and coordinate multiple cellular processes to mount an appropriate response. Here, we review some of the well studied bacterial STPKs that are essential virulence factors and that modify global host responses during infection.

Modeling Systems-Level Regulation of Host Immune Responses

PubMed Central

Thakar, Juilee; Pilione, Mylisa; Kirimanjeswara, Girish; Harvill, Eric T; Albert, Réka

2007-01-01

Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the most active immune processes. We compare and discuss the effect of the species-specific virulence factors on disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the virulence, pathogenesis, and host adaptation of disease-causing microorganisms and allows systems-level analysis that is not always possible using traditional methods. PMID:17559300

Multi-event capture–recapture modeling of host–pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns

PubMed Central

2014-01-01

Host–pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture–recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host–pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

Real-time analysis of Drosophila post-embryonic haemocyte behaviour.

PubMed

Sampson, Christopher J; Williams, Michael J

2012-01-01

The larval stage of the model organism Drosophila is frequently used to study host-pathogen interactions. During embryogenesis the cellular arm of the immune response, consisting of macrophage-like cells known as plasmatocytes, is extremely motile and functions to phagocytise pathogens and apoptotic bodies, as well as produce extracellular matrix. The cellular branch of the larval (post-embryonic) innate immune system consists of three cell types--plasmatocytes, crystal cells and lamellocytes--which are involved in the phagocytosis, encapsulation and melanisation of invading pathogens. Post-embryonic haemocyte motility is poorly understood thus further characterisation is required, for the purpose of standardisation. In order to examine post-embryonic haemocyte cytoskeletal dynamics or migration, the most commonly used system is in vitro cell lines. The current study employs an ex vivo system (an adaptation of in vitro cell incubation using primary cells), in which primary larval or pre-pupal haemocytes are isolated for short term analysis, in order to discover various aspects of their behaviour during events requiring cytoskeleton dynamics. The ex vivo method allows for real-time analysis and manipulation of primary post-embryonic haemocytes. This technique was used to characterise, and potentially standardised, larval and pre-pupal haemocyte cytoskeleton dynamics, assayed on different extracellular matrices. Using this method it was determined that, while larval haemocytes are unable to migrate, haemocytes recovered from pre-pupae are capable of migration.

Expanding the universe of cytokines and pattern recognition receptors: galectins and glycans in innate immunity.

PubMed

Cerliani, Juan P; Stowell, Sean R; Mascanfroni, Iván D; Arthur, Connie M; Cummings, Richard D; Rabinovich, Gabriel A

2011-02-01

Effective immunity relies on the recognition of pathogens and tumors by innate immune cells through diverse pattern recognition receptors (PRRs) that lead to initiation of signaling processes and secretion of pro- and anti-inflammatory cytokines. Galectins, a family of endogenous lectins widely expressed in infected and neoplastic tissues have emerged as part of the portfolio of soluble mediators and pattern recognition receptors responsible for eliciting and controlling innate immunity. These highly conserved glycan-binding proteins can control immune cell processes through binding to specific glycan structures on pathogens and tumors or by acting intracellularly via modulation of selective signaling pathways. Recent findings demonstrate that various galectin family members influence the fate and physiology of different innate immune cells including polymorphonuclear neutrophils, mast cells, macrophages, and dendritic cells. Moreover, several pathogens may actually utilize galectins as a mechanism of host invasion. In this review, we aim to highlight and integrate recent discoveries that have led to our current understanding of the role of galectins in host-pathogen interactions and innate immunity. Challenges for the future will embrace the rational manipulation of galectin-glycan interactions to instruct and shape innate immunity during microbial infections, inflammation, and cancer.

A basic mathematical model of the immune response

NASA Astrophysics Data System (ADS)

Mayer, H.; Zaenker, K. S.; an der Heiden, U.

1995-03-01

Interaction of the immune system with a target population of, e.g., bacteria, viruses, antigens, or tumor cells must be considered as a dynamic process. We describe this process by a system of two ordinary differential equations. Although the model is strongly idealized it demonstrates how the combination of a few proposed nonlinear interaction rules between the immune system and its targets are able to generate a considerable variety of different kinds of immune responses, many of which are observed both experimentally and clinically. In particular, solutions of the model equations correspond to states described by immunologists as ``virgin state,'' ``immune state'' and ``state of tolerance.'' The model successfully replicates the so-called primary and secondary response. Moreover, it predicts the existence of a threshold level for the amount of pathogen germs or of transplanted tumor cells below which the host is able to eliminate the infectious organism or to reject the tumor graft. We also find a long time coexistence of targets and immune competent cells including damped and undamped oscillations of both. Plausibly the model explains that if the number of transformed cells or pathogens exeeds definable values (poor antigenicity, high reproduction rate) the immune system fails to keep the disease under control. On the other hand, the model predicts apparently paradoxical situations including an increased chance of target survival despite enhanced immune activity or therapeutically achieved target reduction. A further obviously paradoxical behavior consists of a positive effect for the patient up to a complete cure by adding an additional target challenge where the benefit of the additional targets depends strongly on the time point and on their amount. Under periodically pulsed stimulation the model may show a chaotic time behavior of both target growth and immune response.

Quasispecies dynamics on a network of interacting genotypes and idiotypes: applications to autoimmunity and immunodeficiency

NASA Astrophysics Data System (ADS)

Barbosa, Valmir C.; Donangelo, Raul; Souza, Sergio R.

2016-06-01

In spite of their many facets, the phenomena of autoimmunity and immunodeficiency seem to be related to each other through the subtle links connecting the mutation and action of retroviruses (viruses whose genetic material can find its way into that of the host’s cells and destroy them) to immune response and adaptation. In a previous work, we introduced a network model of how a set of interrelated genotypes (called a quasispecies, in the stationary state, representing for example a population of viruses) and a set of interrelated idiotypes (an idiotypic network, representing the immune system through its population of B and T cells) interact. That model, which does not cover the case of a retroviral quasispecies, is here extended by the addition of a further parameter (ν) to account for the action of retroviruses (i.e. the destruction of idiotypes by genotypes). We give simulation results within a suitable parameter niche, highlighting the issues of quasispecies survival and of the onset of autoimmunity through the appearance of the so-called pathogenic idiotypes (those that mimic some external pathogen). Our main findings refer to how ν and λ, a parameter describing the rate at which idiotypes get stimulated, relate to each other. While for ν >λ the quasispecies survives at the expense of weakening the immune system significantly or even destroying it, for ν <λ the fittest genotypes of the quasispecies become mimicked inside the immune system as pathogenic idiotypes. The latter is in agreement with the current understanding of the HIV quasispecies.

Effects of Air Pollutants on Innate Immunity: The Role of Toll-like receptors and nucleotide-binding oligomerization domain-like receptors

EPA Science Inventory

Interactions between exposure to ambient air pollutants and respiratory pathogens have been shown to modify respiratory immune responses. Emerging data suggest key roles for toll-like receptor (TLR) and NOD-like receptor (NLR) signaling in pathogen-induced immune responses. Simil...

Anaplasma phagocytophilum MSP4 and HSP70 Proteins Are Involved in Interactions with Host Cells during Pathogen Infection

PubMed Central

Contreras, Marinela; Alberdi, Pilar; Mateos-Hernández, Lourdes; Fernández de Mera, Isabel G.; García-Pérez, Ana L.; Vancová, Marie; Villar, Margarita; Ayllón, Nieves; Cabezas-Cruz, Alejandro; Valdés, James J.; Stuen, Snorre; Gortazar, Christian; de la Fuente, José

2017-01-01

Anaplasma phagocytophilum transmembrane and surface proteins play a role during infection and multiplication in host neutrophils and tick vector cells. Recently, A. phagocytophilum Major surface protein 4 (MSP4) and Heat shock protein 70 (HSP70) were shown to be localized on the bacterial membrane, with a possible role during pathogen infection in ticks. In this study, we hypothesized that A. phagocytophilum MSP4 and HSP70 have similar functions in tick-pathogen and host-pathogen interactions. To address this hypothesis, herein we characterized the role of these bacterial proteins in interaction and infection of vertebrate host cells. The results showed that A. phagocytophilum MSP4 and HSP70 are involved in host-pathogen interactions, with a role for HSP70 during pathogen infection. The analysis of the potential protective capacity of MSP4 and MSP4-HSP70 antigens in immunized sheep showed that MSP4-HSP70 was only partially protective against pathogen infection. This limited protection may be associated with several factors, including the recognition of non-protective epitopes by IgG in immunized lambs. Nevertheless, these antigens may be combined with other candidate protective antigens for the development of vaccines for the control of human and animal granulocytic anaplasmosis. Focusing on the characterization of host protective immune mechanisms and protein-protein interactions at the host-pathogen interface may lead to the discovery and design of new effective protective antigens. PMID:28725639

Anaplasma phagocytophilum MSP4 and HSP70 Proteins Are Involved in Interactions with Host Cells during Pathogen Infection.

PubMed

Contreras, Marinela; Alberdi, Pilar; Mateos-Hernández, Lourdes; Fernández de Mera, Isabel G; García-Pérez, Ana L; Vancová, Marie; Villar, Margarita; Ayllón, Nieves; Cabezas-Cruz, Alejandro; Valdés, James J; Stuen, Snorre; Gortazar, Christian; de la Fuente, José

2017-01-01

Anaplasma phagocytophilum transmembrane and surface proteins play a role during infection and multiplication in host neutrophils and tick vector cells. Recently, A. phagocytophilum Major surface protein 4 (MSP4) and Heat shock protein 70 (HSP70) were shown to be localized on the bacterial membrane, with a possible role during pathogen infection in ticks. In this study, we hypothesized that A. phagocytophilum MSP4 and HSP70 have similar functions in tick-pathogen and host-pathogen interactions. To address this hypothesis, herein we characterized the role of these bacterial proteins in interaction and infection of vertebrate host cells. The results showed that A. phagocytophilum MSP4 and HSP70 are involved in host-pathogen interactions, with a role for HSP70 during pathogen infection. The analysis of the potential protective capacity of MSP4 and MSP4-HSP70 antigens in immunized sheep showed that MSP4-HSP70 was only partially protective against pathogen infection. This limited protection may be associated with several factors, including the recognition of non-protective epitopes by IgG in immunized lambs. Nevertheless, these antigens may be combined with other candidate protective antigens for the development of vaccines for the control of human and animal granulocytic anaplasmosis. Focusing on the characterization of host protective immune mechanisms and protein-protein interactions at the host-pathogen interface may lead to the discovery and design of new effective protective antigens.

Host-microbiota interactions within the fish intestinal ecosystem.

PubMed

Pérez, T; Balcázar, J L; Ruiz-Zarzuela, I; Halaihel, N; Vendrell, D; de Blas, I; Múzquiz, J L

2010-07-01

Teleost fish are in direct contact with the aquatic environment, and are therefore in continual contact with a complex and dynamic microbiota, some of which may have implications for health. Mucosal surfaces represent the main sites in which environmental antigens and intestinal microbiota interact with the host. Thus, the gut-associated lymphoid tissues (GALT) must develop mechanisms to discriminate between pathogenic and commensal microorganisms. Colonization of intestinal mucosal surfaces with a normal microbiota has a positive effect on immune regulatory functions of the gut, and disturbance in these immune regulatory functions by an imbalanced microbiota may contribute to the development of diseases. Significant attention has therefore been recently focused on the role of probiotics in the induction or restoration of a disturbed microbiota to its normal beneficial composition. Given this, this article explores the fascinating relationship between the fish immune system and the bacteria that are present in its intestinal microbiota, focusing on the bacterial effect on the development of certain immune responses.

Experimental evolution of insect immune memory versus pathogen resistance.

PubMed

Khan, Imroze; Prakash, Arun; Agashe, Deepa

2017-12-20

Under strong pathogen pressure, insects often evolve resistance to infection. Many insects are also protected via immune memory (immune priming), whereby sublethal exposure to a pathogen enhances survival after secondary infection. Theory predicts that immune memory should evolve when the pathogen is highly virulent, or when pathogen exposure is relatively rare. However, there are no empirical tests of these hypotheses, and the adaptive benefits of immune memory relative to direct resistance against a pathogen are poorly understood. To determine the selective pressures and ecological conditions that shape immune evolution, we imposed strong pathogen selection on flour beetle ( Tribolium castaneum ) populations, infecting them with Bacillus thuringiensis (Bt) for 11 generations. Populations injected first with heat-killed and then live Bt evolved high basal resistance against multiple Bt strains. By contrast, populations injected only with a high dose of live Bt evolved a less effective but strain-specific priming response. Control populations injected with heat-killed Bt did not evolve priming; and in the ancestor, priming was effective only against a low Bt dose. Intriguingly, one replicate population first evolved priming and subsequently evolved basal resistance, suggesting the potential for dynamic evolution of different immune strategies. Our work is the first report showing that pathogens can select for rapid modulation of insect priming ability, allowing hosts to evolve divergent immune strategies (generalized resistance versus specific immune memory) with potentially distinct mechanisms. © 2017 The Author(s).

Glycomaterials for probing host–pathogen interactions and the immune response

PubMed Central

Huang, Mia L; Fisher, Christopher J

2016-01-01

The initial engagement of host cells by pathogens is often mediated by glycan structures presented on the cell surface. Various components of the glycocalyx can be targeted by pathogens for adhesion to facilitate infection. Glycans also play integral roles in the modulation of the host immune response to infection. Therefore, understanding the parameters that define glycan interactions with both pathogens and the various components of the host immune system can aid in the development of strategies to prevent, interrupt, or manage infection. Glycomaterials provide a unique and powerful tool with which to interrogate the compositional and functional complexity of the glycocalyx. The objective of this review is to highlight some key contributions from this area of research in deciphering the mechanisms of pathogenesis and the associated host response. PMID:27190259

Two-Component Elements Mediate Interactions between Cytokinin and Salicylic Acid in Plant Immunity

PubMed Central

Argueso, Cristiana T.; Ferreira, Fernando J.; Epple, Petra; To, Jennifer P. C.; Hutchison, Claire E.; Schaller, G. Eric; Dangl, Jeffery L.; Kieber, Joseph J.

2012-01-01

Recent studies have revealed an important role for hormones in plant immunity. We are now beginning to understand the contribution of crosstalk among different hormone signaling networks to the outcome of plant–pathogen interactions. Cytokinins are plant hormones that regulate development and responses to the environment. Cytokinin signaling involves a phosphorelay circuitry similar to two-component systems used by bacteria and fungi to perceive and react to various environmental stimuli. In this study, we asked whether cytokinin and components of cytokinin signaling contribute to plant immunity. We demonstrate that cytokinin levels in Arabidopsis are important in determining the amplitude of immune responses, ultimately influencing the outcome of plant–pathogen interactions. We show that high concentrations of cytokinin lead to increased defense responses to a virulent oomycete pathogen, through a process that is dependent on salicylic acid (SA) accumulation and activation of defense gene expression. Surprisingly, treatment with lower concentrations of cytokinin results in increased susceptibility. These functions for cytokinin in plant immunity require a host phosphorelay system and are mediated in part by type-A response regulators, which act as negative regulators of basal and pathogen-induced SA–dependent gene expression. Our results support a model in which cytokinin up-regulates plant immunity via an elevation of SA–dependent defense responses and in which SA in turn feedback-inhibits cytokinin signaling. The crosstalk between cytokinin and SA signaling networks may help plants fine-tune defense responses against pathogens. PMID:22291601

[Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment].

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2016-01-01

Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

Pattern Recognition Receptors in Innate Immunity, Host Defense, and Immunopathology

ERIC Educational Resources Information Center

Suresh, Rahul; Mosser, David M.

2013-01-01

Infection by pathogenic microbes initiates a set of complex interactions between the pathogen and the host mediated by pattern recognition receptors. Innate immune responses play direct roles in host defense during the early stages of infection, and they also exert a profound influence on the generation of the adaptive immune responses that ensue.…

Agent-based modeling approach of immune defense against spores of opportunistic human pathogenic fungi.

PubMed

Tokarski, Christian; Hummert, Sabine; Mech, Franziska; Figge, Marc Thilo; Germerodt, Sebastian; Schroeter, Anja; Schuster, Stefan

2012-01-01

Opportunistic human pathogenic fungi like the ubiquitous fungus Aspergillus fumigatus are a major threat to immunocompromised patients. An impaired immune system renders the body vulnerable to invasive mycoses that often lead to the death of the patient. While the number of immunocompromised patients is rising with medical progress, the process, and dynamics of defense against invaded and ready to germinate fungal conidia are still insufficiently understood. Besides macrophages, neutrophil granulocytes form an important line of defense in that they clear conidia. Live imaging shows the interaction of those phagocytes and conidia as a dynamic process of touching, dragging, and phagocytosis. To unravel strategies of phagocytes on the hunt for conidia an agent-based modeling approach is used, implemented in NetLogo. Different modes of movement of phagocytes are tested regarding their clearing efficiency: random walk, short-term persistence in their recent direction, chemotaxis of chemokines excreted by conidia, and communication between phagocytes. While the short-term persistence hunting strategy turned out to be superior to the simple random walk, following a gradient of chemokines released by conidial agents is even better. The advantage of communication between neutrophilic agents showed a strong dependency on the spatial scale of the focused area and the distribution of the pathogens.

Predation on multiple trophic levels shapes the evolution of pathogen virulence.

PubMed

Friman, Ville-Petri; Lindstedt, Carita; Hiltunen, Teppo; Laakso, Jouni; Mappes, Johanna

2009-08-25

The pathogen virulence is traditionally thought to co-evolve as a result of reciprocal selection with its host organism. In natural communities, pathogens and hosts are typically embedded within a web of interactions with other species, which could affect indirectly the pathogen virulence and host immunity through trade-offs. Here we show that selection by predation can affect both pathogen virulence and host immune defence. Exposing opportunistic bacterial pathogen Serratia marcescens to predation by protozoan Tetrahymena thermophila decreased its virulence when measured as host moth Parasemia plantaginis survival. This was probably because the bacterial anti-predatory traits were traded off with bacterial virulence factors, such as motility or resource use efficiency. However, the host survival depended also on its allocation to warning signal that is used against avian predation. When infected with most virulent ancestral bacterial strain, host larvae with a small warning signal survived better than those with an effective large signal. This suggests that larval immune defence could be traded off with effective defence against bird predators. However, the signal size had no effect on larval survival when less virulent control or evolved strains were used for infection suggesting that anti-predatory defence against avian predators, might be less constrained when the invading pathogen is rather low in virulence. Our results demonstrate that predation can be important indirect driver of the evolution of both pathogen virulence and host immunity in communities with multiple species interactions. Thus, the pathogen virulence should be viewed as a result of both past evolutionary history, and current ecological interactions.

Update on host-pathogen interactions in cystic fibrosis lung disease.

PubMed

Hector, Andreas; Frey, Nina; Hartl, Dominik

2016-12-01

Bacterial and fungal infections are hallmarks of cystic fibrosis (CF) lung disease. In the era of long-term inhaled antibiotics and increasing CF patient survival, new "emerging" pathogens are detected in CF airways, yet their pathophysiological disease relevance remains largely controversial and incompletely defined. As a response to chronic microbial triggers, innate immune cells, particularly neutrophils, are continuously recruited into CF airways where they combat pathogens but also cause tissue injury through release of oxidants and proteases. The coordinated interplay between host immune cell activation and pathogens is essential for the outcome of CF lung disease. Here, we provide a concise overview and update on host-pathogen interactions in CF lung disease.

Proteomics and plant disease: advances in combating a major threat to the global food supply.

PubMed

Rampitsch, Christof; Bykova, Natalia V

2012-02-01

The study of plant disease and immunity is benefiting tremendously from proteomics. Parallel streams of research from model systems, from pathogens in vitro and from the relevant pathogen-crop interactions themselves have begun to reveal a model of how plants succumb to invading pathogens and how they defend themselves without the benefit of a circulating immune system. In this review, we discuss the contribution of proteomics to these advances, drawing mainly on examples from crop-fungus interactions, from Arabidopsis-bacteria interactions, from elicitor-based model systems and from pathogen studies, to highlight also the important contribution of non-crop systems to advancing crop protection. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interacting Symbionts and Immunity in the Amphibian Skin Mucosome Predict Disease Risk and Probiotic Effectiveness

PubMed Central

Woodhams, Douglas C.; Brandt, Hannelore; Baumgartner, Simone; Kielgast, Jos; Küpfer, Eliane; Tobler, Ursina; Davis, Leyla R.; Schmidt, Benedikt R.; Bel, Christian; Hodel, Sandro; Knight, Rob; McKenzie, Valerie

2014-01-01

Pathogenesis is strongly dependent on microbial context, but development of probiotic therapies has neglected the impact of ecological interactions. Dynamics among microbial communities, host immune responses, and environmental conditions may alter the effect of probiotics in human and veterinary medicine, agriculture and aquaculture, and the proposed treatment of emerging wildlife and zoonotic diseases such as those occurring on amphibians or vectored by mosquitoes. Here we use a holistic measure of amphibian mucosal defenses to test the effects of probiotic treatments and to assess disease risk under different ecological contexts. We developed a non-invasive assay for antifungal function of the skin mucosal ecosystem (mucosome function) integrating host immune factors and the microbial community as an alternative to pathogen exposure experiments. From approximately 8500 amphibians sampled across Europe, we compared field infection prevalence with mucosome function against the emerging fungal pathogen Batrachochytrium dendrobatidis. Four species were tested with laboratory exposure experiments, and a highly susceptible species, Alytes obstetricans, was treated with a variety of temperature and microbial conditions to test the effects of probiotic therapies and environmental conditions on mucosome function. We found that antifungal function of the amphibian skin mucosome predicts the prevalence of infection with the fungal pathogen in natural populations, and is linked to survival in laboratory exposure experiments. When altered by probiotic therapy, the mucosome increased antifungal capacity, while previous exposure to the pathogen was suppressive. In culture, antifungal properties of probiotics depended strongly on immunological and environmental context including temperature, competition, and pathogen presence. Functional changes in microbiota with shifts in temperature provide an alternative mechanistic explanation for patterns of disease susceptibility related to climate beyond direct impact on host or pathogen. This nonlethal management tool can be used to optimize and quickly assess the relative benefits of probiotic therapies under different climatic, microbial, or host conditions. PMID:24789229

Commensal microbiome effects on mucosal immune system development in the ruminant gastrointestinal tract.

PubMed

Taschuk, Ryan; Griebel, Philip J

2012-06-01

Commensal microflora play many roles within the mammalian gastrointestinal tract (GIT) that benefit host physiology by way of direct or indirect interactions with mucosal surfaces. Commensal flora comprises members across all microbial phyla, although predominantly bacterial, with population dynamics varying with host species, genotype, and environmental factors. Little is known, however, about the complex mechanisms regulating host-commensal interactions that underlie this mutually beneficial relationship and how alterations in the microbiome may influence host development and susceptibility to infection. Research into the gut microbiome has intensified as it becomes increasingly evident that symbiont-host interactions have a significant impact on mucosal immunity and health. Furthermore, evidence that microbial populations vary significantly throughout the GIT suggest that regional differences in the microbiome may also influence immune function within distinct compartments of the GIT. Postpartum colonization of the GIT has been shown to have a direct effect on mucosal immune system development, but information is limited regarding regional effects of the microbiome on the development, activation, and maturation of the mucosal immune system. This review discusses factors influencing the colonization and establishment of the microbiome throughout the GIT of newborn calves and the evidence that regional differences in the microbiome influence mucosal immune system development and maturation. The implications of this complex interaction are also discussed in terms of possible effects on responses to enteric pathogens and vaccines.

A Virtual Infection Model Quantifies Innate Effector Mechanisms and Candida albicans Immune Escape in Human Blood

PubMed Central

Bieber, Kristin; Martin, Ronny; Figge, Marc Thilo; Kurzai, Oliver

2014-01-01

Candida albicans bloodstream infection is increasingly frequent and can result in disseminated candidiasis associated with high mortality rates. To analyze the innate immune response against C. albicans, fungal cells were added to human whole-blood samples. After inoculation, C. albicans started to filament and predominantly associate with neutrophils, whereas only a minority of fungal cells became attached to monocytes. While many parameters of host-pathogen interaction were accessible to direct experimental quantification in the whole-blood infection assay, others were not. To overcome these limitations, we generated a virtual infection model that allowed detailed and quantitative predictions on the dynamics of host-pathogen interaction. Experimental time-resolved data were simulated using a state-based modeling approach combined with the Monte Carlo method of simulated annealing to obtain quantitative predictions on a priori unknown transition rates and to identify the main axis of antifungal immunity. Results clearly demonstrated a predominant role of neutrophils, mediated by phagocytosis and intracellular killing as well as the release of antifungal effector molecules upon activation, resulting in extracellular fungicidal activity. Both mechanisms together account for almost of C. albicans killing, clearly proving that beside being present in larger numbers than other leukocytes, neutrophils functionally dominate the immune response against C. albicans in human blood. A fraction of C. albicans cells escaped phagocytosis and remained extracellular and viable for up to four hours. This immune escape was independent of filamentation and fungal activity and not linked to exhaustion or inactivation of innate immune cells. The occurrence of C. albicans cells being resistant against phagocytosis may account for the high proportion of dissemination in C. albicans bloodstream infection. Taken together, iterative experiment–model–experiment cycles allowed quantitative analyses of the interplay between host and pathogen in a complex environment like human blood. PMID:24586131

A virtual infection model quantifies innate effector mechanisms and Candida albicans immune escape in human blood.

PubMed

Hünniger, Kerstin; Lehnert, Teresa; Bieber, Kristin; Martin, Ronny; Figge, Marc Thilo; Kurzai, Oliver

2014-02-01

Candida albicans bloodstream infection is increasingly frequent and can result in disseminated candidiasis associated with high mortality rates. To analyze the innate immune response against C. albicans, fungal cells were added to human whole-blood samples. After inoculation, C. albicans started to filament and predominantly associate with neutrophils, whereas only a minority of fungal cells became attached to monocytes. While many parameters of host-pathogen interaction were accessible to direct experimental quantification in the whole-blood infection assay, others were not. To overcome these limitations, we generated a virtual infection model that allowed detailed and quantitative predictions on the dynamics of host-pathogen interaction. Experimental time-resolved data were simulated using a state-based modeling approach combined with the Monte Carlo method of simulated annealing to obtain quantitative predictions on a priori unknown transition rates and to identify the main axis of antifungal immunity. Results clearly demonstrated a predominant role of neutrophils, mediated by phagocytosis and intracellular killing as well as the release of antifungal effector molecules upon activation, resulting in extracellular fungicidal activity. Both mechanisms together account for almost [Formula: see text] of C. albicans killing, clearly proving that beside being present in larger numbers than other leukocytes, neutrophils functionally dominate the immune response against C. albicans in human blood. A fraction of C. albicans cells escaped phagocytosis and remained extracellular and viable for up to four hours. This immune escape was independent of filamentation and fungal activity and not linked to exhaustion or inactivation of innate immune cells. The occurrence of C. albicans cells being resistant against phagocytosis may account for the high proportion of dissemination in C. albicans bloodstream infection. Taken together, iterative experiment-model-experiment cycles allowed quantitative analyses of the interplay between host and pathogen in a complex environment like human blood.

Uncovering plant-pathogen crosstalk through apoplastic proteomic studies.

PubMed

Delaunois, Bertrand; Jeandet, Philippe; Clément, Christophe; Baillieul, Fabienne; Dorey, Stéphan; Cordelier, Sylvain

2014-01-01

Plant pathogens have evolved by developing different strategies to infect their host, which in turn have elaborated immune responses to counter the pathogen invasion. The apoplast, including the cell wall and extracellular space outside the plasma membrane, is one of the first compartments where pathogen-host interaction occurs. The plant cell wall is composed of a complex network of polysaccharides polymers and glycoproteins and serves as a natural physical barrier against pathogen invasion. The apoplastic fluid, circulating through the cell wall and intercellular spaces, provides a means for delivering molecules and facilitating intercellular communications. Some plant-pathogen interactions lead to plant cell wall degradation allowing pathogens to penetrate into the cells. In turn, the plant immune system recognizes microbial- or damage-associated molecular patterns (MAMPs or DAMPs) and initiates a set of basal immune responses, including the strengthening of the plant cell wall. The establishment of defense requires the regulation of a wide variety of proteins that are involved at different levels, from receptor perception of the pathogen via signaling mechanisms to the strengthening of the cell wall or degradation of the pathogen itself. A fine regulation of apoplastic proteins is therefore essential for rapid and effective pathogen perception and for maintaining cell wall integrity. This review aims to provide insight into analyses using proteomic approaches of the apoplast to highlight the modulation of the apoplastic protein patterns during pathogen infection and to unravel the key players involved in plant-pathogen interaction.

Understanding immunology: fun at an intersection of the physical, life, and clinical sciences

NASA Astrophysics Data System (ADS)

Chakraborty, Arup K.

2014-10-01

Understanding how the immune system works is a grand challenge in science with myriad direct implications for improving human health. The immune system protects us from infectious pathogens and cancer, and maintains a harmonious steady state with essential microbiota in our gut. Vaccination, the medical procedure that has saved more lives than any other, involves manipulating the immune system. Unfortunately, the immune system can also go awry to cause autoimmune diseases. Immune responses are the product of stochastic collective dynamic processes involving many interacting components. These processes span multiple scales of length and time. Thus, statistical mechanics has much to contribute to immunology, and the oeuvre of biological physics will be further enriched if the number of physical scientists interested in immunology continues to increase. I describe how I got interested in immunology and provide a glimpse of my experiences working on immunology using approaches from statistical mechanics and collaborating closely with immunologists.

Infection-Induced Interaction between the Mosquito Circulatory and Immune Systems

PubMed Central

King, Jonas G.; Hillyer, Julián F.

2012-01-01

Insects counter infection with innate immune responses that rely on cells called hemocytes. Hemocytes exist in association with the insect's open circulatory system and this mode of existence has likely influenced the organization and control of anti-pathogen immune responses. Previous studies reported that pathogens in the mosquito body cavity (hemocoel) accumulate on the surface of the heart. Using novel cell staining, microdissection and intravital imaging techniques, we investigated the mechanism of pathogen accumulation in the pericardium of the malaria mosquito, Anopheles gambiae, and discovered a novel insect immune tissue, herein named periostial hemocytes, that sequesters pathogens as they flow with the hemolymph. Specifically, we show that there are two types of endocytic cells that flank the heart: periostial hemocytes and pericardial cells. Resident periostial hemocytes engage in the rapid phagocytosis of pathogens, and during the course of a bacterial or Plasmodium infection, circulating hemocytes migrate to the periostial regions where they bind the cardiac musculature and each other, and continue the phagocytosis of invaders. Periostial hemocyte aggregation occurs in a time- and infection dose-dependent manner, and once this immune process is triggered, the number of periostial hemocytes remains elevated for the lifetime of the mosquito. Finally, the soluble immune elicitors peptidoglycan and β-1,3-glucan also induce periostial hemocyte aggregation, indicating that this is a generalized and basal immune response that is induced by diverse immune stimuli. These data describe a novel insect cellular immune response that fundamentally relies on the physiological interaction between the insect circulatory and immune systems. PMID:23209421

Plant innate immunity: an updated insight into defense mechanism.

PubMed

Muthamilarasan, Mehanathan; Prasad, Manoj

2013-06-01

Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and effector-triggered immunity (ETI). MTI confers basal resistance, while ETI confers durable resistance, often resulting in hypersensitive response. Plants also possess systemic acquired resistance (SAR), which provides long-term defense against a broad-spectrum of pathogens. Salicylic-acid-mediated systemic acquired immunity provokes the defense response throughout the plant system during pathogen infection at a particular site. Trans-generational immune priming allows the plant to heritably shield their progeny towards pathogens previously encountered. Plants circumvent the viral infection through RNA interference phenomena by utilizing small RNAs. This review summarizes the molecular mechanisms of plant immune system, and the latest breakthroughs reported in plant defense. We discuss the plant–pathogen interactions and integrated defense responses in the context of presenting an integral understanding in plant molecular immunity.

Vitamin D Status and the Host Resistance to Infections: What It Is Currently (Not) Understood.

PubMed

Lang, Pierre Olivier; Aspinall, Richard

2017-05-01

Vitamin D is increasingly thought to play a role in regulating immunity. This comprehensive review updates the current understanding regarding ways in which we believe that vitamin D regulates responsiveness of the immune system and how serum status modulates the host defense against pathogens. The literature was searched by using PubMed and Scopus with the following key words: vitamin D, immunity, innate and adaptive immunity, infectious disease, and vaccine response. Vitamin D deficiency remains a major public health concern worldwide. The overall body of evidence confirms that vitamin D plays an important role in modulating the immune response to infections. Epidemiologic studies suggest a clear association between vitamin D deficiency and susceptibility to various pathogens. However, translation of vitamin D use into the clinic as a means of controlling infections is fraught with methodologic and epidemiologic challenges. The recent discovery of alternative activation pathways, different active forms of vitamin D, and possible interaction with non-vitamin D receptors provide further complications to an already complex interaction between vitamin D and the immune system. Moreover, it has become apparent that the individual responsiveness to supplementation is more dynamic than presumed from the static assessment of 25-hydroxy vitamin D status. Furthermore, the epigenetic response at the level of the individual to environmental changes and lifestyle or health conditions provides greater variation than those resulting from vitamin D receptor polymorphisms. To understand the future of vitamin D with respect to clinical applications in the prevention and better control of infectious diseases, it is necessary to determine all aspects of vitamin D metabolism, as well as the mechanisms by which active forms interact with the immune system globally. For the most part, we are unable to identify tissue-specific applications of supplementation except for those subjects at high risk of osteomalacia and osteoporosis. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

The Plant Actin Cytoskeleton Responds to Signals from Microbe-Associated Molecular Patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henty-Ridilla, Jessica L.; Shimono, Masaki; Li, Jiejie

2013-04-04

Plants are constantly exposed to a large and diverse array of microbes; however, most plants are immune to the majority of potential invaders and susceptible to only a small subset of pathogens. The cytoskeleton comprises a dynamic intracellular framework that responds rapidly to biotic stresses and supports numerous fundamental cellular processes including vesicle trafficking, endocytosis and the spatial distribution of organelles and protein complexes. For years, the actin cytoskeleton has been assumed to play a role in plant innate immunity against fungi and oomycetes, based largely on static images and pharmacological studies. To date, however, there is little evidence thatmore » the host-cell actin cytoskeleton participates in responses to phytopathogenic bacteria. Here, we quantified the spatiotemporal changes in host-cell cytoskeletal architecture during the immune response to pathogenic and non-pathogenic strains of Pseudomonas syringae pv. tomato DC3000. Two distinct changes to host cytoskeletal arrays were observed that correspond to distinct phases of plant-bacterial interactions i.e. the perception of microbe-associated molecular patterns (MAMPs) during pattern-triggered immunity (PTI) and perturbations by effector proteins during effector-triggered susceptibility (ETS). We demonstrate that an immediate increase in actin filament abundance is a conserved and novel component of PTI. Notably, treatment of leaves with a MAMP peptide mimic was sufficient to elicit a rapid change in actin organization in epidermal cells, and this actin response required the host-cell MAMP receptor kinase complex, including FLS2, BAK1 and BIK1. Finally, we found that actin polymerization is necessary for the increase in actin filament density and that blocking this increase with the actin-disrupting drug latrunculin B leads to enhanced susceptibility of host plants to pathogenic and non-pathogenic bacteria.« less

The Complex Contributions of Genetics and Nutrition to Immunity in Drosophila melanogaster

PubMed Central

Unckless, Robert L.; Rottschaefer, Susan M.; Lazzaro, Brian P.

2015-01-01

Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and “nutritional immunology” has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional “immune system” that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment. PMID:25764027

The complex contributions of genetics and nutrition to immunity in Drosophila melanogaster.

PubMed

Unckless, Robert L; Rottschaefer, Susan M; Lazzaro, Brian P

2015-03-01

Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and "nutritional immunology" has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional "immune system" that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment.

The effect of seasonal birth pulses on pathogen persistence in wild mammal populations.

PubMed

Peel, A J; Pulliam, J R C; Luis, A D; Plowright, R K; O'Shea, T J; Hayman, D T S; Wood, J L N; Webb, C T; Restif, O

2014-07-07

The notion of a critical community size (CCS), or population size that is likely to result in long-term persistence of a communicable disease, has been developed based on the empirical observations of acute immunizing infections in human populations, and extended for use in wildlife populations. Seasonal birth pulses are frequently observed in wildlife and are expected to impact infection dynamics, yet their effect on pathogen persistence and CCS have not been considered. To investigate this issue theoretically, we use stochastic epidemiological models to ask how host life-history traits and infection parameters interact to determine pathogen persistence within a closed population. We fit seasonal birth pulse models to data from diverse mammalian species in order to identify realistic parameter ranges. When varying the synchrony of the birth pulse with all other parameters being constant, our model predicted that the CCS can vary by more than two orders of magnitude. Tighter birth pulses tended to drive pathogen extinction by creating large amplitude oscillations in prevalence, especially with high demographic turnover and short infectious periods. Parameters affecting the relative timing of the epidemic and birth pulse peaks determined the intensity and direction of the effect of pre-existing immunity in the population on the pathogen's ability to persist beyond the initial epidemic following its introduction.

The effect of seasonal birth pulses on pathogen persistence in wild mammal populations

PubMed Central

Peel, A. J.; Pulliam, J. R. C.; Luis, A. D.; Plowright, R. K.; O'Shea, T. J.; Hayman, D. T. S.; Wood, J. L. N.; Webb, C. T.; Restif, O.

2014-01-01

The notion of a critical community size (CCS), or population size that is likely to result in long-term persistence of a communicable disease, has been developed based on the empirical observations of acute immunizing infections in human populations, and extended for use in wildlife populations. Seasonal birth pulses are frequently observed in wildlife and are expected to impact infection dynamics, yet their effect on pathogen persistence and CCS have not been considered. To investigate this issue theoretically, we use stochastic epidemiological models to ask how host life-history traits and infection parameters interact to determine pathogen persistence within a closed population. We fit seasonal birth pulse models to data from diverse mammalian species in order to identify realistic parameter ranges. When varying the synchrony of the birth pulse with all other parameters being constant, our model predicted that the CCS can vary by more than two orders of magnitude. Tighter birth pulses tended to drive pathogen extinction by creating large amplitude oscillations in prevalence, especially with high demographic turnover and short infectious periods. Parameters affecting the relative timing of the epidemic and birth pulse peaks determined the intensity and direction of the effect of pre-existing immunity in the population on the pathogen's ability to persist beyond the initial epidemic following its introduction. PMID:24827436

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis.

PubMed

Rizzuto, Gabrielle; Tagliani, Elisa; Manandhar, Priyanka; Erlebacher, Adrian; Bakardjiev, Anna I

2017-08-01

The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of L. monocytogenes infection in primary human decidual organ cultures and in the murine decidua in vivo A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses against L. monocytogenes in the spleen, as well as a decrease in the tissue density of inflammatory Ly6C hi monocytes in vivo These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment of L. monocytogenes to the gestational uterus but rather is due to compromised local innate cellular immune responses. Copyright © 2017 American Society for Microbiology.

Interaction of pathogens with host cholesterol metabolism.

PubMed

Sviridov, Dmitri; Bukrinsky, Michael

2014-10-01

Pathogens of different taxa, from prions to protozoa, target cellular cholesterol metabolism to advance their own development and to impair host immune responses, but also causing metabolic complications, for example, atherosclerosis. This review describes recent findings of how pathogens do it. A common theme in interaction between pathogens and host cholesterol metabolism is pathogens targeting lipid rafts of the host plasma membrane. Many intracellular pathogens use rafts as an entry gate, taking advantage of the endocytic machinery and high abundance of outward-looking molecules that can be used as receptors. At the same time, disruption of the rafts' functional capacity, achieved by the pathogens through a number of various means, impairs the ability of the host to generate immune response, thus helping pathogen to thrive. Pathogens cannot synthesize cholesterol, and salvaging host cholesterol helps pathogens build advanced cholesterol-containing membranes and assembly platforms. Impact on cholesterol metabolism is not limited to the infected cells; proteins and microRNAs secreted by infected cells affect lipid metabolism systemically. Given an essential role that host cholesterol metabolism plays in pathogen development, targeting this interaction may be a viable strategy to fight infections, as well as metabolic complications of the infections.

T cell-B cell interactions in primary immunodeficiencies.

PubMed

Tangye, Stuart G; Deenick, Elissa K; Palendira, Umaimainthan; Ma, Cindy S

2012-02-01

Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4(+) T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8(+) T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. © 2012 New York Academy of Sciences.

Mechanisms of innate immune evasion in re-emerging RNA viruses.

PubMed

Ma, Daphne Y; Suthar, Mehul S

2015-06-01

Recent outbreaks of Ebola, West Nile, Chikungunya, Middle Eastern Respiratory and other emerging/re-emerging RNA viruses continue to highlight the need to further understand the virus-host interactions that govern disease severity and infection outcome. As part of the early host antiviral defense, the innate immune system mediates pathogen recognition and initiation of potent antiviral programs that serve to limit virus replication, limit virus spread and activate adaptive immune responses. Concordantly, viral pathogens have evolved several strategies to counteract pathogen recognition and cell-intrinsic antiviral responses. In this review, we highlight the major mechanisms of innate immune evasion by emerging and re-emerging RNA viruses, focusing on pathogens that pose significant risk to public health. Copyright © 2015 Elsevier B.V. All rights reserved.

Molecular Determinants in Phagocyte-Bacteria Interactions.

PubMed

Kaufmann, Stefan H E; Dorhoi, Anca

2016-03-15

Phagocytes are crucial for host defense against bacterial pathogens. As first demonstrated by Metchnikoff, neutrophils and mononuclear phagocytes share the capacity to engulf, kill, and digest microbial invaders. Generally, neutrophils focus on extracellular, and mononuclear phagocytes on intracellular, pathogens. Reciprocally, extracellular pathogens often capitalize on hindering phagocytosis and killing of phagocytes, whereas intracellular bacteria frequently allow their engulfment and then block intracellular killing. As foreseen by Metchnikoff, phagocytes become highly versatile by acquiring diverse phenotypes, but still retaining some plasticity. Further, phagocytes engage in active crosstalk with parenchymal and immune cells to promote adjunctive reactions, including inflammation, tissue healing, and remodeling. This dynamic network allows the host to cope with different types of microbial invaders. Here we present an update of molecular and cellular mechanisms underlying phagocyte functions in antibacterial defense. We focus on four exemplary bacteria ranging from an opportunistic extracellular to a persistent intracellular pathogen. Copyright © 2016 Elsevier Inc. All rights reserved.

Robustness trade-offs and host–microbial symbiosis in the immune system

PubMed Central

Kitano, Hiroaki; Oda, Kanae

2006-01-01

The immune system provides organisms with robustness against pathogen threats, yet it also often adversely affects the organism as in autoimmune diseases. Recently, the molecular interactions involved in the immune system have been uncovered. At the same time, the role of the bacterial flora and its interactions with the host immune system have been identified. In this article, we try to reconcile these findings to draw a consistent picture of the host defense system. Specifically, we first argue that the network of molecular interactions involved in immune functions has a bow-tie architecture that entails inherent trade-offs among robustness, fragility, resource limitation, and performance. Second, we discuss the possibility that commensal bacteria and the host immune system constitute an integrated defense system. This symbiotic association has evolved to optimize its robustness against pathogen attacks and nutrient perturbations by harboring a broad range of microorganisms. Owing to the inherent propensity of a host immune system toward hyperactivity, maintenance of bacterial flora homeostasis might be particularly important in the development of preventive strategies against immune disorders such as autoimmune diseases. PMID:16738567

The effect of pre-laying maternal immunization on offspring growth and immunity differs across experimentally altered postnatal rearing conditions in a wild songbird.

PubMed

Martyka, Rafał; Śliwińska, Ewa B; Martyka, Mirosław; Cichoń, Mariusz; Tryjanowski, Piotr

2018-01-01

Prenatal antibody transfer is an immune-mediated maternal effect by which females can shape postnatal offspring resistance to pathogens and parasites. Maternal antibodies passed on to offspring provide primary protection to neonates against diverse pathogenic antigens, but they may also affect offspring growth and influence the development of an offspring's own immune response. The effects of maternal antibodies on offspring performance commonly require that the disease environment experienced by a mother prior to breeding matches the environment encountered by her offspring after hatching/birth. However, other circumstances, like postnatal rearing conditions that affect offspring food availability, may also determine the effects of maternal antibodies on offspring growth and immunity. To date, knowledge about how prenatal immune-mediated maternal effects interact with various postnatal rearing conditions to affect offspring development and phenotype in wild bird population remains elusive. Here we experimentally studied the interactive effects of pre-laying maternal immunization with a bacterial antigen (lipopolysaccharide) and post-hatching rearing conditions, altered by brood size manipulation, on offspring growth and humoral immunity of wild great tits ( Parus major ). We found that maternal immunization and brood size manipulation interactively affected the growth and specific humoral immune response of avian offspring. Among nestlings reared in enlarged broods, only those that originated from immunized mothers grew better and were heavier at fledging stage compared to those that originated from non-immunized mothers. In contrast, no such effects were observed among nestlings reared in non-manipulated (control) broods. Moreover, offspring of immunized females had a stronger humoral immune response to lipopolysaccharide during postnatal development than offspring of non-immunized females, but only when the nestling was reared in control broods. This study demonstrates that offspring development and their ability to cope with pathogens after hatching are driven by mutual influences of pathogen-induced prenatal maternal effects and post-hatching rearing conditions. Our findings suggest that immune-mediated maternal effects may have context-dependent influences on offspring growth and immune function, related to the postnatal environmental conditions experienced by the progeny.

Sea fan immunity and disease is influenced by metal pollution, host demography, and multiple stressors

NASA Astrophysics Data System (ADS)

Tracy, A. M.; Weil, E.; Harvell, C. D.

2016-02-01

Organisms in natural populations experience an onslaught of stressful conditions that may compromise their ability to fight pathogens, particularly if multiple stressors impact a host at the same time. Environmental stressors can also influence the pathogens. Despite the clear importance of environmental factors for coral host-pathogen interactions and the potential for population-level consequences, there is relatively little research to date on multiple stressors. The population of Caribbean sea fans, Gorgonia ventalina, in Parguera, Puerto Rico is a tractable system in which to study the effects of multiple stressors on two pathogens. Sea fans are dominant members of reefs that provide food and habitat for diverse reef inhabitants. In addition, there is already a foundation of research on sea fan disease and immunity. We first conducted field surveys of 15 sites to assess the effects of demographic and environmental factors on the prevalence and severity of multifocal purple spots (MFPS) and a Labyrinthulid stramenopile pathogen, as well as the host's cellular immune response to each pathogen. We complemented the field survey with a fully factorial, clonally replicated experiment on the separate and combined effects of thermal stress and copper pollution on both the host and the pathogen. Although water quality has been linked to coral disease, there are no studies investigating the role of metal or chemical pollutants, which are high at some of our study sites. Preliminary results show that the sea fan immune response to the Labyrinthulid depends on interactive effects of copper and thermal stress. The field survey identifies colony size as the main driver of MFPS. This in-depth perspective on sea fan disease speaks to the immune capabilities of cnidarians, highlights factors that modify those capabilities, and reflects the complex interaction of host, pathogens, and environment in this ecologically important coral.

A bacterial siren song: intimate interactions between neutrophils and pathogenic Neisseria

PubMed Central

Criss, Alison K.; Seifert, H. Steven

2012-01-01

Preface Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that are exquisitely adapted for growth at human mucosal surfaces and for efficient transmission between hosts. One factor that is essential to neisserial pathogenesis is the interaction between the bacteria and neutrophils, which are recruited in high numbers during infection. Although this vigorous host response could simply reflect effective immune recognition of the bacteria, there is mounting evidence that in fact these obligate human pathogens manipulate the innate immune response to promote infectious processes. This Review summarizes the mechanisms used by pathogenic neisseriae to resist and modulate the antimicrobial activities of neutrophils. It also details some of the major outstanding questions about the Neisseria–neutrophil relationship and proposes potential benefits of this relationship for the pathogen. PMID:22290508

Effects of co-occurring Wolbachia and Spiroplasma endosymbionts on the Drosophila immune response against insect pathogenic and non-pathogenic bacteria.

PubMed

Shokal, Upasana; Yadav, Shruti; Atri, Jaishri; Accetta, Julia; Kenney, Eric; Banks, Katherine; Katakam, Akash; Jaenike, John; Eleftherianos, Ioannis

2016-02-09

Symbiotic interactions between microbes and animals are common in nature. Symbiotic organisms are particularly common in insects and, in some cases, they may protect their hosts from pathogenic infections. Wolbachia and Spiroplasma endosymbionts naturally inhabit various insects including Drosophila melanogaster fruit flies. Therefore, this symbiotic association is considered an excellent model to investigate whether endosymbiotic bacteria participate in host immune processes against certain pathogens. Here we have investigated whether the presence of Wolbachia alone or together with Spiroplasma endosymbionts in D. melanogaster adult flies affects the immune response against the virulent insect pathogen Photorhabdus luminescens and against non-pathogenic Escherichia coli bacteria. We found that D. melanogaster flies carrying no endosymbionts, those carrying both Wolbachia and Spiroplasma, and those containing Wolbachia only had similar survival rates after infection with P. luminescens or Escherichia coli bacteria. However, flies carrying both endosymbionts or Wolbachia only contained higher numbers of E. coli cells at early time-points post infection than flies without endosymbiotic bacteria. Interestingly, flies containing Wolbachia only had lower titers of this endosymbiont upon infection with the pathogen P. luminescens than uninfected flies of the same strain. We further found that the presence of Wolbachia and Spiroplasma in D. melanogaster up-regulated certain immune-related genes upon infection with P. luminescens or E. coli bacteria, but it failed to alter the phagocytic ability of the flies toward E. coli inactive bioparticles. Our results suggest that the presence of Wolbachia and Spiroplasma in D. melanogaster can modulate immune signaling against infection by certain insect pathogenic and non-pathogenic bacteria. Results from such studies are important for understanding the molecular basis of the interactions between endosymbiotic bacteria of insects and exogenous microbes.

Candidate innate immune system gene expression in the ecological model Daphnia

PubMed Central

Decaestecker, Ellen; Labbé, Pierrick; Ellegaard, Kirsten; Allen, Judith E.; Little, Tom J.

2011-01-01

The last ten years have witnessed increasing interest in host–pathogen interactions involving invertebrate hosts. The invertebrate innate immune system is now relatively well characterised, but in a limited range of genetic model organisms and under a limited number of conditions. Immune systems have been little studied under real-world scenarios of environmental variation and parasitism. Thus, we have investigated expression of candidate innate immune system genes in the water flea Daphnia, a model organism for ecological genetics, and whose capacity for clonal reproduction facilitates an exceptionally rigorous control of exposure dose or the study of responses at many time points. A unique characteristic of the particular Daphnia clones and pathogen strain combinations used presently is that they have been shown to be involved in specific host–pathogen coevolutionary interactions in the wild. We choose five genes, which are strong candidates to be involved in Daphnia–pathogen interactions, given that they have been shown to code for immune effectors in related organisms. Differential expression of these genes was quantified by qRT-PCR following exposure to the bacterial pathogen Pasteuria ramosa. Constitutive expression levels differed between host genotypes, and some genes appeared to show correlated expression. However, none of the genes appeared to show a major modification of expression level in response to Pasteuria exposure. By applying knowledge from related genetic model organisms (e.g. Drosophila) to models for the study of evolutionary ecology and coevolution (i.e. Daphnia), the candidate gene approach is temptingly efficient. However, our results show that detection of only weak patterns is likely if one chooses target genes for study based on previously identified genome sequences by comparison to homologues from other related organisms. Future work on the Daphnia–Pasteuria system will need to balance a candidate gene approach with more comprehensive approaches to de novo identify immune system genes specific to the Daphnia–Pasteuria interaction. PMID:21550363

Candidate innate immune system gene expression in the ecological model Daphnia.

PubMed

Decaestecker, Ellen; Labbé, Pierrick; Ellegaard, Kirsten; Allen, Judith E; Little, Tom J

2011-10-01

The last ten years have witnessed increasing interest in host-pathogen interactions involving invertebrate hosts. The invertebrate innate immune system is now relatively well characterised, but in a limited range of genetic model organisms and under a limited number of conditions. Immune systems have been little studied under real-world scenarios of environmental variation and parasitism. Thus, we have investigated expression of candidate innate immune system genes in the water flea Daphnia, a model organism for ecological genetics, and whose capacity for clonal reproduction facilitates an exceptionally rigorous control of exposure dose or the study of responses at many time points. A unique characteristic of the particular Daphnia clones and pathogen strain combinations used presently is that they have been shown to be involved in specific host-pathogen coevolutionary interactions in the wild. We choose five genes, which are strong candidates to be involved in Daphnia-pathogen interactions, given that they have been shown to code for immune effectors in related organisms. Differential expression of these genes was quantified by qRT-PCR following exposure to the bacterial pathogen Pasteuria ramosa. Constitutive expression levels differed between host genotypes, and some genes appeared to show correlated expression. However, none of the genes appeared to show a major modification of expression level in response to Pasteuria exposure. By applying knowledge from related genetic model organisms (e.g. Drosophila) to models for the study of evolutionary ecology and coevolution (i.e. Daphnia), the candidate gene approach is temptingly efficient. However, our results show that detection of only weak patterns is likely if one chooses target genes for study based on previously identified genome sequences by comparison to homologues from other related organisms. Future work on the Daphnia-Pasteuria system will need to balance a candidate gene approach with more comprehensive approaches to de novo identify immune system genes specific to the Daphnia-Pasteuria interaction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bacterial effector HopF2 interacts with AvrPto and suppresses Arabidopsis innate immunity at the plasma membrane

USDA-ARS?s Scientific Manuscript database

Plant pathogenic bacteria inject a cocktail of effector proteins into host plant cells to modulate the host immune response, thereby promoting pathogenicity. How or whether these effectors work cooperatively is largely unknown. The Pseudomonas syringae DC3000 effector HopF2 suppresses the host plan...

Skin Immune Landscape: Inside and Outside the Organism.

PubMed

Abdallah, Florence; Mijouin, Lily; Pichon, Chantal

2017-01-01

The skin is an essential organ to the human body protecting it from external aggressions and pathogens. Over the years, the skin was proven to have a crucial immunological role, not only being a passive protective barrier but a network of effector cells and molecular mediators that constitute a highly sophisticated compound known as the "skin immune system" (SIS). Studies of skin immune sentinels provided essential insights of a complex and dynamic immunity, which was achieved through interaction between the external and internal cutaneous compartments. In fact, the skin surface is cohabited by microorganisms recognized as skin microbiota that live in complete harmony with the immune sentinels and contribute to the epithelial barrier reinforcement. However, under stress, the symbiotic relationship changes into a dysbiotic one resulting in skin disorders. Hence, the skin microbiota may have either positive or negative influence on the immune system. This review aims at providing basic background information on the cutaneous immune system from major cellular and molecular players and the impact of its microbiota on the well-coordinated immune responses in host defense.

Plant immunity: a lesson from pathogenic bacterial effector proteins.

PubMed

Cui, Haitao; Xiang, Tingting; Zhou, Jian-Min

2009-10-01

Phytopathogenic bacteria inject an array of effector proteins into host cells to alter host physiology and assist the infection process. Some of these effectors can also trigger disease resistance as a result of recognition in the plant cell by cytoplasmic immune receptors. In addition to effector-triggered immunity, plants immunity can be triggered upon the detection of Pathogen/Microbe-Associated Molecular Patterns by surface-localized immune receptors. Recent progress indicates that many bacterial effector proteins use a variety of biochemical properties to directly attack key components of PAMP-triggered immunity and effector-triggered immunity, providing new insights into the molecular basis of plant innate immunity. Emerging evidence indicate that the evolution of disease resistance in plants is intimately linked to the mechanism by which bacterial effectors promote parasitism. This review focuses on how these studies have conceptually advanced our understanding of plant-pathogen interactions.

Spiroplasma and host immunity: activation of humoral immune responses increases endosymbiont load and susceptibility to certain Gram-negative bacterial pathogens in Drosophila melanogaster.

PubMed

Herren, Jeremy K; Lemaitre, Bruno

2011-09-01

Spiroplasma poulsonii and its relatives are facultative, vertically transmitted endosymbionts harboured by several Drosophila species. Their long-term survival requires not only evasion of host immunity, but also that Spiroplasma does not have a net detrimental effect on host fitness. These requirements provide the central framework for interactions between host and endosymbiont. We use Drosophila melaogaster as a model to unravel aspects of the mechanistic basis of endosymbiont-host immune interactions. Here we show that Spiroplasma does not activate an immune response in Drosophila and is not susceptible to either the cellular or humoral arms of the Drosophila immune system. We gain unexpected insight into host factors that can promote Spiroplasma growth by showing that activation of Toll and Imd immune pathways actually increases Sprioplasma titre. Spiroplasma-mediated protection is not observed for variety of fungal and bacterial pathogens and Spiroplasma actually increases susceptibility of Drosophila to certain Gram-negative pathogens. Finally, we show that the growth of endosymbiotic Spiroplasma is apparently self-regulated, as suggested by the unhindered proliferation of non-endosymbiotic Spiroplasma citri in fly haemolymph. © 2011 Blackwell Publishing Ltd.

Modeling the interactions between pathogenic bacteria, bacteriophage and immune response

NASA Astrophysics Data System (ADS)

Leung, Chung Yin (Joey); Weitz, Joshua S.

The prevalence of antibiotic-resistant strains of pathogenic bacteria has led to renewed interest in the use of bacteriophage (phage), or virus that infects bacteria, as a therapeutic agent against bacterial infections. However, little is known about the theoretical mechanism by which phage therapy may work. In particular, interactions between the bacteria, the phage and the host immune response crucially influences the outcome of the therapy. Few models of phage therapy have incorporated all these three components, and existing models suffer from unrealistic assumptions such as unbounded growth of the immune response. We propose a model of phage therapy with an emphasis on nonlinear feedback arising from interactions with bacteria and the immune response. Our model shows a synergistic effect between the phage and the immune response which underlies a possible mechanism for phage to catalyze the elimination of bacteria even when neither the immune response nor phage could do so alone. We study the significance of this effect for different parameters of infection and immune response, and discuss its implications for phage therapy.

Immune Receptors and Co-receptors in Antiviral Innate Immunity in Plants.

PubMed

Gouveia, Bianca C; Calil, Iara P; Machado, João Paulo B; Santos, Anésia A; Fontes, Elizabeth P B

2016-01-01

Plants respond to pathogens using an innate immune system that is broadly divided into PTI (pathogen-associated molecular pattern- or PAMP-triggered immunity) and ETI (effector-triggered immunity). PTI is activated upon perception of PAMPs, conserved motifs derived from pathogens, by surface membrane-anchored pattern recognition receptors (PRRs). To overcome this first line of defense, pathogens release into plant cells effectors that inhibit PTI and activate effector-triggered susceptibility (ETS). Counteracting this virulence strategy, plant cells synthesize intracellular resistance (R) proteins, which specifically recognize pathogen effectors or avirulence (Avr) factors and activate ETI. These coevolving pathogen virulence strategies and plant resistance mechanisms illustrate evolutionary arms race between pathogen and host, which is integrated into the zigzag model of plant innate immunity. Although antiviral immune concepts have been initially excluded from the zigzag model, recent studies have provided several lines of evidence substantiating the notion that plants deploy the innate immune system to fight viruses in a manner similar to that used for non-viral pathogens. First, most R proteins against viruses so far characterized share structural similarity with antibacterial and antifungal R gene products and elicit typical ETI-based immune responses. Second, virus-derived PAMPs may activate PTI-like responses through immune co-receptors of plant PTI. Finally, and even more compelling, a viral Avr factor that triggers ETI in resistant genotypes has recently been shown to act as a suppressor of PTI, integrating plant viruses into the co-evolutionary model of host-pathogen interactions, the zigzag model. In this review, we summarize these important progresses, focusing on the potential significance of antiviral immune receptors and co-receptors in plant antiviral innate immunity. In light of the innate immune system, we also discuss a newly uncovered layer of antiviral defense that is specific to plant DNA viruses and relies on transmembrane receptor-mediated translational suppression for defense.

Effector-triggered immunity: from pathogen perception to robust defense.

PubMed

Cui, Haitao; Tsuda, Kenichi; Parker, Jane E

2015-01-01

In plant innate immunity, individual cells have the capacity to sense and respond to pathogen attack. Intracellular recognition mechanisms have evolved to intercept perturbations by pathogen virulence factors (effectors) early in host infection and convert it to rapid defense. One key to resistance success is a polymorphic family of intracellular nucleotide-binding/leucine-rich-repeat (NLR) receptors that detect effector interference in different parts of the cell. Effector-activated NLRs connect, in various ways, to a conserved basal resistance network in order to transcriptionally boost defense programs. Effector-triggered immunity displays remarkable robustness against pathogen disturbance, in part by employing compensatory mechanisms within the defense network. Also, the mobility of some NLRs and coordination of resistance pathways across cell compartments provides flexibility to fine-tune immune outputs. Furthermore, a number of NLRs function close to the nuclear chromatin by balancing actions of defense-repressing and defense-activating transcription factors to program cells dynamically for effective disease resistance.

GSL-enriched membrane microdomains in innate immune responses.

PubMed

Nakayama, Hitoshi; Ogawa, Hideoki; Takamori, Kenji; Iwabuchi, Kazuhisa

2013-06-01

Many pathogens target glycosphingolipids (GSLs), which, together with cholesterol, GPI-anchored proteins, and various signaling molecules, cluster on host cell membranes to form GSL-enriched membrane microdomains (lipid rafts). These GSL-enriched membrane microdomains may therefore be involved in host-pathogen interactions. Innate immune responses are triggered by the association of pathogens with phagocytes, such as neutrophils, macrophages and dendritic cells. Phagocytes express a diverse array of pattern-recognition receptors (PRRs), which sense invading microorganisms and trigger pathogen-specific signaling. PRRs can recognize highly conserved pathogen-associated molecular patterns expressed on microorganisms. The GSL lactosylceramide (LacCer, CDw17), which binds to various microorganisms, including Candida albicans, is expressed predominantly on the plasma membranes of human mature neutrophils and forms membrane microdomains together with the Src family tyrosine kinase Lyn. These LacCer-enriched membrane microdomains can mediate superoxide generation, migration, and phagocytosis, indicating that LacCer functions as a PRR in innate immunity. Moreover, the interactions of GSL-enriched membrane microdomains with membrane proteins, such as growth factor receptors, are important in mediating the physiological properties of these proteins. Similarly, we recently found that interactions between LacCer-enriched membrane microdomains and CD11b/CD18 (Mac-1, CR3, or αMβ2-integrin) are significant for neutrophil phagocytosis of non-opsonized microorganisms. This review describes the functional role of LacCer-enriched membrane microdomains and their interactions with CD11b/CD18.

Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi.

PubMed

Mylonakis, Eleftherios; Casadevall, Arturo; Ausubel, Frederick M

2007-07-27

Experiments with insects, protozoa, nematodes, and slime molds have recently come to the forefront in the study of host-fungal interactions. Many of the virulence factors required for pathogenicity in mammals are also important for fungal survival during interactions with non-vertebrate hosts, suggesting that fungal virulence may have evolved, and been maintained, as a countermeasure to environmental predation by amoebae and nematodes and other small non-vertebrates that feed on microorganisms. Host innate immune responses are also broadly conserved across many phyla. The study of the interaction between invertebrate model hosts and pathogenic fungi therefore provides insights into the mechanisms underlying pathogen virulence and host immunity, and complements the use of mammalian models by enabling whole-animal high throughput infection assays. This review aims to assist researchers in identifying appropriate invertebrate systems for the study of particular aspects of fungal pathogenesis.

Intersections between immune responses and morphological regulation in plants.

PubMed

Uchida, Naoyuki; Tasaka, Masao

2010-06-01

Successful plant pathogens have developed strategies to interfere with the defence mechanisms of their host plants through evolution. Conversely, host plants have evolved systems to counteract pathogen attack. Some pathogens induce pathogenic symptoms on plants that include morphological changes in addition to interference with plant growth. Recent studies, based on molecular biology and genetics using Arabidopsis thaliana, have revealed that factors derived from pathogens can modulate host systems and/or host factors that play important roles in the morphological regulation of host plants. Other reports, meanwhile, have shown that factors known to have roles in plant morphology also function in plant immune responses. Evolutionary conservation of these factors and systems implies that host-pathogen interactions and the evolution they drive have yielded tight links between morphological processes and immune responses. In this review, recent findings about these topics are introduced and discussed.

The Granuloma in Tuberculosis: Dynamics of a Host–Pathogen Collusion

PubMed Central

Ehlers, Stefan; Schaible, Ulrich E.

2012-01-01

A granuloma is defined as an inflammatory mononuclear cell infiltrate that, while capable of limiting growth of Mycobacterium tuberculosis, also provides a survival niche from which the bacteria may disseminate. The tuberculosis lesion is highly dynamic and shaped by both, immune response elements and the pathogen. In the granuloma, M. tuberculosis switches to a non-replicating but energy-generating life style whose detailed molecular characterization can identify novel targets for chemotherapy. To secure transmission to a new host, M. tuberculosis has evolved to drive T cell immunity to the point that necrotizing granulomas leak into bronchial cavities to facilitate expectoration of bacilli. From an evolutionary perspective it is therefore questionable whether vaccination and immunity enhancing strategies that merely mimic the natural immune response directed against M. tuberculosis infection can overcome pulmonary tuberculosis in the adult population. Juxtaposition of molecular pathology and immunology with microbial physiology and the use of novel imaging approaches afford an integrative view of the granuloma’s contribution to the life cycle of M. tuberculosis. This review revisits the different input of innate and adaptive immunity in granuloma biogenesis, with a focus on the co-evolutionary forces that redirect immune responses also to the benefit of the pathogen, i.e., its survival, propagation, and transmission. PMID:23308075

Recognition of bacterial plant pathogens: local, systemic and transgenerational immunity.

PubMed

Henry, Elizabeth; Yadeta, Koste A; Coaker, Gitta

2013-09-01

Bacterial pathogens can cause multiple plant diseases and plants rely on their innate immune system to recognize and actively respond to these microbes. The plant innate immune system comprises extracellular pattern recognition receptors that recognize conserved microbial patterns and intracellular nucleotide binding leucine-rich repeat (NLR) proteins that recognize specific bacterial effectors delivered into host cells. Plants lack the adaptive immune branch present in animals, but still afford flexibility to pathogen attack through systemic and transgenerational resistance. Here, we focus on current research in plant immune responses against bacterial pathogens. Recent studies shed light onto the activation and inactivation of pattern recognition receptors and systemic acquired resistance. New research has also uncovered additional layers of complexity surrounding NLR immune receptor activation, cooperation and sub-cellular localizations. Taken together, these recent advances bring us closer to understanding the web of molecular interactions responsible for coordinating defense responses and ultimately resistance. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

The Z Proteins of Pathogenic but Not Nonpathogenic Arenaviruses Inhibit RIG-i-Like Receptor-Dependent Interferon Production

PubMed Central

Xing, Junji; Ly, Hinh

2014-01-01

ABSTRACT Arenavirus pathogens cause a wide spectrum of diseases in humans ranging from central nervous system disease to lethal hemorrhagic fevers with few treatment options. The reason why some arenaviruses can cause severe human diseases while others cannot is unknown. We find that the Z proteins of all known pathogenic arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Lassa, Junin, Machupo, Sabia, Guanarito, Chapare, Dandenong, and Lujo viruses, can inhibit retinoic acid-inducible gene 1 (RIG-i) and Melanoma Differentiation-Associated protein 5 (MDA5), in sharp contrast to those of 14 other nonpathogenic arenaviruses. Inhibition of the RIG-i-like receptors (RLRs) by pathogenic Z proteins is mediated by the protein-protein interactions of Z and RLRs, which lead to the disruption of the interactions between RLRs and mitochondrial antiviral signaling (MAVS). The Z-RLR interactive interfaces are located within the N-terminal domain (NTD) of the Z protein and the N-terminal CARD domains of RLRs. Swapping of the LCMV Z NTD into the nonpathogenic Pichinde virus (PICV) genome does not affect virus growth in Vero cells but significantly inhibits the type I interferon (IFN) responses and increases viral replication in human primary macrophages. In summary, our results show for the first time an innate immune-system-suppressive mechanism shared by the diverse pathogenic arenaviruses and thus shed important light on the pathogenic mechanism of human arenavirus pathogens. IMPORTANCE We show that all known human-pathogenic arenaviruses share an innate immune suppression mechanism that is based on viral Z protein-mediated RLR inhibition. Our report offers important insights into the potential mechanism of arenavirus pathogenesis, provides a convenient way to evaluate the pathogenic potential of known and/or emerging arenaviruses, and reveals a novel target for the development of broad-spectrum therapies to treat this group of diverse pathogens. More broadly, our report provides a better understanding of the mechanisms of viral immune suppression and host-pathogen interactions. PMID:25552708

A systems biology approach to study systemic inflammation.

PubMed

Chen, Bor-Sen; Wu, Chia-Chou

2014-01-01

Systemic inflammation needs a precise control on the sequence and magnitude of occurring events. The high throughput data on the host-pathogen interactions gives us an opportunity to have a glimpse on the systemic inflammation. In this article, a dynamic Candida albicans-zebrafish interactive infectious network is built as an example to demonstrate how systems biology approach can be used to study systematic inflammation. In particular, based on microarray data of C. albicans and zebrafish during infection, the hyphal growth, zebrafish, and host-pathogen intercellular PPI networks were combined to form an integrated infectious PPI network that helps us understand the systematic mechanisms underlying the pathogenicity of C. albicans and the immune response of the host. The signaling pathways for morphogenesis and hyphal growth of C. albicans were 2 significant interactions found in the intercellular PPI network. Two cellular networks were also developed corresponding to the different infection stages (adhesion and invasion), and then compared with each other to identify proteins to gain more insight into the pathogenic role of hyphal development in the C. albicans infection process. Important defense-related proteins in zebrafish were predicted using the same approach. This integrated network consisting of intercellular invasion and cellular defense processes during infection can improve medical therapies and facilitate development of new antifungal drugs.

Drosophila as a model system to unravel the layers of innate immunity to infection

PubMed Central

Kounatidis, Ilias; Ligoxygakis, Petros

2012-01-01

Summary Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens. The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host–pathogen interactions. Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions. PMID:22724070

Drosophila as a model system to unravel the layers of innate immunity to infection.

PubMed

Kounatidis, Ilias; Ligoxygakis, Petros

2012-05-01

Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens. The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host-pathogen interactions. Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions.

An Update on Host-Pathogen Interplay and Modulation of Immune Responses during Orientia tsutsugamushi Infection.

PubMed

Díaz, Fabián E; Abarca, Katia; Kalergis, Alexis M

2018-04-01

The obligate intracellular bacterium Orientia tsutsugamushi is the causative agent of scrub typhus in humans, a serious mite-borne disease present in a widespread area of endemicity, which affects an estimated 1 million people every year. This disease may exhibit a broad range of presentations, ranging from asymptomatic to fatal conditions, with the latter being due to disseminated endothelial infection and organ injury. Unique characteristics of the biology and host-pathogen interactions of O. tsutsugamushi , including the high antigenic diversity among strains and the highly variable, short-lived memory responses developed by the host, underlie difficulties faced in the pursuit of an effective vaccine, which is an imperative need. Other factors that have hindered scientific progress relative to the infectious mechanisms of and the immune response triggered by this bacterium in vertebrate hosts include the limited number of mechanistic studies performed on animal models and the lack of genetic tools currently available for this pathogen. However, recent advances in animal model development are promising to improve our understanding of host-pathogen interactions. Here, we comprehensively discuss the recent advances in and future perspectives on host-pathogen interactions and the modulation of immune responses related to this reemerging disease, highlighting the role of animal models. Copyright © 2018 American Society for Microbiology.

Functional diversification of structurally alike NLR proteins in plants.

PubMed

Chakraborty, Joydeep; Jain, Akansha; Mukherjee, Dibya; Ghosh, Suchismita; Das, Sampa

2018-04-01

In due course of evolution many pathogens alter their effector molecules to modulate the host plants' metabolism and immune responses triggered upon proper recognition by the intracellular nucleotide-binding oligomerization domain containing leucine-rich repeat (NLR) proteins. Likewise, host plants have also evolved with diversified NLR proteins as a survival strategy to win the battle against pathogen invasion. NLR protein indeed detects pathogen derived effector proteins leading to the activation of defense responses associated with programmed cell death (PCD). In this interactive process, genome structure and plasticity play pivotal role in the development of innate immunity. Despite being quite conserved with similar biological functions in all eukaryotes, the intracellular NLR immune receptor proteins happen to be structurally distinct. Recent studies have made progress in identifying transcriptional regulatory complexes activated by NLR proteins. In this review, we attempt to decipher the intracellular NLR proteins mediated surveillance across the evolutionarily diverse taxa, highlighting some of the recent updates on NLR protein compartmentalization, molecular interactions before and after activation along with insights into the finer role of these receptor proteins to combat invading pathogens upon their recognition. Latest information on NLR sensors, helpers and NLR proteins with integrated domains in the context of plant pathogen interactions are also discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Human Milk Blocks DC-SIGN–Pathogen Interaction via MUC1

PubMed Central

Koning, Nathalie; Kessen, Sabine F. M.; Van Der Voorn, J. Patrick; Appelmelk, Ben J.; Jeurink, Prescilla V.; Knippels, Leon M. J.; Garssen, Johan; Van Kooyk, Yvette

2015-01-01

Beneficial effects of breastfeeding are well-recognized and include both immediate neonatal protection against pathogens and long-term protection against allergies and autoimmune diseases. Although several proteins have been identified to have anti-viral or anti-bacterial effects like secretory IgA or lactoferrin, the mechanisms of immune modulation are not fully understood. Recent studies identified important beneficial effects of glycans in human milk, such as those expressed in oligosaccharides or on glycoproteins. Glycans are recognized by the carbohydrate receptors C-type lectins on dendritic cell (DC) and specific tissue macrophages, which exert important functions in immune modulation and immune homeostasis. A well-characterized C-type lectin is dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), which binds terminal fucose. The present study shows that in human milk, MUC1 is the major milk glycoprotein that binds to the lectin domain of DC-SIGN and prevents pathogen interaction through the presence of Lewis x-type oligosaccharides. Surprisingly, this was specific for human milk, as formula, bovine or camel milk did not show any presence of proteins that interacted with DC-SIGN. The expression of DC-SIGN is found in young infants along the entire gastrointestinal tract. Our data thus suggest the importance of human milk glycoproteins for blocking pathogen interaction to DC in young children. Moreover, a potential benefit of human milk later in life in shaping the infants immune system through DC-SIGN cannot be ruled out. PMID:25821450

Host-pathogen interaction in Fusarium oxysporum infections: where do we stand?

PubMed

Husaini, Amjad M; Sakina, Aafreen; Cambay, Souliha R

2018-03-16

Fusarium oxysporum, a ubiquitous soil-borne pathogen causes devastating vascular wilt in more than 100 plant species and ranks fifth among top ten fungal plant pathogens. It has emerged as a human pathogen too, causing infections in immune-compromised patients. It is, therefore, important to gain insight into the molecular processes involved in the pathogenesis of this trans-kingdom pathogen. A complex network comprising of interconnected and over lapping signal pathways; mitogen-activated protein kinase (MAPK) signaling pathways, Ras proteins, G-protein signaling components and their downstream pathways, components of the velvet (LaeA/VeA/VelB) complex and cAMP pathways, is involved in perceiving the host. This network regulates the expression of various pathogenicity genes. Plants have however evolved an elaborate protection system to combat this attack. They too possess intricate mechanisms at molecular level, which once triggered by pathogen attack transduce signals to activate defense response. This review focuses on understanding and presenting a wholistic picture of the molecular mechanisms of F. oxysporum-host interactions in plant immunity.

Myxoma virus in the European rabbit: interactions between the virus and its susceptible host.

PubMed

Stanford, Marianne M; Werden, Steven J; McFadden, Grant

2007-01-01

Myxoma virus (MV) is a poxvirus that evolved in Sylvilagus lagomorphs, and is the causative agent of myxomatosis in European rabbits (Oryctolagus cuniculus). This virus is not a natural pathogen of O. cuniculus, yet is able to subvert the host rabbit immune system defenses and cause a highly lethal systemic infection. The interaction of MV proteins and the rabbit immune system has been an ideal model to help elucidate host/poxvirus interactions, and has led to a greater understanding of how other poxvirus pathogens are able to cause disease in their respective hosts. This review will examine how MV causes myxomatosis, by examining a selection of the identified immunomodulatory proteins that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts.

B cells and their role in the teleost gut

PubMed Central

Korytář, Tomáš; Takizawa, Fumio

2016-01-01

Mucosal surfaces are the main route of entry for pathogens in all living organisms. In the case of teleost fish, mucosal surfaces cover the vast majority of the animal. As these surfaces are in constant contact with the environment, fish are perpetually exposed to a vast number of pathogens. Despite the potential prevalence and variety of pathogens, mucosal surfaces are primarily populated by commensal non-pathogenic bacteria. Indeed, a fine balance between these two populations of microorganisms is crucial for animal survival. This equilibrium, controlled by the mucosal immune system, maintains homeostasis at mucosal tissues. Teleost fish possess a diffuse mucosa-associated immune system in the intestine, with B cells being one of the main responders. Immunoglobulins produced by these lymphocytes are a critical line of defense against pathogens and also prevent the entrance of commensal bacteria into the epithelium. In this review we will summarize recent literature regarding the role of B-lymphocytes and immunoglobulins in gut immunity in teleost fish, with specific focus on immunoglobulin isotypes and the microorganisms, pathogenic and non-pathogenic that interact with the immune system. PMID:26995768

Immunity in urogenital protozoa.

PubMed

Malla, N; Goyal, K; Dhanda, R S; Yadav, M

2014-09-01

Innate and adaptive immunity play a significant role in urogenital infections. Innate immunity is provided by the epithelial cells and mucus lining along with acidic pH, which forms a strong physical barrier against the pathogens in female reproductive tract. Cells of innate immune system, antimicrobial peptides, cytokines, chemokines and adaptive immunity in the reproductive tract are evolved during infection, and a pro-inflammatory response is generated to fight against the invading pathogen Trichomonas vaginalis, a primary urogenital protozoa, the etiological agent of human trichomoniasis, a curable sexually transmitted infection. The involvement of the urogenital tract by other protozoal infections such as P. falciparum, Trypanosoma, Leishmania, Toxoplasma, Entamoeba histolytica and Acanthamoeba infection is rarely reported. Trichomonas induce pro-inflammatory and immunosuppressive responses in infected subjects. Multifactorial pathogenic mechanisms including parasite adherence, cysteine proteases, lipophosphoglycan, free radical, cytokine generation and Toll-like receptors appear to interplay with the induction of local and systemic immune responses that ultimately determine the outcome of the infection. However, the involvement of urogenital pathogen-specific immune mechanisms and effect of normal local resident flora on the outcome (symptomatic vs. asymptomatic) of infection are poorly understood. Moreover, immune interactions in trichomoniasis subjects co-infected with bacterial and viral pathogens need to be elucidated. © 2014 John Wiley & Sons Ltd.

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants.

PubMed

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants.

Bioassays for assessing jasmonate-dependent defenses triggered by pathogens, herbivorous insects, or beneficial rhizobacteria.

PubMed

Van Wees, Saskia C M; Van Pelt, Johan A; Bakker, Peter A H M; Pieterse, Corné M J

2013-01-01

Jasmonates, together with other plant hormones, are important orchestrators of the plant immune system. The different hormone-controlled signaling pathways cross-communicate in an antagonistic or a synergistic manner, providing the plant with a powerful capacity to finely regulate its immune response. Jasmonic acid (JA) signaling is required for plant resistance to harmful organisms, such as necrotrophic pathogens and herbivorous insects. Furthermore, JA signaling is essential in interactions of plants with beneficial microbes that induce systemic resistance to pathogens and insects. The role of JA signaling components in plant immunity can be studied by performing bioassays with different interacting organisms. Determination of the level of resistance and the induction of defense responses in plants with altered JA components, through mutation or ectopic expression, will unveil novel mechanisms of JA signaling. We provide detailed protocols of bioassays with the model plant Arabidopsis thaliana challenged with the pathogens Botrytis cinerea and Pseudomonas syringae, the insect herbivore Pieris rapae, and the beneficial microbe Pseudomonas fluorescens. In addition, we describe pharmacological assays to study the modulation of JA-regulated responses by exogenous application of combinations of hormones, because a simultaneous rise in hormone levels occurs during interaction of plants with other organisms.

Yersinia vs. host Immunity: how a pathogen evades or triggers a protective response

PubMed Central

Chung, Lawton K.; Bliska, James B.

2015-01-01

The human pathogenic Yersinia species cause diseases that represent a significant source of morbidity and mortality. Despite this, specific mechanisms underlying Yersinia pathogenesis and protective host responses remain poorly understood. Recent studies have shown that Yersinia disrupt cell death pathways, perturb inflammatory processes and exploit immune cells to promote disease. The ensuing host responses following Yersinia infection include coordination of innate and adaptive immune responses in an attempt to control bacterial replication. Here, we highlight current advances in our understanding of the interactions between the pathogenic yersiniae and host cells, as well as the protective host responses mobilized to counteract these pathogens. Together, these studies enhance our understanding of Yersinia pathogenesis and highlight the ongoing battle between host and microbe. PMID:26638030

Interplay Between Innate Immunity and the Plant Microbiota.

PubMed

Hacquard, Stéphane; Spaepen, Stijn; Garrido-Oter, Ruben; Schulze-Lefert, Paul

2017-08-04

The innate immune system of plants recognizes microbial pathogens and terminates their growth. However, recent findings suggest that at least one layer of this system is also engaged in cooperative plant-microbe interactions and influences host colonization by beneficial microbial communities. This immune layer involves sensing of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) that initiate quantitative immune responses to control host-microbial load, whereas diversification of MAMPs and PRRs emerges as a mechanism that locally sculpts microbial assemblages in plant populations. This suggests a more complex microbial management role of the innate immune system for controlled accommodation of beneficial microbes and in pathogen elimination. The finding that similar molecular strategies are deployed by symbionts and pathogens to dampen immune responses is consistent with this hypothesis but implies different selective pressures on the immune system due to contrasting outcomes on plant fitness. The reciprocal interplay between microbiota and the immune system likely plays a critical role in shaping beneficial plant-microbiota combinations and maintaining microbial homeostasis.

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection.

PubMed

Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M; Casadevall, Arturo; Flynn, JoAnne

2014-12-01

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection

PubMed Central

Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M.; Casadevall, Arturo; Flynn, JoAnne

2014-01-01

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. PMID:25458990

Responses to a warming world: Integrating life history, immune investment, and pathogen resistance in a model insect species.

PubMed

Laughton, Alice M; O'Connor, Cian O; Knell, Robert J

2017-11-01

Environmental temperature has important effects on the physiology and life history of ectothermic animals, including investment in the immune system and the infectious capacity of pathogens. Numerous studies have examined individual components of these complex systems, but little is known about how they integrate when animals are exposed to different temperatures. Here, we use the Indian meal moth ( Plodia interpunctella ) to understand how immune investment and disease resistance react and potentially trade-off with other life-history traits. We recorded life-history (development time, survival, fecundity, and body size) and immunity (hemocyte counts, phenoloxidase activity) measures and tested resistance to bacterial ( E. coli ) and viral ( Plodia interpunctella granulosis virus) infection at five temperatures (20-30°C). While development time, lifespan, and size decreased with temperature as expected, moths exhibited different reproductive strategies in response to small changes in temperature. At cooler temperatures, oviposition rates were low but tended to increase toward the end of life, whereas warmer temperatures promoted initially high oviposition rates that rapidly declined after the first few days of adult life. Although warmer temperatures were associated with strong investment in early reproduction, there was no evidence of an associated trade-off with immune investment. Phenoloxidase activity increased most at cooler temperatures before plateauing, while hemocyte counts increased linearly with temperature. Resistance to bacterial challenge displayed a complex pattern, whereas survival after a viral challenge increased with rearing temperature. These results demonstrate that different immune system components and different pathogens can respond in distinct ways to changes in temperature. Overall, these data highlight the scope for significant changes in immunity, disease resistance, and host-parasite population dynamics to arise from small, biologically relevant changes to environmental temperature. In light of global warming, understanding these complex interactions is vital for predicting the potential impact of insect disease vectors and crop pests on public health and food security.

Enteric pathogens and gut function: role of cytokines and STATs

USDA-ARS?s Scientific Manuscript database

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against pathogens. In response to the invasion of various pathogens, naïve CD4+ cells differenti...

An anti-DNA antibody prefers damaged dsDNA over native.

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2017-01-01

DNA-protein interactions, including DNA-antibody complexes, have both fundamental and practical significance. In particular, antibodies against double-stranded DNA play an important role in the pathogenesis of autoimmune diseases. Elucidation of structural mechanisms of an antigen recognition and interaction of anti-DNA antibodies provides a basis for understanding the role of DNA-containing immune complexes in human pathologies and for new treatments. Here we used Molecular Dynamic simulations of bimolecular complexes of a segment of dsDNA with a monoclonal anti-DNA antibody's Fab-fragment to obtain detailed structural and physical characteristics of the dynamic intermolecular interactions. Using a computationally modified crystal structure of a Fab-DNA complex (PDB: 3VW3), we studied in silico equilibrium Molecular Dynamics of the Fab-fragment associated with two homologous dsDNA fragments, containing or not containing dimerized thymine, a product of DNA photodamage. The Fab-fragment interactions with the thymine dimer-containing DNA was thermodynamically more stable than with the native DNA. The amino acid residues constituting a paratope and the complementary nucleotide epitopes for both Fab-DNA constructs were identified. Stacking and electrostatic interactions were shown to play the main role in the antibody-dsDNA contacts, while hydrogen bonds were less significant. The aggregate of data show that the chemically modified dsDNA (containing a covalent thymine dimer) has a higher affinity toward the antibody and forms a stronger immune complex. These findings provide a mechanistic insight into formation and properties of the pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus, associated with skin photosensibilization and DNA photodamage.

Infection dynamic of symbiotic bacteria in the pea aphid Acyrthosiphon pisum gut and host immune response at the early steps in the infection process.

PubMed

Renoz, François; Noël, Christine; Errachid, Abdelmounaim; Foray, Vincent; Hance, Thierry

2015-01-01

In addition to its obligatory symbiont Buchnera aphidicola, the pea aphid Acyrthosiphon pisum can harbor several facultative bacterial symbionts which can be mutualistic in the context of various ecological interactions. Belonging to a genus where many members have been described as pathogen in invertebrates, Serratia symbiotica is one of the most common facultative partners found in aphids. The recent discovery of strains able to grow outside their host allowed us to simulate environmental acquisition of symbiotic bacteria by aphids. Here, we performed an experiment to characterize the A. pisum response to the ingestion of the free-living S. symbiotica CWBI-2.3T in comparison to the ingestion of the pathogenic Serratia marcescens Db11 at the early steps in the infection process. We found that, while S. marcescens Db11 killed the aphids within a few days, S. symbiotica CWBI-2.3T did not affect host survival and colonized the whole digestive tract within a few days. Gene expression analysis of immune genes suggests that S. symbiotica CWBI-2.3T did not trigger an immune reaction, while S. marcescens Db11 did, and supports the hypothesis of a fine-tuning of the host immune response set-up for fighting pathogens while maintaining mutualistic partners. Our results also suggest that the lysosomal system and the JNK pathway are possibly involved in the regulation of invasive bacteria in aphids and that the activation of the JNK pathway is IMD-independent in the pea aphid.

Infection Dynamic of Symbiotic Bacteria in the Pea Aphid Acyrthosiphon pisum Gut and Host Immune Response at the Early Steps in the Infection Process

PubMed Central

Renoz, François; Noël, Christine; Errachid, Abdelmounaim; Foray, Vincent; Hance, Thierry

2015-01-01

In addition to its obligatory symbiont Buchnera aphidicola, the pea aphid Acyrthosiphon pisum can harbor several facultative bacterial symbionts which can be mutualistic in the context of various ecological interactions. Belonging to a genus where many members have been described as pathogen in invertebrates, Serratia symbiotica is one of the most common facultative partners found in aphids. The recent discovery of strains able to grow outside their host allowed us to simulate environmental acquisition of symbiotic bacteria by aphids. Here, we performed an experiment to characterize the A. pisum response to the ingestion of the free-living S. symbiotica CWBI-2.3T in comparison to the ingestion of the pathogenic Serratia marcescens Db11 at the early steps in the infection process. We found that, while S. marcescens Db11 killed the aphids within a few days, S. symbiotica CWBI-2.3T did not affect host survival and colonized the whole digestive tract within a few days. Gene expression analysis of immune genes suggests that S. symbiotica CWBI-2.3T did not trigger an immune reaction, while S. marcescens Db11 did, and supports the hypothesis of a fine-tuning of the host immune response set-up for fighting pathogens while maintaining mutualistic partners. Our results also suggest that the lysosomal system and the JNK pathway are possibly involved in the regulation of invasive bacteria in aphids and that the activation of the JNK pathway is IMD-independent in the pea aphid. PMID:25811863

Inflammation in acute and chronic pancreatitis.

PubMed

Habtezion, Aida

2015-09-01

This report reviews recent animal model and human studies associated with inflammatory responses in acute and chronic pancreatitis. Animal model and limited human acute and chronic pancreatitis studies unravel the dynamic nature of the inflammatory processes and the ability of the immune cells to sense danger and environmental signals. In acute pancreatitis, such molecules include pathogen-associated molecular pattern recognition receptors such as toll-like receptors, and the more recently appreciated damage-associated molecular pattern molecules or 'alarmin' high mobility group box 1 and IL-33. In chronic pancreatitis, a recent understanding of a critical role for macrophage-pancreatic stellate cell interaction offers a potential targetable pathway that can alter fibrogenesis. Microbiome research in pancreatitis is a new field gaining interest but will require further investigation. Immune cell contribution to the pathogenesis of acute and chronic pancreatitis is gaining more appreciation and further understanding in immune signaling presents potential therapeutic targets that can alter disease progression.

Time and dose-dependent risk of pneumococcal pneumonia following influenza: a model for within-host interaction between influenza and Streptococcus pneumoniae

PubMed Central

Shrestha, Sourya; Foxman, Betsy; Dawid, Suzanne; Aiello, Allison E.; Davis, Brian M.; Berus, Joshua; Rohani, Pejman

2013-01-01

A significant fraction of seasonal and in particular pandemic influenza deaths are attributed to secondary bacterial infections. In animal models, influenza virus predisposes hosts to severe infection with both Streptococcus pneumoniae and Staphylococcus aureus. Despite its importance, the mechanistic nature of the interaction between influenza and pneumococci, its dependence on the timing and sequence of infections as well as the clinical and epidemiological consequences remain unclear. We explore an immune-mediated model of the viral–bacterial interaction that quantifies the timing and the intensity of the interaction. Taking advantage of the wealth of knowledge gained from animal models, and the quantitative understanding of the kinetics of pathogen-specific immunological dynamics, we formulate a mathematical model for immune-mediated interaction between influenza virus and S. pneumoniae in the lungs. We use the model to examine the pathogenic effect of inoculum size and timing of pneumococcal invasion relative to influenza infection, as well as the efficacy of antivirals in preventing severe pneumococcal disease. We find that our model is able to capture the key features of the interaction observed in animal experiments. The model predicts that introduction of pneumococcal bacteria during a 4–6 day window following influenza infection results in invasive pneumonia at significantly lower inoculum size than in hosts not infected with influenza. Furthermore, we find that antiviral treatment administered later than 4 days after influenza infection was not able to prevent invasive pneumococcal disease. This work provides a quantitative framework to study interactions between influenza and pneumococci and has the potential to accurately quantify the interactions. Such quantitative understanding can form a basis for effective clinical care, public health policies and pandemic preparedness. PMID:23825111

Recent progress in the understanding of host immunity to avian coccidiosis: IL-17 family cytokines as the sentinels on the intestinal mucosa

USDA-ARS?s Scientific Manuscript database

Host-pathogen interaction leading to protection against coccidiosis is complex, involving many aspects of innate and adaptive immunity to intracellular parasites. Innate immunity is mediated by various subpopulations of innate immune cells through the secretion of soluble factors with diverse functi...

A comparative study of an innate immune response in Lamprologine cichlid fishes.

PubMed

O'Connor, Constance M; Reddon, Adam R; Marsh-Rollo, Susan E; Hellmann, Jennifer K; Ligocki, Isaac Y; Hamilton, Ian M; Balshine, Sigal

2014-10-01

Social interactions facilitate pathogen transmission and increase virulence. Therefore, species that live in social groups are predicted to suffer a higher pathogen burden, to invest more heavily in immune defence against pathogens, or both. However, there are few empirical tests of whether social species indeed invest more heavily in immune defence than non-social species. In the current study, we conducted a phylogenetically controlled comparison of innate immune response in Lamprologine cichlid fishes. We focused on three species of highly social cichlids that live in permanent groups and exhibit cooperative breeding (Julidochromis ornatus, Neolamprologus pulcher and Neolamprologus savoryi) and three species of non-social cichlids that exhibit neither grouping nor cooperative behaviour (Telmatochromis temporalis, Neolamprologus tetracanthus and Neolamprologus modestus). We quantified the innate immune response by injecting wild fishes with phytohaemagglutinin (PHA), a lectin that causes a cell-mediated immune response. We predicted that the three highly social species would show a greater immune reaction to the PHA treatment, indicating higher investment in immune defence against parasites relative to the three non-social species. We found significant species-level variation in immune response, but contrary to our prediction, this variation did not correspond to social system. However, we found that immune response was correlated with territory size across the six species. Our results indicate that the common assumption of a positive relationship between social system and investment in immune function may be overly simplistic. We suggest that factors such as rates of both in-group and out-group social interactions are likely to be important mediators of the relationship between sociality and immune function.

A comparative study of an innate immune response in Lamprologine cichlid fishes

NASA Astrophysics Data System (ADS)

O'Connor, Constance M.; Reddon, Adam R.; Marsh-Rollo, Susan E.; Hellmann, Jennifer K.; Ligocki, Isaac Y.; Hamilton, Ian M.; Balshine, Sigal

2014-10-01

Social interactions facilitate pathogen transmission and increase virulence. Therefore, species that live in social groups are predicted to suffer a higher pathogen burden, to invest more heavily in immune defence against pathogens, or both. However, there are few empirical tests of whether social species indeed invest more heavily in immune defence than non-social species. In the current study, we conducted a phylogenetically controlled comparison of innate immune response in Lamprologine cichlid fishes. We focused on three species of highly social cichlids that live in permanent groups and exhibit cooperative breeding ( Julidochromis ornatus, Neolamprologus pulcher and Neolamprologus savoryi) and three species of non-social cichlids that exhibit neither grouping nor cooperative behaviour ( Telmatochromis temporalis, Neolamprologus tetracanthus and Neolamprologus modestus). We quantified the innate immune response by injecting wild fishes with phytohaemagglutinin (PHA), a lectin that causes a cell-mediated immune response. We predicted that the three highly social species would show a greater immune reaction to the PHA treatment, indicating higher investment in immune defence against parasites relative to the three non-social species. We found significant species-level variation in immune response, but contrary to our prediction, this variation did not correspond to social system. However, we found that immune response was correlated with territory size across the six species. Our results indicate that the common assumption of a positive relationship between social system and investment in immune function may be overly simplistic. We suggest that factors such as rates of both in-group and out-group social interactions are likely to be important mediators of the relationship between sociality and immune function.

Activation of the RLR/MAVS Signaling Pathway by the L Protein of Mopeia Virus

PubMed Central

Zhang, Lei-Ke; Xin, Qi-Lin; Zhu, Sheng-Lin; Wan, Wei-Wei; Wang, Wei

2016-01-01

ABSTRACT The family Arenaviridae includes several important human pathogens that can cause severe hemorrhagic fever and greatly threaten public health. As a major component of the innate immune system, the RLR/MAVS signaling pathway is involved in recognizing viral components and initiating antiviral activity. It has been reported that arenavirus infection can suppress the innate immune response, and NP and Z proteins of pathogenic arenaviruses can disrupt RLR/MAVS signaling, thus inhibiting production of type I interferon (IFN-I). However, recent studies have shown elevated IFN-I levels in certain arenavirus-infected cells. The mechanism by which arenavirus infection induces IFN-I responses remains unclear. In this study, we determined that the L polymerase (Lp) of Mopeia virus (MOPV), an Old World (OW) arenavirus, can activate the RLR/MAVS pathway and thus induce the production of IFN-I. This activation is associated with the RNA-dependent RNA polymerase activity of Lp. This study provides a foundation for further studies of interactions between arenaviruses and the innate immune system and for the elucidation of arenavirus pathogenesis. IMPORTANCE Distinct innate immune responses are observed when hosts are infected with different arenaviruses. It has been widely accepted that NP and certain Z proteins of arenaviruses inhibit the RLR/MAVS signaling pathway. The viral components responsible for the activation of the RLR/MAVS signaling pathway remain to be determined. In the current study, we demonstrate for the first time that the Lp of MOPV, an OW arenavirus, can activate the RLR/MAVS signaling pathway and thus induce the production of IFN-I. Based on our results, we proposed that dynamic interactions exist among Lp-produced RNA, NP, and the RLR/MAVS signaling pathway, and the outcome of these interactions may determine the final IFN-I response pattern: elevated or reduced. Our study provides a possible explanation for how IFN-I can become activated during arenavirus infection and may help us gain insights into the interactions that form between different arenavirus components and the innate immune system. PMID:27605671

Interaction of the tick immune system with transmitted pathogens

PubMed Central

Hajdušek, Ondřej; Šíma, Radek; Ayllón, Nieves; Jalovecká, Marie; Perner, Jan; de la Fuente, José; Kopáček, Petr

2013-01-01

Ticks are hematophagous arachnids transmitting a wide variety of pathogens including viruses, bacteria, and protozoans to their vertebrate hosts. The tick vector competence has to be intimately linked to the ability of transmitted pathogens to evade tick defense mechanisms encountered on their route through the tick body comprising midgut, hemolymph, salivary glands or ovaries. Tick innate immunity is, like in other invertebrates, based on an orchestrated action of humoral and cellular immune responses. The direct antimicrobial defense in ticks is accomplished by a variety of small molecules such as defensins, lysozymes or by tick-specific antimicrobial compounds such as microplusin/hebraein or 5.3-kDa family proteins. Phagocytosis of the invading microbes by tick hemocytes is likely mediated by the primordial complement-like system composed of thioester-containing proteins, fibrinogen-related lectins and convertase-like factors. Moreover, an important role in survival of the ingested microbes seems to be played by host proteins and redox balance maintenance in the tick midgut. Here, we summarize recent knowledge about the major components of tick immune system and focus on their interaction with the relevant tick-transmitted pathogens, represented by spirochetes (Borrelia), rickettsiae (Anaplasma), and protozoans (Babesia). Availability of the tick genomic database and feasibility of functional genomics based on RNA interference greatly contribute to the understanding of molecular and cellular interplay at the tick-pathogen interface and may provide new targets for blocking the transmission of tick pathogens. PMID:23875177

Convergent Evolution of Pathogen Effectors toward Reactive Oxygen Species Signaling Networks in Plants

PubMed Central

Jwa, Nam-Soo; Hwang, Byung Kook

2017-01-01

Microbial pathogens have evolved protein effectors to promote virulence and cause disease in host plants. Pathogen effectors delivered into plant cells suppress plant immune responses and modulate host metabolism to support the infection processes of pathogens. Reactive oxygen species (ROS) act as cellular signaling molecules to trigger plant immune responses, such as pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and effector-triggered immunity. In this review, we discuss recent insights into the molecular functions of pathogen effectors that target multiple steps in the ROS signaling pathway in plants. The perception of PAMPs by pattern recognition receptors leads to the rapid and strong production of ROS through activation of NADPH oxidase Respiratory Burst Oxidase Homologs (RBOHs) as well as peroxidases. Specific pathogen effectors directly or indirectly interact with plant nucleotide-binding leucine-rich repeat receptors to induce ROS production and the hypersensitive response in plant cells. By contrast, virulent pathogens possess effectors capable of suppressing plant ROS bursts in different ways during infection. PAMP-triggered ROS bursts are suppressed by pathogen effectors that target mitogen-activated protein kinase cascades. Moreover, pathogen effectors target vesicle trafficking or metabolic priming, leading to the suppression of ROS production. Secreted pathogen effectors block the metabolic coenzyme NADP-malic enzyme, inhibiting the transfer of electrons to the NADPH oxidases (RBOHs) responsible for ROS generation. Collectively, pathogen effectors may have evolved to converge on a common host protein network to suppress the common plant immune system, including the ROS burst and cell death response in plants. PMID:29033963

DNA Methylation and Demethylation in Plant Immunity.

PubMed

Deleris, A; Halter, T; Navarro, L

2016-08-04

Detection of plant and animal pathogens triggers a massive transcriptional reprogramming, which is directed by chromatin-based processes, and ultimately results in antimicrobial immunity. Although the implication of histone modifications in orchestrating biotic stress-induced transcriptional reprogramming has been well characterized, very little was known, until recently, about the role of DNA methylation and demethylation in this process. In this review, we summarize recent findings on the dynamics and biological relevance of DNA methylation and demethylation in plant immunity against nonviral pathogens. In particular, we report the implications of these epigenetic regulatory processes in the transcriptional and co-transcriptional control of immune-responsive genes and discuss their relevance in fine-tuning antimicrobial immune responses. Finally, we discuss the possible yet elusive role of DNA methylation and demethylation in systemic immune responses, transgenerational immune priming, and de novo epiallelism, which could be adaptive.

Interaction of human, rat, and mouse immunoglobulin A (IgA) with Staphylococcal superantigen-like 7 (SSL7) decoy protein and leukocyte IgA receptor.

PubMed

Wines, Bruce D; Ramsland, Paul A; Trist, Halina M; Gardam, Sandra; Brink, Robert; Fraser, John D; Hogarth, P Mark

2011-09-23

Host survival depends on an effective immune system and pathogen survival on the effectiveness of immune evasion mechanisms. Staphylococcus aureus utilizes a number of molecules to modulate host immunity, including the SSL family of which SSL7 binds IgA and inhibits Fcα receptor I (FcαRI)-mediated function. Other Gram-positive bacterial pathogens produce IgA binding proteins, which, similar to SSL7, also bind the Fc at the CH2/CH3 interface (the junction between constant domains 2 and 3 of the heavy chain). The opposing activities of the host FcαRI-IgA receptor ligand pair and the pathogen decoy proteins select for host and pathogen variants, which exert stronger protection or evasion, respectively. Curiously, mouse but not rat IgA contains a putative N-linked glycosylation site in the center of this host receptor and pathogen-binding site. Here, we demonstrate that this site is glycosylated and that the effect of amino acid changes and glycosylation of the CH2/CH3 interface inhibits interaction with the pathogen IgA binding protein SSL7, while maintaining binding of pIgR, essential to the biosynthesis and transport of SIgA.

Bacillus anthracis Interacts with Plasmin(ogen) to Evade C3b-Dependent Innate Immunity

PubMed Central

Chung, Myung-Chul; Tonry, Jessica H.; Narayanan, Aarthi; Manes, Nathan P.; Mackie, Ryan S.; Gutting, Bradford; Mukherjee, Dhritiman V.; Popova, Taissia G.; Kashanchi, Fatah; Bailey, Charles L.; Popov, Serguei G.

2011-01-01

The causative agent of anthrax, Bacillus anthracis, is capable of circumventing the humoral and innate immune defense of the host and modulating the blood chemistry in circulation to initiate a productive infection. It has been shown that the pathogen employs a number of strategies against immune cells using secreted pathogenic factors such as toxins. However, interference of B. anthracis with the innate immune system through specific interaction of the spore surface with host proteins such as the complement system has heretofore attracted little attention. In order to assess the mechanisms by which B. anthracis evades the defense system, we employed a proteomic analysis to identify human serum proteins interacting with B. anthracis spores, and found that plasminogen (PLG) is a major surface-bound protein. PLG efficiently bound to spores in a lysine- and exosporium-dependent manner. We identified α-enolase and elongation factor tu as PLG receptors. PLG-bound spores were capable of exhibiting anti-opsonic properties by cleaving C3b molecules in vitro and in rabbit bronchoalveolar lavage fluid, resulting in a decrease in macrophage phagocytosis. Our findings represent a step forward in understanding the mechanisms involved in the evasion of innate immunity by B. anthracis through recruitment of PLG resulting in the enhancement of anti-complement and anti-opsonization properties of the pathogen. PMID:21464960

Innate scavenger receptor-A regulates adaptive T helper cell responses to pathogen infection

PubMed Central

Xu, Zhipeng; Xu, Lei; Li, Wei; Jin, Xin; Song, Xian; Chen, Xiaojun; Zhu, Jifeng; Zhou, Sha; Li, Yong; Zhang, Weiwei; Dong, Xiaoxiao; Yang, Xiaowei; Liu, Feng; Bai, Hui; Chen, Qi; Su, Chuan

2017-01-01

The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. However, little is known about the role of SR-A in the host adaptive immune responses to pathogen infection. Here we show with mouse models of helminth Schistosoma japonicum infection and heat-inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by pathogens and suppresses IRF5 nuclear translocation by direct interaction. Reduced abundance of nuclear IRF5 shifts macrophage polarization from M1 towards M2, which subsequently switches T-helper responses from type 1 to type 2. Our study identifies a role for SR-A as an innate PRR in regulating adaptive immune responses. PMID:28695899

Yersinia versus host immunity: how a pathogen evades or triggers a protective response.

PubMed

Chung, Lawton K; Bliska, James B

2016-02-01

The human pathogenic Yersinia species cause diseases that represent a significant source of morbidity and mortality. Despite this, specific mechanisms underlying Yersinia pathogenesis and protective host responses remain poorly understood. Recent studies have shown that Yersinia disrupt cell death pathways, perturb inflammatory processes and exploit immune cells to promote disease. The ensuing host responses following Yersinia infection include coordination of innate and adaptive immune responses in an attempt to control bacterial replication. Here, we highlight current advances in our understanding of the interactions between the pathogenic yersiniae and host cells, as well as the protective host responses mobilized to counteract these pathogens. Together, these studies enhance our understanding of Yersinia pathogenesis and highlight the ongoing battle between host and microbe. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of antibodies on pathogen dynamics with delays and two routes of infection

NASA Astrophysics Data System (ADS)

Elaiw, A. M.; Almatrafi, A. A.; Hobiny, A. D.

2018-06-01

We study the global stability of pathogen dynamics models with saturated pathogen-susceptible and infected-susceptible incidence. The models incorporate antibody immune response and three types of discrete or distributed time delays. We first show that the solutions of the model are nonnegative and ultimately bounded. We determine two threshold parameters, the basic reproduction number and antibody response activation number. We establish the existence and stability of the steady states. We study the global stability analysis of models using Lyapunov method. The numerical simulations have shown that antibodies can reduce the pathogen progression.

Chloroplastic protein NRIP1 mediates innate immune receptor recognition of a viral effector

PubMed Central

Caplan, Jeffrey L.; Mamillapalli, Padmavathi; Burch-Smith, Tessa M.; Czymmek, Kirk; Dinesh-Kumar, S.P.

2008-01-01

Summary Plant innate immunity relies on the recognition of pathogen effector molecules by nucleotide-binding-leucine-rich repeat (NB-LRR) immune receptor families. Previously we have shown the N immune receptor, a member of TIR-NB-LRR family, indirectly recognizes the 50-kDa helicase (p50) domain of Tobacco mosaic virus (TMV) through its TIR domain. We have identified an N receptor-interacting protein, NRIP1, that directly interacts with both N's TIR domain and p50. NRIP1 is a functional rhodanese sulfurtransferase and is required for N to provide complete resistance to TMV. Interestingly, NRIP1 that normally localizes to the chloroplasts is recruited to the cytoplasm and nucleus by the p50 effector. As a consequence, NRIP1 interacts with N only in the presence of the p50 effector. Our findings show that a chloroplastic protein is intimately involved in pathogen recognition. We propose that N's activation requires a pre-recognition complex containing the p50 effector and NRIP1. PMID:18267075

Nuclear processes associated with plant immunity and pathogen susceptibility

PubMed Central

Motion, Graham B.; Amaro, Tiago M.M.M.; Kulagina, Natalja

2015-01-01

Plants are sessile organisms that have evolved exquisite and sophisticated mechanisms to adapt to their biotic and abiotic environment. Plants deploy receptors and vast signalling networks to detect, transmit and respond to a given biotic threat by inducing properly dosed defence responses. Genetic analyses and, more recently, next-generation -omics approaches have allowed unprecedented insights into the mechanisms that drive immunity. Similarly, functional genomics and the emergence of pathogen genomes have allowed reciprocal studies on the mechanisms governing pathogen virulence and host susceptibility, collectively allowing more comprehensive views on the processes that govern disease and resistance. Among others, the identification of secreted pathogen molecules (effectors) that modify immunity-associated processes has changed the plant–microbe interactions conceptual landscape. Effectors are now considered both important factors facilitating disease and novel probes, suited to study immunity in plants. In this review, we will describe the various mechanisms and processes that take place in the nucleus and help regulate immune responses in plants. Based on the premise that any process required for immunity could be targeted by pathogen effectors, we highlight and describe a number of functional assays that should help determine effector functions and their impact on immune-related processes. The identification of new effector functions that modify nuclear processes will help dissect nuclear signalling further and assist us in our bid to bolster immunity in crop plants. PMID:25846755

Nuclear processes associated with plant immunity and pathogen susceptibility.

PubMed

Motion, Graham B; Amaro, Tiago M M M; Kulagina, Natalja; Huitema, Edgar

2015-07-01

Plants are sessile organisms that have evolved exquisite and sophisticated mechanisms to adapt to their biotic and abiotic environment. Plants deploy receptors and vast signalling networks to detect, transmit and respond to a given biotic threat by inducing properly dosed defence responses. Genetic analyses and, more recently, next-generation -omics approaches have allowed unprecedented insights into the mechanisms that drive immunity. Similarly, functional genomics and the emergence of pathogen genomes have allowed reciprocal studies on the mechanisms governing pathogen virulence and host susceptibility, collectively allowing more comprehensive views on the processes that govern disease and resistance. Among others, the identification of secreted pathogen molecules (effectors) that modify immunity-associated processes has changed the plant-microbe interactions conceptual landscape. Effectors are now considered both important factors facilitating disease and novel probes, suited to study immunity in plants. In this review, we will describe the various mechanisms and processes that take place in the nucleus and help regulate immune responses in plants. Based on the premise that any process required for immunity could be targeted by pathogen effectors, we highlight and describe a number of functional assays that should help determine effector functions and their impact on immune-related processes. The identification of new effector functions that modify nuclear processes will help dissect nuclear signalling further and assist us in our bid to bolster immunity in crop plants. © The Author 2015. Published by Oxford University Press.

The molecular basis of bacterial-insect symbiosis.

PubMed

Douglas, Angela E

2014-11-25

Insects provide experimentally tractable and cost-effective model systems to investigate the molecular basis of animal-bacterial interactions. Recent research is revealing the central role of the insect innate immune system, especially anti-microbial peptides and reactive oxygen species, in regulating the abundance and composition of the microbiota in various insects, including Drosophila and the mosquitoes Aedes and Anopheles. Interactions between the immune system and microbiota are, however, bidirectional with evidence that members of the resident microbiota can promote immune function, conferring resistance to pathogens and parasites by both activation of immune effectors and production of toxins. Antagonistic and mutualistic interactions among bacteria have also been implicated as determinants of the microbiota composition, including exclusion of pathogens, but the molecular mechanisms are largely unknown. Some bacteria are crucial for insect nutrition, through provisioning of specific nutrients (e.g., B vitamins, essential amino acids) and modulation of the insect nutritional sensing and signaling pathways (e.g., insulin signaling) that regulate nutrient allocation, especially to lipid and other energy reserves. A key challenge for future research is to identify the molecular interaction between specific bacterial effectors and animal receptors, as well as to determine how these interactions translate into microbiota-dependent signaling, metabolism, and immune function in the host. Copyright © 2014. Published by Elsevier Ltd.

Root assays to study pattern-triggered immunity in plant-nematode interactions

USDA-ARS?s Scientific Manuscript database

Plants employ extracellular immune receptors to perceive conserved pathogen-associated molecular patterns (PAMPs), triggering the first layer of defense known as pattern-triggered immunity (PTI). The understanding of PTI is mainly based on the studies focusing on leaves. Plants are vulnerable to att...

Mapping the microbiome of Ictalurid catfish: tissue and species-specific community composition

USDA-ARS?s Scientific Manuscript database

Host mucosal immunity is regulated by the complex interplay between environmental factors, host genetics, and commensal and pathogen dynamics. Microbial imbalances due to physiological stressors, changes in nutrition, and/or antibiotic application can potentiate over-exuberant host immune responses ...

Enteric pathogens and gut function: Role of cytokines and STATs.

PubMed

Shea-Donohue, Terez; Fasano, Alessio; Smith, Allen; Zhao, Aiping

2010-09-01

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against the pathogens. In response to the invasion of various pathogens, naïve CD4(+) cells differentiate into subsets of T helper (Th) cells that are characterized by different cytokine profiles. Cytokines bind to cell surface receptors on both immune and non-immune cells leading to activation of JAK-STAT signaling pathway and influence gut function by upregulating the expression of specific target genes. This review considers the roles of cytokines and receptor-mediated activation of STATs on pathogen-induced changes in gut function. The focus on STAT4 and STAT6 is because of their requirement for the full development of Th1 and Th2 cytokine profiles.

Enteric pathogens and gut function: Role of cytokines and STATs

PubMed Central

Fasano, Alessio; Smith, Allen; Zhao, Aiping

2010-01-01

The gut harbors the largest immune system in the body. The mucosa is considered to be the initial site of interaction with commensal and pathogenic organisms; therefore, it is the first line of defense against the pathogens. In response to the invasion of various pathogens, naïve CD4+ cells differentiate into subsets of T helper (Th) cells that are characterized by different cytokine profiles. Cytokines bind to cell surface receptors on both immune and non-immune cells leading to activation of JAK-STAT signaling pathway and influence gut function by upregulating the expression of specific target genes. This review considers the roles of cytokines and receptor-mediated activation of STATs on pathogen-induced changes in gut function. The focus on STAT4 and STAT6 is because of their requirement for the full development of Th1 and Th2 cytokine profiles. PMID:21327040

Exosomes and other extracellular vesicles in host–pathogen interactions

PubMed Central

Schorey, Jeffrey S; Cheng, Yong; Singh, Prachi P; Smith, Victoria L

2015-01-01

An effective immune response requires the engagement of host receptors by pathogen-derived molecules and the stimulation of an appropriate cellular response. Therefore, a crucial factor in our ability to control an infection is the accessibility of our immune cells to the foreign material. Exosomes—which are extracellular vesicles that function in intercellular communication—may play a key role in the dissemination of pathogen- as well as host-derived molecules during infection. In this review, we highlight the composition and function of exosomes and other extracellular vesicles produced during viral, parasitic, fungal and bacterial infections and describe how these vesicles could function to either promote or inhibit host immunity. PMID:25488940

Should I fight or should I grow now? The role of cytokinins in plant growth and immunity and in the growth–defence trade-off

PubMed Central

Albrecht, Tessa

2017-01-01

Background Perception and activation of plant immunity require a remarkable level of signalling plasticity and control. In Arabidopsis and other plant species, constitutive defence activation leads to resistance to a broad spectrum of biotrophic pathogens, but also frequently to stunted growth and reduced seed set. Plant hormones are important integrators of the physiological responses that influence the outcome of plant–pathogen interactions. Scope We review the mechanisms by which the plant hormone cytokinin regulates both plant growth and response to pathogens, and how cytokinins may connect these two processes, ultimately affecting the growth trade-offs observed in plant immunity. PMID:27864225

A moving view: subcellular trafficking processes in pattern recognition receptor-triggered plant immunity.

PubMed

Ben Khaled, Sara; Postma, Jelle; Robatzek, Silke

2015-01-01

A significant challenge for plants is to induce localized defense responses at sites of pathogen attack. Therefore, host subcellular trafficking processes enable accumulation and exchange of defense compounds, which contributes to the plant on-site defenses in response to pathogen perception. This review summarizes our current understanding of the transport processes that facilitate immunity, the significance of which is highlighted by pathogens reprogramming membrane trafficking through host cell translocated effectors. Prominent immune-related cargos of plant trafficking pathways are the pattern recognition receptors (PRRs), which must be present at the plasma membrane to sense microbes in the apoplast. We focus on the dynamic localization of the FLS2 receptor and discuss the pathways that regulate receptor transport within the cell and their link to FLS2-mediated immunity. One emerging theme is that ligand-induced late endocytic trafficking is conserved across different PRR protein families as well as across different plant species.

Functional Aspects of Fish Mucosal Lectins-Interaction with Non-Self.

PubMed

Brinchmann, Monica Fengsrud; Patel, Deepti Manjari; Pinto, Nevil; Iversen, Martin Haugmo

2018-05-09

Mucosal surfaces are of key importance in protecting animals against external threats including pathogens. In the mucosal surfaces, host molecules interact with non-self to prevent infection and disease. Interestingly, both inhibition and stimulation of uptake hinder infection. In this review, the current knowledgebase on teleost mucosal lectins’ ability to interact with non-self is summarised with a focus on agglutination, growth inhibition, opsonisation, cell adhesion, and direct killing activities. Further research on lectins is essential, both to understand the immune system of fishes, since they rely more on the innate immune system than mammals, and also to explore these molecules’ antibiotic and antiparasitic activities against veterinary and human pathogens.

Evolutionary Ecology of Multitrophic Interactions between Plants, Insect Herbivores and Entomopathogens.

PubMed

Shikano, Ikkei

2017-06-01

Plants play an important role in the interactions between insect herbivores and their pathogens. Since the seminal review by Cory and Hoover (2006) on plant-mediated effects on insect-pathogen interactions, considerable progress has been made in understanding the complexity of these tritrophic interactions. Increasing interest in the areas of nutritional and ecological immunology over the last decade have revealed that plant primary and secondary metabolites can influence the outcomes of insect-pathogen interactions by altering insect immune functioning and physical barriers to pathogen entry. Some insects use plant secondary chemicals and nutrients to prevent infections (prophylactic medication) and medicate to limit the severity of infections (therapeutic medication). Recent findings suggest that there may be selectable plant traits that enhance entomopathogen efficacy, suggesting that entomopathogens could potentially impose selection pressure on plant traits that improve both pathogen and plant fitness. Moreover, plants in nature are inhabited by diverse communities of microbes, in addition to entomopathogens, some of which can trigger immune responses in insect herbivores. Plants are also shared by numerous other herbivorous arthropods with different modes of feeding that can trigger different defensive responses in plants. Some insect symbionts and gut microbes can degrade ingested defensive phytochemicals and be orally secreted onto wounded plant tissue during herbivory to alter plant defenses. Since non-entomopathogenic microbes and other arthropods are likely to influence the outcomes of plant-insect-entomopathogen interactions, I discuss a need to consider these multitrophic interactions within the greater web of species interactions.

The role of effectors and host immunity in plant-necrotrophic fungal interactions.

PubMed

Wang, Xuli; Jiang, Nan; Liu, Jinling; Liu, Wende; Wang, Guo-Liang

2014-01-01

Fungal diseases pose constant threats to the global economy and food safety. As the largest group of plant fungal pathogens, necrotrophic fungi cause heavy crop losses worldwide. The molecular mechanisms of the interaction between necrotrophic fungi and plants are complex and involve sophisticated recognition and signaling networks. Here, we review recent findings on the roles of phytotoxin and proteinaceous effectors, pathogen-associated molecular patterns (PAMPs), and small RNAs from necrotrophic fungi. We also consider the functions of damage-associated molecular patterns (DAMPs), the receptor-like protein kinase BIK1, and epigenetic regulation in plant immunity to necrotrophic fungi.

Auxin crosstalk to plant immune networks: a plant-pathogen interaction perspective.

PubMed

Naseem, Muhammad; Srivastava, Mugdha; Tehseen, Muhammad; Ahmed, Nazeer

2015-01-01

The plant hormone auxin regulates a whole repertoire of plant growth and development. Many plant-associated microorganisms, by virtue of their auxin production capability, mediate phytostimulation effects on plants. Recent studies, however, demonstrate diverse mechanisms whereby plant pathogens manipulate auxin biosynthesis, signaling and transport pathways to promote host susceptibility. Auxin responses have been coupled to their antagonistic and synergistic interactions with salicylic acid and jasmonate mediated defenses, respectively. Here, we discuss that a better understanding of auxin crosstalk to plant immune networks would enable us to engineer crop plants with higher protection and low unintended yield losses.

Aspergillus flavus infection triggered immune responses and host-pathogen cross-talks in groundnut during in-vitro seed colonization

USDA-ARS?s Scientific Manuscript database

Aflatoxin contamination, caused by fungal pathogen Aspergillus flavus, is a major quality and health problem delimiting the trade and consumption of groundnut (Arachis hypogaea L.) worldwide. RNA-seq approach was deployed to understand the host-pathogen interaction by identifying differentially expr...

[Plant immune system: the basal immunity].

PubMed

Shamraĭ, S N

2014-01-01

Plants have an efficient system of innate immunity which is based on the effective detection of potentially harmful microorganisms and rapid induction of defense responses. The first level of plant immunity is the basal immunity which is induced by the conserved molecular structures of microbes such as bacterial flagellins or fungal chitin, or molecules that result from the interaction of plants with pathogens, for example oligosaccharides and peptides ("danger signals"). Plants recognize these inducers through receptors localized to the plasma membrane, represented mainly receptor-like protein kinases or receptor-like proteins. Activation of the receptor by a ligand triggers a complex network of signaling events which eventually cause an array of plant defense responses to prevent further spread of the pathogen.

Simple model of epidemics with pathogen mutation.

PubMed

Girvan, Michelle; Callaway, Duncan S; Newman, M E J; Strogatz, Steven H

2002-03-01

We study how the interplay between the memory immune response and pathogen mutation affects epidemic dynamics in two related models. The first explicitly models pathogen mutation and individual memory immune responses, with contacted individuals becoming infected only if they are exposed to strains that are significantly different from other strains in their memory repertoire. The second model is a reduction of the first to a system of difference equations. In this case, individuals spend a fixed amount of time in a generalized immune class. In both models, we observe four fundamentally different types of behavior, depending on parameters: (1) pathogen extinction due to lack of contact between individuals; (2) endemic infection; (3) periodic epidemic outbreaks; and (4) one or more outbreaks followed by extinction of the epidemic due to extremely low minima in the oscillations. We analyze both models to determine the location of each transition. Our main result is that pathogens in highly connected populations must mutate rapidly in order to remain viable.

Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

PubMed Central

Chattopadhyay, Saborni; Chen, Jui-Yi; Chen, Hui-Wen; Hu, Che-Ming Jack

2017-01-01

Synthetic nanoparticles play an increasingly significant role in vaccine design and development as many nanoparticle vaccines show improved safety and efficacy over conventional formulations. These nanoformulations are structurally similar to viruses, which are nanoscale pathogenic organisms that have served as a key selective pressure driving the evolution of our immune system. As a result, mechanisms behind the benefits of nanoparticle vaccines can often find analogue to the interaction dynamics between the immune system and viruses. This review covers the advances in vaccine nanotechnology with a perspective on the advantages of virus mimicry towards immune potentiation. It provides an overview to the different types of nanomaterials utilized for nanoparticle vaccine development, including functionalization strategies that bestow nanoparticles with virus-like features. As understanding of human immunity and vaccine mechanisms continue to evolve, recognizing the fundamental semblance between synthetic nanoparticles and viruses may offer an explanation for the superiority of nanoparticle vaccines over conventional vaccines and may spur new design rationales for future vaccine research. These nanoformulations are poised to provide solutions towards pressing and emerging human diseases. PMID:29071191

The function of small RNAs in plant biotic stress response.

PubMed

Huang, Juan; Yang, Meiling; Zhang, Xiaoming

2016-04-01

Small RNAs (sRNAs) play essential roles in plants upon biotic stress. Plants utilize RNA silencing machinery to facilitate pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity to defend against pathogen attack or to facilitate defense against insect herbivores. Pathogens, on the other hand, are also able to generate effectors and sRNAs to counter the host immune response. The arms race between plants and pathogens/insect herbivores has triggered the evolution of sRNAs, RNA silencing machinery and pathogen effectors. A great number of studies have been performed to investigate the roles of sRNAs in plant defense, bringing in the opportunity to utilize sRNAs in plant protection. Transgenic plants with pathogen-derived resistance ability or transgenerational defense have been generated, which show promising potential as solutions for pathogen/insect herbivore problems in the field. Here we summarize the recent progress on the function of sRNAs in response to biotic stress, mainly in plant-pathogen/insect herbivore interaction, and the application of sRNAs in disease and insect herbivore control. © 2016 Institute of Botany, Chinese Academy of Sciences.

Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection.

PubMed

Lovewell, Rustin R; Sassetti, Christopher M; VanderVen, Brian C

2016-02-01

The interplay between Mycobacterium tuberculosis lipid metabolism, the immune response and lipid homeostasis in the host creates a complex and dynamic pathogen-host interaction. Advances in imaging and metabolic analysis techniques indicate that M. tuberculosis preferentially associates with foamy cells and employs multiple physiological systems to utilize exogenously derived fatty-acids and cholesterol. Moreover, novel insights into specific host pathways that control lipid accumulation during infection, such as the PPARγ and LXR transcriptional regulators, have begun to reveal mechanisms by which host immunity alters the bacterial micro-environment. As bacterial lipid metabolism and host lipid regulatory pathways are both important, yet inherently complex, components of active tuberculosis, delineating the heterogeneity in lipid trafficking within disease states remains a major challenge for therapeutic design. Copyright © 2015. Published by Elsevier Ltd.

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, Leslie G.; Khare, Sangeeta; Lawhon, Sara D.

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhancedmore » approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic *sipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines.« less

Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: linking systems biology with vaccine development.

PubMed

Adams, L Garry; Khare, Sangeeta; Lawhon, Sara D; Rossetti, Carlos A; Lewin, Harris A; Lipton, Mary S; Turse, Joshua E; Wylie, Dennis C; Bai, Yu; Drake, Kenneth L

2011-09-22

The aim of research on infectious diseases is their prevention, and brucellosis and salmonellosis as such are classic examples of worldwide zoonoses for application of a systems biology approach for enhanced rational vaccine development. When used optimally, vaccines prevent disease manifestations, reduce transmission of disease, decrease the need for pharmaceutical intervention, and improve the health and welfare of animals, as well as indirectly protecting against zoonotic diseases of people. Advances in the last decade or so using comprehensive systems biology approaches linking genomics, proteomics, bioinformatics, and biotechnology with immunology, pathogenesis and vaccine formulation and delivery are expected to enable enhanced approaches to vaccine development. The goal of this paper is to evaluate the role of computational systems biology analysis of host:pathogen interactions (the interactome) as a tool for enhanced rational design of vaccines. Systems biology is bringing a new, more robust approach to veterinary vaccine design based upon a deeper understanding of the host-pathogen interactions and its impact on the host's molecular network of the immune system. A computational systems biology method was utilized to create interactome models of the host responses to Brucella melitensis (BMEL), Mycobacterium avium paratuberculosis (MAP), Salmonella enterica Typhimurium (STM), and a Salmonella mutant (isogenic ΔsipA, sopABDE2) and linked to the basis for rational development of vaccines for brucellosis and salmonellosis as reviewed by Adams et al. and Ficht et al. [1,2]. A bovine ligated ileal loop biological model was established to capture the host gene expression response at multiple time points post infection. New methods based on Dynamic Bayesian Network (DBN) machine learning were employed to conduct a comparative pathogenicity analysis of 219 signaling and metabolic pathways and 1620 gene ontology (GO) categories that defined the host's biosignatures to each infectious condition. Through this DBN computational approach, the method identified significantly perturbed pathways and GO category groups of genes that define the pathogenicity signatures of the infectious agent. Our preliminary results provide deeper understanding of the overall complexity of host innate immune response as well as the identification of host gene perturbations that defines a unique host temporal biosignature response to each pathogen. The application of advanced computational methods for developing interactome models based on DBNs has proven to be instrumental in elucidating novel host responses and improved functional biological insight into the host defensive mechanisms. Evaluating the unique differences in pathway and GO perturbations across pathogen conditions allowed the identification of plausible host-pathogen interaction mechanisms. Accordingly, a systems biology approach to study molecular pathway gene expression profiles of host cellular responses to microbial pathogens holds great promise as a methodology to identify, model and predict the overall dynamics of the host-pathogen interactome. Thus, we propose that such an approach has immediate application to the rational design of brucellosis and salmonellosis vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

Approaches to understanding the impact of life-history features on plant-pathogen co-evolutionary dynamics

Treesearch

Jeremy J. Burdon; Peter H. Thrall; Adnane Nemri

2012-01-01

Natural plant-pathogen associations are complex interactions in which the interplay of environment, host, and pathogen factors results in spatially heterogeneous ecological and epidemiological dynamics. The evolutionary patterns that result from the interaction of these factors are still relatively poorly understood. Recently, integration of the appropriate spatial and...

Cholera in the 21st century.

PubMed

Charles, Richelle C; Ryan, Edward T

2011-10-01

This review will focus on recent advances in our understanding of biologic and environmental factors that shape current cholera outbreaks, advances in our understanding of host-pathogen interactions during cholera, and recent evolution of current treatment and cholera prevention strategies. New research studies have improved our understanding of a number of dynamic factors that shape the ecology of Vibrio cholerae and influence its transmission, including the role of lytic bacteriophage, biofilm formation, a hyperinfectious state of human-passaged V. cholerae, and the impact of severe weather events. Provision of safe water and improved sanitation continue to be the mainstays of preventing cholera transmission; however, the role of cholera vaccination as a control measure in both endemic and epidemic settings is evolving. Recent advances in our understanding of long-lived protective immunity after natural infection may aid in the global efforts to control cholera. Improved understanding of factors associated with protective immunity and dynamic factors associated with cholera outbreaks may lead to improved control and prevention strategies for cholera.

Organization of an optimal adaptive immune system

NASA Astrophysics Data System (ADS)

Walczak, Aleksandra; Mayer, Andreas; Balasubramanian, Vijay; Mora, Thierry

The repertoire of lymphocyte receptors in the adaptive immune system protects organisms from a diverse set of pathogens. A well-adapted repertoire should be tuned to the pathogenic environment to reduce the cost of infections. I will discuss a general framework for predicting the optimal repertoire that minimizes the cost of infections contracted from a given distribution of pathogens. The theory predicts that the immune system will have more receptors for rare antigens than expected from the frequency of encounters and individuals exposed to the same infections will have sparse repertoires that are largely different, but nevertheless exploit cross-reactivity to provide the same coverage of antigens. I will show that the optimal repertoires can be reached by dynamics that describes the competitive binding of antigens by receptors, and selective amplification of stimulated receptors.

Local and Long-Distance Calling: Conversations between the Gut Microbiota and Intra- and Extra-Gastrointestinal Tract Infections.

PubMed

Denny, Joshua E; Powell, Whitney L; Schmidt, Nathan W

2016-01-01

Preservation of health from infectious diseases depends upon both mucosal and systemic immunity via the collaborative effort of innate and adaptive immune responses. The proficiency of host immunity stems from robust defense mechanisms--physical barriers and specialized immune cells--and a failure of these mechanisms leads to pathology. Intriguingly, immunocompetence to pathogens can be shaped by the gut microbiome as recent publications highlight a dynamic interplay between the gut microbiome and host susceptibility to infection. Modulation of host immunity to enteric pathogens has long been studied where gut bacteria shape multiple facts of both innate and adaptive immunity. Conversely, the impact of gut commensals on host immunity to extra-gastrointestinal (GI) tract infections has only recently been recognized. In this context, the gut microbiome can augment host immunity to extra-GI tract bacterial, viral, and parasitic pathogens. This review explores the research that affords insight into the role of the gut microbiome in various infectious diseases, with a particular emphasis on extra-GI tract infections. A better understanding of the link between the gut microbiome and infectious disease will be critical for improving global health in the years ahead.

Recent progress in elucidating the structure, function and evolution of disease resistance genes in plants.

PubMed

Liu, Jinling; Liu, Xionglun; Dai, Liangying; Wang, Guoliang

2007-09-01

Plants employ multifaceted mechanisms to fight with numerous pathogens in nature. Resistance (R) genes are the most effective weapons against pathogen invasion since they can specifically recognize the corresponding pathogen effectors or associated protein(s) to activate plant immune responses at the site of infection. Up to date, over 70 R genes have been isolated from various plant species. Most R proteins contain conserved motifs such as nucleotide-binding site (NBS), leucine-rich repeat (LRR), Toll-interleukin-1 receptor domain (TIR, homologous to cytoplasmic domains of the Drosophila Toll protein and the mammalian interleukin-1 receptor), coiled-coil (CC) or leucine zipper (LZ) structure and protein kinase domain (PK). Recent results indicate that these domains play significant roles in R protein interactions with effector proteins from pathogens and in activating signal transduction pathways involved in innate immunity. This review highlights an overview of the recent progress in elucidating the structure, function and evolution of the isolated R genes in different plant-pathogen interaction systems.

Host-Brucella interactions and the Brucella genome as tools for subunit antigen discovery and immunization against brucellosis

PubMed Central

Gomez, Gabriel; Adams, Leslie G.; Rice-Ficht, Allison; Ficht, Thomas A.

2013-01-01

Vaccination is the most important approach to counteract infectious diseases. Thus, the development of new and improved vaccines for existing, emerging, and re-emerging diseases is an area of great interest to the scientific community and general public. Traditional approaches to subunit antigen discovery and vaccine development lack consideration for the critical aspects of public safety and activation of relevant protective host immunity. The availability of genomic sequences for pathogenic Brucella spp. and their hosts have led to development of systems-wide analytical tools that have provided a better understanding of host and pathogen physiology while also beginning to unravel the intricacies at the host-pathogen interface. Advances in pathogen biology, host immunology, and host-agent interactions have the potential to serve as a platform for the design and implementation of better-targeted antigen discovery approaches. With emphasis on Brucella spp., we probe the biological aspects of host and pathogen that merit consideration in the targeted design of subunit antigen discovery and vaccine development. PMID:23720712

Evolutionary dynamics of Hepatitis C virus in a chronic HIV co-infected patient and its correlation with the immune status.

PubMed

Culasso, Andrés Carlos Alberto; Monzani, María Cecilia; Baré, Patricia; Campos, Rodolfo Hector

2018-05-04

The HCV evolutionary dynamics play a key role in the infection onset, maintenance of chronicity, pathogenicity, and drug resistance variants fixation, and are thought to be one of the main caveats in the development of an effective vaccine. Previous studies in HCV/HIV co-infected patients suggest that a decline in the immune status is related with increases in the HCV intra-host genetic diversity. However, these findings are based on single point sequence diversity measures or coalescence analyses in several virus-host interactions. In this work, we describe the molecular evolution of HCV-E2 region in a single HIV-co-infected patient with two clearly defined immune conditions. The phylogenetic analysis of the HCV-1a sequences from the studied patient showed that he was co-infected with three different viral lineages. These lineages were not evenly detected throughout time. The sequence diversity and coalescence analyses of these lineages suggested the action of different evolutionary patterns in different immune conditions: a slow rate, drift-like process in an immunocompromised condition (low levels of CD4+ T lymphocytes); and a fast rate, variant-switch process in an immunocompetent condition (high levels of CD4+ T lymphocytes). Copyright © 2017. Published by Elsevier B.V.

A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host–Pathogen Interaction Networks

PubMed Central

Wu, Chia-Chou; Chen, Bor-Sen

2016-01-01

Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host–pathogen dynamic interaction networks. The consideration of host–pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host–pathogen molecular interaction networks, and consequent inferences of the host–pathogen relationship could be translated into biomedical applications. PMID:26881892

A Systems Biology Approach to the Coordination of Defensive and Offensive Molecular Mechanisms in the Innate and Adaptive Host-Pathogen Interaction Networks.

PubMed

Wu, Chia-Chou; Chen, Bor-Sen

2016-01-01

Infected zebrafish coordinates defensive and offensive molecular mechanisms in response to Candida albicans infections, and invasive C. albicans coordinates corresponding molecular mechanisms to interact with the host. However, knowledge of the ensuing infection-activated signaling networks in both host and pathogen and their interspecific crosstalk during the innate and adaptive phases of the infection processes remains incomplete. In the present study, dynamic network modeling, protein interaction databases, and dual transcriptome data from zebrafish and C. albicans during infection were used to infer infection-activated host-pathogen dynamic interaction networks. The consideration of host-pathogen dynamic interaction systems as innate and adaptive loops and subsequent comparisons of inferred innate and adaptive networks indicated previously unrecognized crosstalk between known pathways and suggested roles of immunological memory in the coordination of host defensive and offensive molecular mechanisms to achieve specific and powerful defense against pathogens. Moreover, pathogens enhance intraspecific crosstalk and abrogate host apoptosis to accommodate enhanced host defense mechanisms during the adaptive phase. Accordingly, links between physiological phenomena and changes in the coordination of defensive and offensive molecular mechanisms highlight the importance of host-pathogen molecular interaction networks, and consequent inferences of the host-pathogen relationship could be translated into biomedical applications.

NFP, a LysM protein controlling Nod factor perception, also intervenes in Medicago truncatula resistance to pathogens.

PubMed

Rey, Thomas; Nars, Amaury; Bonhomme, Maxime; Bottin, Arnaud; Huguet, Stéphanie; Balzergue, Sandrine; Jardinaud, Marie-Françoise; Bono, Jean-Jacques; Cullimore, Julie; Dumas, Bernard; Gough, Clare; Jacquet, Christophe

2013-05-01

Plant LysM proteins control the perception of microbial-derived N-acetylglucosamine compounds for the establishment of symbiosis or activation of plant immunity. This raises questions about how plants, and notably legumes, can differentiate friends and foes using similar molecular actors and whether any receptors can intervene in both symbiosis and resistance. To study this question, nfp and lyk3 LysM-receptor like kinase mutants of Medicago truncatula that are affected in the early steps of nodulation, were analysed following inoculation with Aphanomyces euteiches, a root oomycete. The role of NFP in this interaction was further analysed by overexpression of NFP and by transcriptome analyses. nfp, but not lyk3, mutants were significantly more susceptible than wildtype plants to A. euteiches, whereas NFP overexpression increased resistance. Transcriptome analyses on A. euteiches inoculation showed that mutation in the NFP gene led to significant changes in the expression of c. 500 genes, notably involved in cell dynamic processes previously associated with resistance to pathogen penetration. nfp mutants also showed an increased susceptibility to the fungus Colletotrichum trifolii. These results demonstrate that NFP intervenes in M. truncatula immunity, suggesting an unsuspected role for NFP in the perception of pathogenic signals. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Interaction effects of different drivers of wild bee decline and their influence on host-pathogen dynamics.

PubMed

Meeus, Ivan; Pisman, Matti; Smagghe, Guy; Piot, Niels

2018-04-01

Wild bee decline is a multi-factorial problem, yet it is crucial to understand the impact of a single driver. Hereto the interaction effects of wild bee decline with multiple natural and anthropogenic stressors need to be clear. This is also true for the driver 'pathogens', as stressor induced disturbances of natural host-pathogen dynamics can unbalance settled virulence equilibria. Invasive species, bee domestication, habitat loss, climate changes and insecticides are recognized drivers of wild bee decline, but all influence host-pathogen dynamics as well. Many wild bee pathogens have multiple hosts, which relaxes the host-density limitation of virulence evolution. In conclusion, disturbances of bee-pathogen dynamics can be compared to a game of Russian roulette. Copyright © 2018. Published by Elsevier Inc.

Ca2+/Calmodulin-Dependent AtSR1/CAMTA3 Plays Critical Roles in Balancing Plant Growth and Immunity.

PubMed

Yuan, Peiguo; Du, Liqun; Poovaiah, B W

2018-06-14

During plant-pathogen interactions, plants have to relocate their resources including energy to defend invading organisms; as a result, plant growth and development are usually reduced. Arabidopsis signal responsive1 (AtSR1) has been documented as a negative regulator of plant immune responses and could serve as a positive regulator of plant growth and development. However, the mechanism by which AtSR1 balances plant growth and immunity is poorly understood. Here, we performed a global gene expression profiling using Affymetrix microarrays to study how AtSR1 regulates defense- and growth-related genes in plants with and without bacterial pathogen infection. Results revealed that AtSR1 negatively regulates most of the immune-related genes involved in molecular pattern-triggered immunity (PTI), effector-triggered immunity (ETI), and in salicylic acid (SA)- and jasmonate (JA)-mediated signaling pathways. AtSR1 may rigidly regulate several steps of the SA-mediated pathway, from the activation of SA synthesis to the perception of SA signal. Furthermore, AtSR1 may also regulate plant growth through its involvement in regulating auxin- and BRs-related pathways. Although microarray data revealed that expression levels of defense-related genes induced by pathogens are higher in wild-type (WT) plants than that in atsr1 mutant plants, WT plants are more susceptible to the infection of virulent pathogen as compared to atsr1 mutant plants. These observations indicate that the AtSR1 functions in suppressing the expression of genes induced by pathogen attack and contributes to the rapid establishment of resistance in WT background. Results of electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR assays suggest that AtSR1 acts as transcription factor in balancing plant growth and immunity, through interaction with the “CGCG” containing CG-box in the promotors of its target genes.

Enemy at the gates: traffic at the plant cell pathogen interface.

PubMed

Hoefle, Caroline; Hückelhoven, Ralph

2008-12-01

The plant apoplast constitutes a space for early recognition of potentially harmful non-self. Basal pathogen recognition operates via dynamic sensing of conserved microbial patterns by pattern recognition receptors or of elicitor-active molecules released from plant cell walls during infection. Recognition elicits defence reactions depending on cellular export via SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex-mediated vesicle fusion or plasma membrane transporter activity. Lipid rafts appear also involved in focusing immunity-associated proteins to the site of pathogen contact. Simultaneously, pathogen effectors target recognition, apoplastic host proteins and transport for cell wall-associated defence. This microreview highlights most recent reports on the arms race for plant disease and immunity at the cell surface.

The Arabidopsis Cysteine-Rich Receptor-Like Kinase CRK36 Regulates Immunity through Interaction with the Cytoplasmic Kinase BIK1

PubMed Central

Lee, Dong Sook; Kim, Young Cheon; Kwon, Sun Jae; Ryu, Choong-Min; Park, Ohkmae K.

2017-01-01

Receptor-like kinases are important signaling components that regulate a variety of cellular processes. In this study, an Arabidopsis cDNA microarray analysis led to the identification of the cysteine-rich receptor-like kinase CRK36 responsive to the necrotrophic fungal pathogen, Alternaria brassicicola. To determine the function of CRK36 in plant immunity, T-DNA-insertion knockdown (crk36) and overexpressing (CRK36OE) plants were prepared. CRK36OE plants exhibited increased hypersensitive cell death and ROS burst in response to avirulent pathogens. Treatment with a typical pathogen-associated molecular pattern, flg22, markedly induced pattern-triggered immune responses, notably stomatal defense, in CRK36OE plants. The immune responses were weakened in crk36 plants. Protein-protein interaction assays revealed the in vivo association of CRK36, FLS2, and BIK1. CRK36 enhanced flg22-triggered BIK1 phosphorylation, which showed defects with Cys mutations in the DUF26 motifs of CRK36. Disruption of BIK1 and RbohD/RbohF genes further impaired CRK36-mediated stomatal defense. We propose that CRK36, together with BIK1 and NADPH oxidases, may form a positive activation loop that enhances ROS burst and leads to the promotion of stomatal immunity. PMID:29163585

Bacterial Outer Membrane Vesicles Induce Plant Immune Responses.

PubMed

Bahar, Ofir; Mordukhovich, Gideon; Luu, Dee Dee; Schwessinger, Benjamin; Daudi, Arsalan; Jehle, Anna Kristina; Felix, Georg; Ronald, Pamela C

2016-05-01

Gram-negative bacteria continuously pinch off portions of their outer membrane, releasing membrane vesicles. These outer membrane vesicles (OMVs) are involved in multiple processes including cell-to-cell communication, biofilm formation, stress tolerance, horizontal gene transfer, and virulence. OMVs are also known modulators of the mammalian immune response. Despite the well-documented role of OMVs in mammalian-bacterial communication, their interaction with plants is not well studied. To examine whether OMVs of plant pathogens modulate the plant immune response, we purified OMVs from four different plant pathogens and used them to treat Arabidopsis thaliana. OMVs rapidly induced a reactive oxygen species burst, medium alkalinization, and defense gene expression in A. thaliana leaf discs, cell cultures, and seedlings, respectively. Western blot analysis revealed that EF-Tu is present in OMVs and that it serves as an elicitor of the plant immune response in this form. Our results further show that the immune coreceptors BAK1 and SOBIR1 mediate OMV perception and response. Taken together, our results demonstrate that plants can detect and respond to OMV-associated molecules by activation of their immune system, revealing a new facet of plant-bacterial interactions.

Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion.

PubMed

Hopke, Alex; Brown, Alistair J P; Hall, Rebecca A; Wheeler, Robert T

2018-04-01

Deadly infections from opportunistic fungi have risen in frequency, largely because of the at-risk immunocompromised population created by advances in modern medicine and the HIV/AIDS pandemic. This review focuses on dynamics of the fungal polysaccharide cell wall, which plays an outsized role in fungal pathogenesis and therapy because it acts as both an environmental barrier and as the major interface with the host immune system. Human fungal pathogens use architectural strategies to mask epitopes from the host and prevent immune surveillance, and recent work elucidates how biotic and abiotic stresses present during infection can either block or enhance masking. The signaling components implicated in regulating fungal immune recognition can teach us how cell wall dynamics are controlled, and represent potential targets for interventions designed to boost or dampen immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Age, pathogen exposure, but not maternal care shape offspring immunity in an insect with facultative family life.

PubMed

Vogelweith, Fanny; Körner, Maximilian; Foitzik, Susanne; Meunier, Joël

2017-03-07

To optimize their resistance against pathogen infection, individuals are expected to find the right balance between investing into the immune system and other life history traits. In vertebrates, several factors were shown to critically affect the direction of this balance, such as the developmental stage of an individual, its current risk of infection and/or its access to external help such as parental care. However, the independent and/or interactive effects of these factors on immunity remain poorly studied in insects. Here, we manipulated maternal presence and pathogen exposure in families of the European earwig Forficula auricularia to measure whether and how the survival rate and investment into two key immune parameters changed during offspring development. The pathogen was the entomopathogenic fungus Metarhizium brunneum and the immune parameters were hemocyte concentration and phenol/pro-phenoloxidase enzyme activity (total-PO). Our results surprisingly showed that maternal presence had no effect on offspring immunity, but reduced offspring survival. Pathogen exposure also lowered the survival of offspring during their early development. The concentration of hemocytes and the total-PO activity increased during development, to be eventually higher in adult females compared to adult males. Finally, pathogen exposure overall increased the concentration of hemocytes-but not the total-PO activity-in adults, while it had no effect on these measures in offspring. Our results show that, independent of their infection risk and developmental stage, maternal presence does not shape immune defense in young earwigs. This reveals that pathogen pressure is not a universal evolutionary driver of the emergence and maintenance of post-hatching maternal care in insects.

Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

PubMed

Yang, Huiying; Ke, Yuehua; Wang, Jian; Tan, Yafang; Myeni, Sebenzile K; Li, Dong; Shi, Qinghai; Yan, Yanfeng; Chen, Hui; Guo, Zhaobiao; Yuan, Yanzhi; Yang, Xiaoming; Yang, Ruifu; Du, Zongmin

2011-11-01

A Yersinia pestis-human protein interaction network is reported here to improve our understanding of its pathogenesis. Up to 204 interactions between 66 Y. pestis bait proteins and 109 human proteins were identified by yeast two-hybrid assay and then combined with 23 previously published interactions to construct a protein-protein interaction network. Topological analysis of the interaction network revealed that human proteins targeted by Y. pestis were significantly enriched in the proteins that are central in the human protein-protein interaction network. Analysis of this network showed that signaling pathways important for host immune responses were preferentially targeted by Y. pestis, including the pathways involved in focal adhesion, regulation of cytoskeleton, leukocyte transendoepithelial migration, and Toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) signaling. Cellular pathways targeted by Y. pestis are highly relevant to its pathogenesis. Interactions with host proteins involved in focal adhesion and cytoskeketon regulation pathways could account for resistance of Y. pestis to phagocytosis. Interference with TLR and MAPK signaling pathways by Y. pestis reflects common characteristics of pathogen-host interaction that bacterial pathogens have evolved to evade host innate immune response by interacting with proteins in those signaling pathways. Interestingly, a large portion of human proteins interacting with Y. pestis (16/109) also interacted with viral proteins (Epstein-Barr virus [EBV] and hepatitis C virus [HCV]), suggesting that viral and bacterial pathogens attack common cellular functions to facilitate infections. In addition, we identified vasodilator-stimulated phosphoprotein (VASP) as a novel interaction partner of YpkA and showed that YpkA could inhibit in vitro actin assembly mediated by VASP.

The role of effectors and host immunity in plant–necrotrophic fungal interactions

PubMed Central

Wang, Xuli; Jiang, Nan; Liu, Jinling; Liu, Wende; Wang, Guo-Liang

2014-01-01

Fungal diseases pose constant threats to the global economy and food safety. As the largest group of plant fungal pathogens, necrotrophic fungi cause heavy crop losses worldwide. The molecular mechanisms of the interaction between necrotrophic fungi and plants are complex and involve sophisticated recognition and signaling networks. Here, we review recent findings on the roles of phytotoxin and proteinaceous effectors, pathogen-associated molecular patterns (PAMPs), and small RNAs from necrotrophic fungi. We also consider the functions of damage-associated molecular patterns (DAMPs), the receptor-like protein kinase BIK1, and epigenetic regulation in plant immunity to necrotrophic fungi. PMID:25513773

ENHANCED DISEASE RESISTANCE4 Associates with CLATHRIN HEAVY CHAIN2 and Modulates Plant Immunity by Regulating Relocation of EDR1 in Arabidopsis

PubMed Central

Wu, Guangheng; Liu, Simu; Zhao, Yaofei; Wang, Wei; Kong, Zhaosheng; Tang, Dingzhong

2015-01-01

Obligate biotrophs, such as the powdery mildew pathogens, deliver effectors to the host cell and obtain nutrients from the infection site. The interface between the plant host and the biotrophic pathogen thus represents a major battleground for plant-pathogen interactions. Increasing evidence shows that cellular trafficking plays an important role in plant immunity. Here, we report that Arabidopsis thaliana ENHANCED DISEASE RESISTANCE4 (EDR4) plays a negative role in resistance to powdery mildew and that the enhanced disease resistance in edr4 mutants requires salicylic acid signaling. EDR4 mainly localizes to the plasma membrane and endosomal compartments. Genetic analyses show that EDR4 and EDR1 function in the same genetic pathway. EDR1 and EDR4 accumulate at the penetration site of powdery mildew infection, and EDR4 physically interacts with EDR1, recruiting EDR1 to the fungal penetration site. In addition, EDR4 interacts with CLATHRIN HEAVY CHAIN2 (CHC2), and edr4 mutants show reduced endocytosis rates. Taken together, our data indicate that EDR4 associates with CHC2 and modulates plant immunity by regulating the relocation of EDR1 in Arabidopsis. PMID:25747881

Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer’s Disease

PubMed Central

Harris, Steven A.; Harris, Elizabeth A.

2015-01-01

Abstract This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer’s disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-β (Aβ) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of Aβ damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials. PMID:26401998

Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens

PubMed Central

Cabinian, Allison; Sinsimer, Daniel; Tang, May; Jang, Youngsoon; Choi, Bongkum; Laouar, Yasmina; Laouar, Amale

2018-01-01

Background Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field. Aim We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is. Methods Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFPtg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium. Results SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC)TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death. Conclusions SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut. PMID:28341747

Critical disease windows shaped by stress exposure alter allocation trade-offs between development and immunity.

PubMed

Kirschman, Lucas J; Crespi, Erica J; Warne, Robin W

2018-01-01

Ubiquitous environmental stressors are often thought to alter animal susceptibility to pathogens and contribute to disease emergence. However, duration of exposure to a stressor is likely critical, because while chronic stress is often immunosuppressive, acute stress can temporarily enhance immune function. Furthermore, host susceptibility to stress and disease often varies with ontogeny; increasing during critical developmental windows. How the duration and timing of exposure to stressors interact to shape critical windows and influence disease processes is not well tested. We used ranavirus and larval amphibians as a model system to investigate how physiological stress and pathogenic infection shape development and disease dynamics in vertebrates. Based on a resource allocation model, we designed experiments to test how exposure to stressors may induce resource trade-offs that shape critical windows and disease processes because the neuroendocrine stress axis coordinates developmental remodelling, immune function and energy allocation in larval amphibians. We used wood frog larvae (Lithobates sylvaticus) to investigate how chronic and acute exposure to corticosterone, the dominant amphibian glucocorticoid hormone, mediates development and immune function via splenocyte immunohistochemistry analysis in association with ranavirus infection. Corticosterone treatments affected immune function, as both chronic and acute exposure suppressed splenocyte proliferation, although viral replication rate increased only in the chronic corticosterone treatment. Time to metamorphosis and survival depended on both corticosterone treatment and infection status. In the control and chronic corticosterone treatments, ranavirus infection decreased survival and delayed metamorphosis, although chronic corticosterone exposure accelerated rate of metamorphosis in uninfected larvae. Acute corticosterone exposure accelerated metamorphosis increased survival in infected larvae. Interactions between stress exposure (via glucocorticoid actions) and infection impose resource trade-offs that shape optimal allocation between development and somatic function. As a result, critical disease windows are likely shaped by stress exposure because any conditions that induce changes in differentiation rates will alter the duration and susceptibility of organisms to stressors or disease. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Imaging early pathogenesis of bubonic plague: are neutrophils commandeered for lymphatic transport of bacteria?

PubMed

Bland, David M; Anderson, Deborah M

2013-11-05

Vector-borne infections begin in the dermis when a pathogen is introduced by an arthropod during a blood meal. Several barriers separate an invading pathogen from its replicative niche, including phagocytic cells in the dermis that activate immunity by engulfing would-be pathogens and migrating to the lymph node. In addition, neutrophils circulating in the blood are rapidly recruited when the dermal barriers are penetrated. For flea-borne disease, no insect-encoded immune-suppressive molecules have yet been described that might influence the establishment of infection, leaving the bacteria on their own to defend against the mammalian immune system. Shortly after a flea transmits Yersinia pestis to a mammalian host, the bacteria are transported to the lymph node, where they grow logarithmically and later spread systemically. Even a single cell of Y. pestis can initiate a lethal case of plague. In their article, J. G. Shannon et al. [mBio 4(5):e00170-13, 2013, doi:10.1128/mBio.00170-13] used intravital microscopy to visualize trafficking of Y. pestis in transgenic mice in vivo, which allowed them to examine interactions between bacteria and specific immune cells. Bacteria appeared to preferentially interact with neutrophils but had no detectable interactions with dendritic cells. These findings suggest that Y. pestis infection of neutrophils not only prevents their activation but may even result in their return to circulation and migration to distal sites.

Host genetics affect microbial ecosystems via host immunity.

PubMed

El Kafsi, Hela; Gorochov, Guy; Larsen, Martin

2016-10-01

Genetic evolution of multicellular organisms has occurred in response to environmental challenges, including competition for nutrients, climate change, physical and chemical stressors, and pathogens. However, fitness of an organism is dependent not only on defense efficacy, but also on the ability to take advantage of symbiotic organisms. Indeed, microbes not only encompass pathogenicity, but also enable efficient nutrient uptake from diets nondegradable by the host itself. Moreover, microbes play important roles in the development of host immunity. Here we review associations between specific host genes and variance in microbiota composition and compare with interactions between microbes and host immunity. Recent genome-wide association studies reveal that symbiosis between host and microbiota is the exquisite result of genetic coevolution. Moreover, a subset of microbes from human and mouse microbiota have been identified to interact with humoral and cellular immunity. Interestingly, microbes associated with both host genetics and host immunity are taxonomically related. Most involved are Bifidobacterium, Lactobacillus, and Akkermansia, which are dually associated with both host immunity and host genetics. We conclude that future therapeutics targeting microbiota in the context of chronic inflammatory diseases need to consider both immune and genetic host features associated with microbiota homeostasis.

Cooperative microbial tolerance behaviors in host-microbiota mutualism

PubMed Central

Ayres, Janelle S.

2016-01-01

Animal defense strategies against microbes are most often thought of as a function of the immune system, the primary function of which is to sense and kill microbes through the execution of resistance mechanisms. However, this antagonistic view creates complications for our understanding of beneficial host-microbe interactions. Pathogenic microbes are described as employing a few common behaviors that promote their fitness at the expense of host health and fitness. Here, a complementary framework is proposed to suggest that in addition to pathogens, beneficial microbes have evolved behaviors to manipulate host processes in order to promote their own fitness and do so through the promotion of host health and fitness. In this Perspective, I explore the idea that patterns or behaviors traditionally ascribed to pathogenic microbes are also employed by beneficial microbes to promote host tolerance defense strategies. Such strategies would promote host health without having a negative impact on microbial fitness and would thereby yield cooperative evolutionary dynamics that are likely required to drive mutualistic co-evolution of hosts and microbes. PMID:27259146

The Arginine Decarboxylase Pathways of Host and Pathogen Interact to Impact Inflammatory Pathways in the Lung

PubMed Central

Dalluge, Joseph J.; Welchlin, Cole W.; Hughes, John; Han, Wei; Blackwell, Timothy S.; Laguna, Theresa A.; Williams, Bryan J.

2014-01-01

The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic. PMID:25350753

The arginine decarboxylase pathways of host and pathogen interact to impact inflammatory pathways in the lung.

PubMed

Paulson, Nick B; Gilbertsen, Adam J; Dalluge, Joseph J; Welchlin, Cole W; Hughes, John; Han, Wei; Blackwell, Timothy S; Laguna, Theresa A; Williams, Bryan J

2014-01-01

The arginine decarboxylase pathway, which converts arginine to agmatine, is present in both humans and most bacterial pathogens. In humans agmatine is a neurotransmitter with affinities towards α2-adrenoreceptors, serotonin receptors, and may inhibit nitric oxide synthase. In bacteria agmatine serves as a precursor to polyamine synthesis and was recently shown to enhance biofilm development in some strains of the respiratory pathogen Pseudomonas aeruginosa. We determined agmatine is at the center of a competing metabolism in the human lung during airways infections and is influenced by the metabolic phenotypes of the infecting pathogens. Ultra performance liquid chromatography with mass spectrometry detection was used to measure agmatine in human sputum samples from patients with cystic fibrosis, spent supernatant from clinical sputum isolates, and from bronchoalvelolar lavage fluid from mice infected with P. aeruginosa agmatine mutants. Agmatine in human sputum peaks during illness, decreased with treatment and is positively correlated with inflammatory cytokines. Analysis of the agmatine metabolic phenotype in clinical sputum isolates revealed most deplete agmatine when grown in its presence; however a minority appeared to generate large amounts of agmatine presumably driving sputum agmatine to high levels. Agmatine exposure to inflammatory cells and in mice demonstrated its role as a direct immune activator with effects on TNF-α production, likely through NF-κB activation. P. aeruginosa mutants for agmatine detection and metabolism were constructed and show the real-time evolution of host-derived agmatine in the airways during acute lung infection. These experiments also demonstrated pathogen agmatine production can upregulate the inflammatory response. As some clinical isolates have adapted to hypersecrete agmatine, these combined data would suggest agmatine is a novel target for immune modulation in the host-pathogen dynamic.

Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

PubMed Central

Mina, Michael J.; McCullers, Jonathan A.; Klugman, Keith P.

2014-01-01

ABSTRACT Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. PMID:24549845

The other white-nose syndrome transcriptome: Tolerant and susceptible hosts respond differently to the pathogen Pseudogymnoascus destructans.

PubMed

Davy, Christina M; Donaldson, Michael E; Willis, Craig K R; Saville, Barry J; McGuire, Liam P; Mayberry, Heather; Wilcox, Alana; Wibbelt, Gudrun; Misra, Vikram; Bollinger, Trent; Kyle, Christopher J

2017-09-01

Mitigation of emerging infectious diseases that threaten global biodiversity requires an understanding of critical host and pathogen responses to infection. For multihost pathogens where pathogen virulence or host susceptibility is variable, host-pathogen interactions in tolerant species may identify potential avenues for adaptive evolution in recently exposed, susceptible hosts. For example, the fungus Pseudogymnoascus destructans causes white-nose syndrome (WNS) in hibernating bats and is responsible for catastrophic declines in some species in North America, where it was recently introduced. Bats in Europe and Asia, where the pathogen is endemic, are only mildly affected. Different environmental conditions among Nearctic and Palearctic hibernacula have been proposed as an explanation for variable disease outcomes, but this hypothesis has not been experimentally tested. We report the first controlled, experimental investigation of response to P. destructans in a tolerant, European species of bat (the greater mouse-eared bat, Myotis myotis ). We compared body condition, disease outcomes and gene expression in control (sham-exposed) and exposed M. myotis that hibernated under controlled environmental conditions following treatment. Tolerant M. myotis experienced extremely limited fungal growth and did not exhibit symptoms of WNS. However, we detected no differential expression of genes associated with immune response in exposed bats, indicating that immune response does not drive tolerance of P. destructans in late hibernation. Variable responses to P. destructans among bat species cannot be attributed solely to environmental or ecological factors. Instead, our results implicate coevolution with the pathogen, and highlight the dynamic nature of the "white-nose syndrome transcriptome." Interspecific variation in response to exposure by the host (and possibly pathogen) emphasizes the importance of context in studies of the bat-WNS system, and robust characterization of genetic responses to exposure in various hosts and the pathogen should precede any attempts to use particular bat species as generalizable "model hosts."

Antagonism between salicylic and abscisic acid reflects early host-pathogen conflict and moulds plant defence responses.

PubMed

de Torres Zabala, Marta; Bennett, Mark H; Truman, William H; Grant, Murray R

2009-08-01

The importance of phytohormone balance is increasingly recognized as central to the outcome of plant-pathogen interactions. Recently it has been demonstrated that abscisic acid signalling pathways are utilized by the bacterial phytopathogen Pseudomonas syringae to promote pathogenesis. In this study, we examined the dynamics, inter-relationship and impact of three key acidic phytohormones, salicylic acid, abscisic acid and jasmonic acid, and the bacterial virulence factor, coronatine, during progression of P. syringae infection of Arabidopsis thaliana. We show that levels of SA and ABA, but not JA, appear to play important early roles in determining the outcome of the infection process. SA is required in order to mount a full innate immune responses, while bacterial effectors act rapidly to activate ABA biosynthesis. ABA suppresses inducible innate immune responses by down-regulating SA biosynthesis and SA-mediated defences. Mutant analyses indicated that endogenous ABA levels represent an important reservoir that is necessary for effector suppression of plant-inducible innate defence responses and SA synthesis prior to subsequent pathogen-induced increases in ABA. Enhanced susceptibility due to loss of SA-mediated basal resistance is epistatically dominant over acquired resistance due to ABA deficiency, although ABA also contributes to symptom development. We conclude that pathogen-modulated ABA signalling rapidly antagonizes SA-mediated defences. We predict that hormonal perturbations, either induced or as a result of environmental stress, have a marked impact on pathological outcomes, and we provide a mechanistic basis for understanding priming events in plant defence.

A Plethora of Virulence Strategies Hidden Behind Nuclear Targeting of Microbial Effectors

PubMed Central

Rivas, Susana; Genin, Stéphane

2011-01-01

Plant immune responses depend on the ability to couple rapid recognition of the invading microbe to an efficient response. During evolution, plant pathogens have acquired the ability to deliver effector molecules inside host cells in order to manipulate cellular and molecular processes and establish pathogenicity. Following translocation into plant cells, microbial effectors may be addressed to different subcellular compartments. Intriguingly, a significant number of effector proteins from different pathogenic microorganisms, including viruses, oomycetes, fungi, nematodes, and bacteria, is targeted to the nucleus of host cells. In agreement with this observation, increasing evidence highlights the crucial role played by nuclear dynamics, and nucleocytoplasmic protein trafficking during a great variety of analyzed plant–pathogen interactions. Once in the nucleus, effector proteins are able to manipulate host transcription or directly subvert essential host components to promote virulence. Along these lines, it has been suggested that some effectors may affect histone packing and, thereby, chromatin configuration. In addition, microbial effectors may either directly activate transcription or target host transcription factors to alter their regular molecular functions. Alternatively, nuclear translocation of effectors may affect subcellular localization of their cognate resistance proteins in a process that is essential for resistance protein-mediated plant immunity. Here, we review recent progress in our field on the identification of microbial effectors that are targeted to the nucleus of host plant cells. In addition, we discuss different virulence strategies deployed by microbes, which have been uncovered through examination of the mechanisms that guide nuclear localization of effector proteins. PMID:22639625

'Order from disorder sprung': recognition and regulation in the immune system

NASA Astrophysics Data System (ADS)

Mak, Tak W.

2003-06-01

Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen threat is resolved. Once Paradise has been regained, memory cells remain in the body to sharply reduce the impact of a second exposure to a pathogen. Vaccination programs take advantage of this capacity of the human immune system for immunological memory, sparing millions the suffering associated with disease scourges. Thus does the order of the immune response spring from the disorder of pathogen attacks, and thus is Paradise preserved.

'Order from disorder sprung': recognition and regulation in the immune system.

PubMed

Mak, Tak W

2003-06-15

Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen threat is resolved. Once Paradise has been regained, memory cells remain in the body to sharply reduce the impact of a second exposure to a pathogen. Vaccination programs take advantage of this capacity of the human immune system for immunological memory, sparing millions the suffering associated with disease scourges. Thus does the order of the immune response spring from the disorder of pathogen attacks, and thus is Paradise preserved.

Analysis of the ZAR1 immune complex reveals determinants for immunity and molecular interactions

USDA-ARS?s Scientific Manuscript database

Plants depend on innate immunity to prevent disease. Plant pathogenic bacteria, like Pseudomonas syringae and Xanthomonas campestris, use the type III secretion system as a molecular syringe to inject type III secreted effector (T3SE) proteins in plants. The primary function of most T3SEs is to supp...

The Quantitative Basis of the Arabidopsis Innate Immune System to Endemic Pathogens Depends on Pathogen Genetics

PubMed Central

Corwin, Jason A.; Copeland, Daniel; Feusier, Julie; Subedy, Anushriya; Eshbaugh, Robert; Palmer, Christine; Maloof, Julin; Kliebenstein, Daniel J.

2016-01-01

The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B. cinerea, we identified a total of 2,982 genes associated with quantitative resistance using lesion area and 3,354 genes associated with camalexin production as measures of the interaction. Most genes were associated with resistance to a specific Botrytis isolate, which demonstrates the influence of pathogen genetic variation in analyzing host quantitative resistance. While known resistance genes, such as receptor-like kinases (RLKs) and nucleotide-binding site leucine-rich repeat proteins (NLRs), were found to be enriched among associated genes, they only account for a small fraction of the total genes associated with quantitative resistance. Using publically available co-expression data, we condensed the quantitative resistance associated genes into co-expressed gene networks. GO analysis of these networks implicated several biological processes commonly connected to disease resistance, including defense hormone signaling and ROS production, as well as novel processes, such as leaf development. Validation of single gene T-DNA knockouts in a Col-0 background demonstrate a high success rate (60%) when accounting for differences in environmental and Botrytis genetic variation. This study shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen genotypes. PMID:26866607

The Quantitative Basis of the Arabidopsis Innate Immune System to Endemic Pathogens Depends on Pathogen Genetics.

PubMed

Corwin, Jason A; Copeland, Daniel; Feusier, Julie; Subedy, Anushriya; Eshbaugh, Robert; Palmer, Christine; Maloof, Julin; Kliebenstein, Daniel J

2016-02-01

The most established model of the eukaryotic innate immune system is derived from examples of large effect monogenic quantitative resistance to pathogens. However, many host-pathogen interactions involve many genes of small to medium effect and exhibit quantitative resistance. We used the Arabidopsis-Botrytis pathosystem to explore the quantitative genetic architecture underlying host innate immune system in a population of Arabidopsis thaliana. By infecting a diverse panel of Arabidopsis accessions with four phenotypically and genotypically distinct isolates of the fungal necrotroph B. cinerea, we identified a total of 2,982 genes associated with quantitative resistance using lesion area and 3,354 genes associated with camalexin production as measures of the interaction. Most genes were associated with resistance to a specific Botrytis isolate, which demonstrates the influence of pathogen genetic variation in analyzing host quantitative resistance. While known resistance genes, such as receptor-like kinases (RLKs) and nucleotide-binding site leucine-rich repeat proteins (NLRs), were found to be enriched among associated genes, they only account for a small fraction of the total genes associated with quantitative resistance. Using publically available co-expression data, we condensed the quantitative resistance associated genes into co-expressed gene networks. GO analysis of these networks implicated several biological processes commonly connected to disease resistance, including defense hormone signaling and ROS production, as well as novel processes, such as leaf development. Validation of single gene T-DNA knockouts in a Col-0 background demonstrate a high success rate (60%) when accounting for differences in environmental and Botrytis genetic variation. This study shows that the genetic architecture underlying host innate immune system is extremely complex and is likely able to sense and respond to differential virulence among pathogen genotypes.

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

PubMed Central

de la Fuente, José; Antunes, Sandra; Bonnet, Sarah; Cabezas-Cruz, Alejandro; Domingos, Ana G.; Estrada-Peña, Agustín; Johnson, Nicholas; Kocan, Katherine M.; Mansfield, Karen L.; Nijhof, Ard M.; Papa, Anna; Rudenko, Nataliia; Villar, Margarita; Alberdi, Pilar; Torina, Alessandra; Ayllón, Nieves; Vancova, Marie; Golovchenko, Maryna; Grubhoffer, Libor; Caracappa, Santo; Fooks, Anthony R.; Gortazar, Christian; Rego, Ryan O. M.

2017-01-01

Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases. PMID:28439499

Phytohormone mediation of interactions between herbivores and plant pathogens.

PubMed

Lazebnik, Jenny; Frago, Enric; Dicke, Marcel; van Loon, Joop J A

2014-07-01

Induced plant defenses against either pathogens or herbivore attackers are regulated by phytohormones. These phytohormones are increasingly recognized as important mediators of interactions between organisms associated with plants. In this review, we discuss the role of plant defense hormones in sequential tri-partite interactions among plants, pathogenic microbes, and herbivorous insects, based on the most recent literature. We discuss the importance of pathogen trophic strategy in the interaction with herbivores that exhibit different feeding modes. Plant resistance mechanisms also affect plant quality in future interactions with attackers. We discuss exemplary evidence for the hypotheses that (i) biotrophic pathogens can facilitate chewing herbivores, unless plants exhibit effector-triggered immunity, but (ii) facilitate or inhibit phloem feeders. (iii) Necrotrophic pathogens, on the other hand, can inhibit both phloem feeders and chewers. We also propose herbivore feeding mode as predictor of effects on pathogens of different trophic strategies, providing evidence for the hypotheses that (iv) phloem feeders inhibit pathogen attack by increasing SA induction, whereas (v) chewing herbivores tend not to affect necrotrophic pathogens, while they may either inhibit or facilitate biotrophic pathogens. Putting these hypotheses to the test will increase our understanding of phytohormonal regulation of plant defense to sequential attack by plant pathogens and insect herbivores. This will provide valuable insight into plant-mediated ecological interactions among members of the plant-associated community.

Integrated multi-omic analyses in Biomphalaria-Schistosoma dialogue reveal the immunobiological significance of FREP-SmPoMuc interaction.

PubMed

Portet, Anaïs; Pinaud, Silvain; Tetreau, Guillaume; Galinier, Richard; Cosseau, Céline; Duval, David; Grunau, Christoph; Mitta, Guillaume; Gourbal, Benjamin

2017-10-01

The fresh water snail Biomphalaria glabrata is one of the vectors of the trematode pathogen Schistosoma mansoni, which is one of the agents responsible of human schistosomiasis. In this host-parasite interaction, co-evolutionary dynamic results into an infectivity mosaic known as compatibility polymorphism. Integrative approaches including large scale molecular approaches have been conducted in recent years to improve our understanding of the mechanisms underlying compatibility. This review presents the combination of integrated Multi-Omic approaches leading to the discovery of two repertoires of polymorphic and/or diversified interacting molecules: the parasite antigens S. mansoni polymorphic mucins (SmPoMucs) and the B. glabrata immune receptors fibrinogen-related proteins (FREPs). We argue that their interactions may be major components for defining the compatible/incompatible status of a specific snail/schistosome combination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploiting single-cell variability to infer the dynamics of immune responses

NASA Astrophysics Data System (ADS)

Höfer, Thomas

Cell division, differentiation, migration and death determine the dynamics of immune responses. These processes are regulated by a multitude of biochemical signals which, at present, cannot faithfully be reconstituted outside the living organism. However, quantitative measurements in living organisms have been limited. In recent years experimental techniques for the ``fate mapping'' of single immune cells have been developed that allow performing parallel single-cell experiments in an experimental animal. The resulting data are more informative about underlying biological processes than traditional measurements. I will show how the theory of stochastic dynamical systems can be used to infer the topology and dynamics of cell differentiation pathways from such data. The focus will be on joint theoretical and experimental work addressing: (i) the development of immune cells during hematopoiesis, and (ii) T cell responses to diverse pathogens. I will discuss questions on the nature of cellular variability that are posed by these new findings.

Protective and pathological immunity during CNS infections

PubMed Central

Klein, Robyn S.; Hunter, Christopher A.

2017-01-01

The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted the innate pathways that limit pathogen invasion of the CNS and that adaptive immunity mediates control of many neural infections. Because protective responses can result in bystander damage there are regulatory mechanisms that balance protective and pathological inflammation but which may also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege. PMID:28636958

Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies

PubMed Central

Suarez, Guadalupe Veronica; Vecchione, Maria Belen; Angerami, Matias Tomas; Sued, Omar; Bruttomesso, Andrea Claudia; Bottasso, Oscar Adelmo

2015-01-01

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients. PMID:26075241

Immunoendocrine interactions during HIV-TB coinfection: implications for the design of new adjuvant therapies.

PubMed

Suarez, Guadalupe Veronica; Vecchione, Maria Belen; Angerami, Matias Tomas; Sued, Omar; Bruttomesso, Andrea Claudia; Bottasso, Oscar Adelmo; Quiroga, Maria Florencia

2015-01-01

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients.

Can antibodies against flies alter malaria transmission in birds by changing vector behavior?

PubMed

Ghosh, Suma; Waite, Jessica L; Clayton, Dale H; Adler, Frederick R

2014-10-07

Transmission of insect-borne diseases is shaped by the interactions among parasites, vectors, and hosts. Any factor that alters movement of infected vectors from infected to uninfeced hosts will in turn alter pathogen spread. In this paper, we study one such pathogen-vector-host system, avian malaria in pigeons transmitted by fly ectoparasites, where both two-way and three-way interactions play a key role in shaping disease spread. Bird immune defenses against flies can decrease malaria prevalence by reducing fly residence time on infected birds or increase disease prevalence by enhancing fly movement and thus infection transmission. We develop a mathematical model that illustrates how these changes in vector behavior influence pathogen transmission and show that malaria prevalence is maximized at an intermediate level of defense avoidance by the flies. Understanding how host immune defenses indirectly alter disease transmission by influencing vector behavior has implications for reducing the transmission of human malaria and other vectored pathogens. Published by Elsevier Ltd.

Cytokinins for immunity beyond growth, galls and green islands.

PubMed

Naseem, Muhammad; Wölfling, Mirko; Dandekar, Thomas

2014-08-01

Cytokinins are essential plant hormones that control almost every aspect of plant growth and development. Their function in mediating plant susceptibility to fungal biotrophs and gall-causing pathogens is well known. Here we highlight the interaction between cytokinins and salicylic acid pathways. Furthermore, we discuss ways in which cytokinin signaling could crosstalk with plant immune networks. Some of these networks are modulated by pathogens to propagate disease, whereas others help the host to mitigate an infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune System

USDA-ARS?s Scientific Manuscript database

This review addresses important issues of porcine reproductive and respiratory syndrome virus (PRRSV) infection, immunity, pathogenesis and control. Worldwide PRRS is the most economically important infectious disease of pigs. We highlight the latest information on viral genome structure, pathogenic...

Insect antiviral innate immunity: pathways, effectors, and connections

PubMed Central

Kingsolver, Megan B.; Huang, Zhijing; Hardy, Richard W.

2014-01-01

Insects are infected by a wide array of viruses some of which are insect-restricted and pathogenic, and some of which are transmitted by biting insects to vertebrates. The medical and economic importance of these viruses heightens the need to understand the interaction between the infecting pathogen and the insect immune system in order to develop transmission interventions. The interaction of the virus with the insect host innate immune system plays a critical role in the outcome of infection. The major mechanism of antiviral defense is the siRNA pathway that responds through the detection of virus-derived dsRNA to suppress virus replication. However, other innate antimicrobial pathways such as Imd, Toll, Jak-STAT, and the autophagy pathway have also been shown to play important roles in antiviral immunity. In this review we provide an overview of the current understanding of the main insect antiviral pathways and examine recent findings that further our understanding of the roles of these pathways in facilitating a systemic and specific response to infecting viruses. PMID:24120681

Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF

PubMed Central

Felix, Jan; Kandiah, Eaazhisai; De Munck, Steven; Bloch, Yehudi; van Zundert, Gydo C.P.; Pauwels, Kris; Dansercoer, Ann; Novanska, Katka; Read, Randy J.; Bonvin, Alexandre M.J.J.; Vergauwen, Bjorn; Verstraete, Kenneth; Gutsche, Irina; Savvides, Savvas N.

2016-01-01

Subversion of the host immune system by viruses is often mediated by molecular decoys that sequester host proteins pivotal to mounting effective immune responses. The widespread mammalian pathogen parapox Orf virus deploys GIF, a member of the poxvirus immune evasion superfamily, to antagonize GM-CSF (granulocyte macrophage colony-stimulating factor) and IL-2 (interleukin-2), two pleiotropic cytokines of the mammalian immune system. However, structural and mechanistic insights into the unprecedented functional duality of GIF have remained elusive. Here we reveal that GIF employs a dimeric binding platform that sequesters two copies of its target cytokines with high affinity and slow dissociation kinetics to yield distinct complexes featuring mutually exclusive interaction footprints. We illustrate how GIF serves as a competitive decoy receptor by leveraging binding hotspots underlying the cognate receptor interactions of GM-CSF and IL-2, without sharing any structural similarity with the cytokine receptors. Our findings contribute to the tracing of novel molecular mimicry mechanisms employed by pathogenic viruses. PMID:27819269

Molecular Mechanisms of Innate Immune Inhibition by Non-Segmented Negative-Sense RNA Viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chatterjee, Srirupa; Basler, Christopher F.; Amarasinghe, Gaya K.

The host innate immune system serves as the first line of defense against viral infections. Germline-encoded pattern recognition receptors detect molecular patterns associated with pathogens and activate innate immune responses. Of particular relevance to viral infections are those pattern recognition receptors that activate type I interferon responses, which establish an antiviral state. The order Mononegavirales is composed of viruses that possess single-stranded, non-segmented negative-sense (NNS) RNA genomes and are important human pathogens that consistently antagonize signaling related to type I interferon responses. NNS viruses have limited encoding capacity compared to many DNA viruses, and as a likely consequence, most openmore » reading frames encode multifunctional viral proteins that interact with host factors in order to evade host cell defenses while promoting viral replication. In this review, we will discuss the molecular mechanisms of innate immune evasion by select NNS viruses. A greater understanding of these interactions will be critical in facilitating the development of effective therapeutics and viral countermeasures.« less

A Plant Immune Receptor Detects Pathogen Effectors that Target WRKY Transcription Factors.

PubMed

Sarris, Panagiotis F; Duxbury, Zane; Huh, Sung Un; Ma, Yan; Segonzac, Cécile; Sklenar, Jan; Derbyshire, Paul; Cevik, Volkan; Rallapalli, Ghanasyam; Saucet, Simon B; Wirthmueller, Lennart; Menke, Frank L H; Sohn, Kee Hoon; Jones, Jonathan D G

2015-05-21

Defense against pathogens in multicellular eukaryotes depends on intracellular immune receptors, yet surveillance by these receptors is poorly understood. Several plant nucleotide-binding, leucine-rich repeat (NB-LRR) immune receptors carry fusions with other protein domains. The Arabidopsis RRS1-R NB-LRR protein carries a C-terminal WRKY DNA binding domain and forms a receptor complex with RPS4, another NB-LRR protein. This complex detects the bacterial effectors AvrRps4 or PopP2 and then activates defense. Both bacterial proteins interact with the RRS1 WRKY domain, and PopP2 acetylates lysines to block DNA binding. PopP2 and AvrRps4 interact with other WRKY domain-containing proteins, suggesting these effectors interfere with WRKY transcription factor-dependent defense, and RPS4/RRS1 has integrated a "decoy" domain that enables detection of effectors that target WRKY proteins. We propose that NB-LRR receptor pairs, one member of which carries an additional protein domain, enable perception of pathogen effectors whose function is to target that domain. Copyright © 2015 Elsevier Inc. All rights reserved.

Thermal Stress Triggers Broad Pocillopora damicornis Transcriptomic Remodeling, while Vibrio coralliilyticus Infection Induces a More Targeted Immuno-Suppression Response

PubMed Central

Vidal-Dupiol, Jeremie; Dheilly, Nolwenn M.; Rondon, Rodolfo; Grunau, Christoph; Cosseau, Céline; Smith, Kristina M.; Freitag, Michael; Adjeroud, Mehdi; Mitta, Guillaume

2014-01-01

Global change and its associated temperature increase has directly or indirectly changed the distributions of hosts and pathogens, and has affected host immunity, pathogen virulence and growth rates. This has resulted in increased disease in natural plant and animal populations worldwide, including scleractinian corals. While the effects of temperature increase on immunity and pathogen virulence have been clearly identified, their interaction, synergy and relative weight during pathogenesis remain poorly documented. We investigated these phenomena in the interaction between the coral Pocillopora damicornis and the bacterium Vibrio coralliilyticus, for which the infection process is temperature-dependent. We developed an experimental model that enabled unraveling the effects of thermal stress, and virulence vs. non-virulence of the bacterium. The physiological impacts of various treatments were quantified at the transcriptome level using a combination of RNA sequencing and targeted approaches. The results showed that thermal stress triggered a general weakening of the coral, making it more prone to infection, non-virulent bacterium induced an ‘efficient’ immune response, whereas virulent bacterium caused immuno-suppression in its host. PMID:25259845

The RhoGAP SPIN6 Associates with SPL11 and OsRac1 and Negatively Regulates Programmed Cell Death and Innate Immunity in Rice

PubMed Central

Liu, Jinling; Park, Chan Ho; He, Feng; Nagano, Minoru; Wang, Mo; Bellizzi, Maria; Zhang, Kai; Zeng, Xiaoshan; Liu, Wende; Ning, Yuese; Kawano, Yoji; Wang, Guo-Liang

2015-01-01

The ubiquitin proteasome system in plants plays important roles in plant-microbe interactions and in immune responses to pathogens. We previously demonstrated that the rice U-box E3 ligase SPL11 and its Arabidopsis ortholog PUB13 negatively regulate programmed cell death (PCD) and defense response. However, the components involved in the SPL11/PUB13-mediated PCD and immune signaling pathway remain unknown. In this study, we report that SPL11-interacting Protein 6 (SPIN6) is a Rho GTPase-activating protein (RhoGAP) that interacts with SPL11 in vitro and in vivo. SPL11 ubiquitinates SPIN6 in vitro and degrades SPIN6 in vivo via the 26S proteasome-dependent pathway. Both RNAi silencing in transgenic rice and knockout of Spin6 in a T-DNA insertion mutant lead to PCD and increased resistance to the rice blast pathogen Magnaporthe oryzae and the bacterial blight pathogen Xanthomonas oryzae pv. oryzae. The levels of reactive oxygen species and defense-related gene expression are significantly elevated in both the Spin6 RNAi and mutant plants. Strikingly, SPIN6 interacts with the small GTPase OsRac1, catalyze the GTP-bound OsRac1 into the GDP-bound state in vitro and has GAP activity towards OsRac1 in rice cells. Together, our results demonstrate that the RhoGAP SPIN6 acts as a linkage between a U-box E3 ligase-mediated ubiquitination pathway and a small GTPase-associated defensome system for plant immunity. PMID:25658451

Linking genetic and environmental factors in amphibian disease risk

PubMed Central

Savage, Anna E; Becker, Carlos G; Zamudio, Kelly R

2015-01-01

A central question in evolutionary biology is how interactions between organisms and the environment shape genetic differentiation. The pathogen Batrachochytrium dendrobatidis (Bd) has caused variable population declines in the lowland leopard frog (Lithobates yavapaiensis); thus, disease has potentially shaped, or been shaped by, host genetic diversity. Environmental factors can also influence both amphibian immunity and Bd virulence, confounding our ability to assess the genetic effects on disease dynamics. Here, we used genetics, pathogen dynamics, and environmental data to characterize L. yavapaiensis populations, estimate migration, and determine relative contributions of genetic and environmental factors in predicting Bd dynamics. We found that the two uninfected populations belonged to a single genetic deme, whereas each infected population was genetically unique. We detected an outlier locus that deviated from neutral expectations and was significantly correlated with mortality within populations. Across populations, only environmental variables predicted infection intensity, whereas environment and genetics predicted infection prevalence, and genetic diversity alone predicted mortality. At one locality with geothermally elevated water temperatures, migration estimates revealed source–sink dynamics that have likely prevented local adaptation. We conclude that integrating genetic and environmental variation among populations provides a better understanding of Bd spatial epidemiology, generating more effective conservation management strategies for mitigating amphibian declines. PMID:26136822

Exploring NAD+ metabolism in host-pathogen interactions.

PubMed

Mesquita, Inês; Varela, Patrícia; Belinha, Ana; Gaifem, Joana; Laforge, Mireille; Vergnes, Baptiste; Estaquier, Jérôme; Silvestre, Ricardo

2016-03-01

Nicotinamide adenine dinucleotide (NAD(+)) is a vital molecule found in all living cells. NAD(+) intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD(+) metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD(+) metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD(+) homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD(+) or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD(+) metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases.

PAMPs, PRRs, effectors and R-genes associated with citrus–pathogen interactions

PubMed Central

Dalio, Ronaldo J. D.; Magalhães, Diogo M.; Rodrigues, Carolina M.; Arena, Gabriella D.; Oliveira, Tiago S.; Souza-Neto, Reinaldo R.; Picchi, Simone C.; Martins, Paula M. M.; Santos, Paulo J. C.; Maximo, Heros J.; Pacheco, Inaiara S.; De Souza, Alessandra A.

2017-01-01

Abstract Background Recent application of molecular-based technologies has considerably advanced our understanding of complex processes in plant–pathogen interactions and their key components such as PAMPs, PRRs, effectors and R-genes. To develop novel control strategies for disease prevention in citrus, it is essential to expand and consolidate our knowledge of the molecular interaction of citrus plants with their pathogens. Scope This review provides an overview of our understanding of citrus plant immunity, focusing on the molecular mechanisms involved in the interactions with viruses, bacteria, fungi, oomycetes and vectors related to the following diseases: tristeza, psorosis, citrus variegated chlorosis, citrus canker, huanglongbing, brown spot, post-bloom, anthracnose, gummosis and citrus root rot. PMID:28065920

The varieties of immunological experience: of pathogens, stress, and dendritic cells.

PubMed

Pulendran, Bali

2015-01-01

In the 40 years since their discovery, dendritic cells (DCs) have been recognized as central players in immune regulation. DCs sense microbial stimuli through pathogen-recognition receptors (PRRs) and decode, integrate, and present information derived from such stimuli to T cells, thus stimulating immune responses. DCs can also regulate the quality of immune responses. Several functionally specialized subsets of DCs exist, but DCs also display functional plasticity in response to diverse stimuli. In addition to sensing pathogens via PRRs, emerging evidence suggests that DCs can also sense stress signals, such as amino acid starvation, through ancient stress and nutrient sensing pathways, to stimulate adaptive immunity. Here, I discuss these exciting advances in the context of a historic perspective on the discovery of DCs and their role in immune regulation. I conclude with a discussion of emerging areas in DC biology in the systems immunology era and suggest that the impact of DCs on immunity can be usefully contextualized in a hierarchy-of-organization model in which DCs, their receptors and signaling networks, cell-cell interactions, tissue microenvironment, and the host macroenvironment represent different levels of the hierarchy. Immunity or tolerance can then be represented as a complex function of each of these hierarchies.

The role of the microbiota in shaping infectious immunity

PubMed Central

Hand, Timothy W.

2016-01-01

Humans are meta-organisms that maintain a diverse population of microorganisms on their barrier surfaces, collectively named the microbiota. Since most pathogens either cross or inhabit barrier surfaces, the microbiota plays a critical and often protective role during infections, both by modulating immune system responses and by mediating colonization resistance. However, the microbiota can also act as a reservoir for opportunistic micro-organisms that can ‘bloom’, significantly complicating diseases of barrier surfaces by contributing to inflammatory immune responses. Here, we review our current understanding of the complex interactions between the host, its microbiota and pathogenic organisms, focusing in particular on the intestinal mucosa. PMID:27616558

A Review of the Interactions between Wheat and Wheat Pathogens: Zymoseptoria tritici, Fusarium spp. and Parastagonospora nodorum

PubMed Central

Duba, Adrian; Goriewa-Duba, Klaudia; Wachowska, Urszula

2018-01-01

Zymoseptoria tritici is a hemibiotrophic pathogen which causes Septoria leaf blotch in wheat. The pathogenesis of the disease consists of a biotrophic phase and a necrotrophic phase. The pathogen infects the host plant by suppressing its immune response in the first stage of infection. Hemibiotrophic pathogens of the genus Fusarium cause Fusarium head blight, and the necrotrophic Parastagonospora nodorum is responsible for Septoria nodorum blotch in wheat. Cell wall-degrading enzymes in plants promote infections by necrotrophic and hemibiotrophic pathogens, and trichothecenes, secondary fungal metabolites, facilitate infections caused by fungi of the genus Fusarium. There are no sources of complete resistance to the above pathogens in wheat. Defense mechanisms in wheat are controlled by many genes encoding resistance traits. In the wheat genome, the characteristic features of loci responsible for resistance to pathogenic infections indicate that at least several dozen genes encode resistance to pathogens. The molecular interactions between wheat and Z. tritici, P. nodorum and Fusarium spp. pathogens have been insufficiently investigated. Most studies focus on the mechanisms by which the hemibiotrophic Z. tritici suppresses immune responses in plants and the role of mycotoxins and effector proteins in infections caused by P. nodorum and Fusarium spp. fungi. Trichothecene glycosylation and effector proteins, which are involved in defense responses in wheat, have been described at the molecular level. Recent advances in molecular biology have produced interesting findings which should be further elucidated in studies of molecular interactions between wheat and fungal pathogens. The Clustered Regularly-Interspaced Short Palindromic Repeats/ CRISPR associated (CRISPR/Cas) system can be used to introduce targeted mutations into the wheat genome and confer resistance to selected fungal diseases. Host-induced gene silencing and spray-induced gene silencing are also useful tools for analyzing wheat–pathogens interactions which can be used to develop new strategies for controlling fungal diseases. PMID:29642627

Recent insights into host-pathogen interaction in white spot syndrome virus infected penaeid shrimp.

PubMed

Shekhar, M S; Ponniah, A G

2015-07-01

Viral disease outbreaks are a major concern impeding the development of the shrimp aquaculture industry. The viral disease due to white spot syndrome virus (WSSV) observed in early 1990s still continues unabated affecting the shrimp farms and cause huge economic loss to the shrimp aquaculture industry. In the absence of effective therapeutics to control WSSV, it is important to understand viral pathogenesis and shrimp response to WSSV at the molecular level. Identification and molecular characterization of WSSV proteins and receptors may facilitate in designing and development of novel therapeutics and antiviral drugs that may inhibit viral replication. Investigations into host-pathogen interactions might give new insights to viral infectivity, tissue tropism and defence mechanism elicited in response to WSSV infection. However, due to the limited information on WSSV gene function and host immune response, the signalling pathways which are associated in shrimp pathogen interaction have also not been elucidated completely. In the present review, the focus is on those shrimp proteins and receptors that are potentially involved in virus infection or in the defence mechanism against WSSV. In addition, the major signalling pathways involved in the innate immune response and the role of apoptosis in host-pathogen interaction is discussed. © 2014 John Wiley & Sons Ltd.

High rate of adaptation of mammalian proteins that interact with Plasmodium and related parasites

PubMed Central

Telis, Natalie; Petrov, Dmitri A.

2017-01-01

Plasmodium parasites, along with their Piroplasm relatives, have caused malaria-like illnesses in terrestrial mammals for millions of years. Several Plasmodium-protective alleles have recently evolved in human populations, but little is known about host adaptation to blood parasites over deeper evolutionary timescales. In this work, we analyze mammalian adaptation in ~500 Plasmodium- or Piroplasm- interacting proteins (PPIPs) manually curated from the scientific literature. We show that (i) PPIPs are enriched for both immune functions and pleiotropy with other pathogens, and (ii) the rate of adaptation across mammals is significantly elevated in PPIPs, compared to carefully matched control proteins. PPIPs with high pathogen pleiotropy show the strongest signatures of adaptation, but this pattern is fully explained by their immune enrichment. Several pieces of evidence suggest that blood parasites specifically have imposed selection on PPIPs. First, even non-immune PPIPs that lack interactions with other pathogens have adapted at twice the rate of matched controls. Second, PPIP adaptation is linked to high expression in the liver, a critical organ in the parasite life cycle. Finally, our detailed investigation of alpha-spectrin, a major red blood cell membrane protein, shows that domains with particularly high rates of adaptation are those known to interact specifically with P. falciparum. Overall, we show that host proteins that interact with Plasmodium and Piroplasm parasites have experienced elevated rates of adaptation across mammals, and provide evidence that some of this adaptation has likely been driven by blood parasites. PMID:28957326

Chlamydia trachomatis Cellular Exit Alters Interactions with Host Dendritic Cells

PubMed Central

Sherrid, Ashley M.

2017-01-01

ABSTRACT The strategies utilized by pathogens to exit host cells are an area of pathogenesis which has received surprisingly little attention, considering the necessity of this step for infections to propagate. Even less is known about how exit through these pathways affects downstream host-pathogen interactions and the generation of an immune response. Chlamydia trachomatis exits host epithelial cells through two equally active mechanisms: lysis and extrusion. Studies have characterized the outcome of interactions between host innate immune cells, such as dendritic cells and macrophages, and free, extracellular Chlamydia bacteria, such as those resulting from lysis. Exit via extrusion generates a distinct, host-membrane-bound compartment of Chlamydia separate from the original infected cell. In this study, we assessed the effect of containment within extrusions upon the interaction between Chlamydia and host dendritic cells. Extrusion dramatically affected the outcome of Chlamydia-dendritic cell interactions for both the bacterium and the host cell. Dendritic cells rapidly underwent apoptosis in response to engulfment of an extrusion, while uptake of an equivalent dose of free Chlamydia had no such effect. Containment within an extrusion also prolonged bacterial survival within dendritic cells and altered the initial innate immune signaling by the dendritic cell. PMID:28223346

What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae?

PubMed Central

Colijn, Caroline; Cohen, Ted; Fraser, Christophe; Hanage, William; Goldstein, Edward; Givon-Lavi, Noga; Dagan, Ron; Lipsitch, Marc

2010-01-01

The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance. PMID:19940002

Targeting of the hydrophobic metabolome by pathogens.

PubMed

Helms, J Bernd; Kaloyanova, Dora V; Strating, Jeroen R P; van Hellemond, Jaap J; van der Schaar, Hilde M; Tielens, Aloysius G M; van Kuppeveld, Frank J M; Brouwers, Jos F

2015-05-01

The hydrophobic molecules of the metabolome - also named the lipidome - constitute a major part of the entire metabolome. Novel technologies show the existence of a staggering number of individual lipid species, the biological functions of which are, with the exception of only a few lipid species, unknown. Much can be learned from pathogens that have evolved to take advantage of the complexity of the lipidome to escape the immune system of the host organism and to allow their survival and replication. Different types of pathogens target different lipids as shown in interaction maps, allowing visualization of differences between different types of pathogens. Bacterial and viral pathogens target predominantly structural and signaling lipids to alter the cellular phenotype of the host cell. Fungal and parasitic pathogens have complex lipidomes themselves and target predominantly the release of polyunsaturated fatty acids from the host cell lipidome, resulting in the generation of eicosanoids by either the host cell or the pathogen. Thus, whereas viruses and bacteria induce predominantly alterations in lipid metabolites at the host cell level, eukaryotic pathogens focus on interference with lipid metabolites affecting systemic inflammatory reactions that are part of the immune system. A better understanding of the interplay between host-pathogen interactions will not only help elucidate the fundamental role of lipid species in cellular physiology, but will also aid in the generation of novel therapeutic drugs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interacting epidemics on overlay networks

NASA Astrophysics Data System (ADS)

Funk, Sebastian; Jansen, Vincent A. A.

2010-03-01

The interaction between multiple pathogens spreading on networks connecting a given set of nodes presents an ongoing theoretical challenge. Here, we aim to understand such interactions by studying bond percolation of two different processes on overlay networks of arbitrary joint degree distribution. We find that an outbreak of a first pathogen providing immunity to another one spreading subsequently on a second network connecting the same set of nodes does so most effectively if the degrees on the two networks are positively correlated. In that case, the protection is stronger the more heterogeneous the degree distributions of the two networks are. If, on the other hand, the degrees are uncorrelated or negatively correlated, increasing heterogeneity reduces the potential of the first process to prevent the second one from reaching epidemic proportions. We generalize these results to cases where the edges of the two networks overlap to arbitrary amount, or where the immunity granted is only partial. If both processes grant immunity to each other, we find a wide range of possible situations of coexistence or mutual exclusion, depending on the joint degree distribution of the underlying networks and the amount of immunity granted mutually. These results generalize the concept of a coexistence threshold and illustrate the impact of large-scale network structure on the interaction between multiple spreading agents.

Borrelia burgdorferi Keeps Moving and Carries on: A Review of Borrelial Dissemination and Invasion

PubMed Central

Hyde, Jenny A.

2017-01-01

Borrelia burgdorferi is the etiological agent of Lyme disease, a multisystemic, multistage, inflammatory infection resulting in patients experiencing cardiac, neurological, and arthritic complications when not treated with antibiotics shortly after exposure. The spirochetal bacterium transmits through the Ixodes vector colonizing the dermis of a mammalian host prior to hematogenous dissemination and invasion of distal tissues all the while combating the immune response as it traverses through its pathogenic lifecycle. The innate immune response controls the borrelial burden in the dermis, but is unable to clear the infection and thereby prevent progression of disease. Dissemination in the mammalian host requires temporal regulation of virulence determinants to allow for vascular interactions, invasion, and colonization of distal tissues. Virulence determinants and/or adhesins are highly heterogenetic among environmental B. burgdorferi strains with particular genotypes being associated with the ability to disseminate to specific tissues and the severity of disease, but fail to generate cross-protective immunity between borrelial strains. The unique motility of B. burgdorferi rendered by the endoflagella serves a vital function for dissemination and protection from immune recognition. Progress has been made toward understanding the chemotactic regulation coordinating the activity of the two polar localized flagellar motors and their role in borrelial virulence, but this regulation is not yet fully understood. Distinct states of motility allow for dynamic interactions between several B. burgdorferi adhesins and host targets that play roles in transendothelial migration. Transmigration across endothelial and blood–brain barriers allows for the invasion of tissues and elicits localized immune responses. The invasive nature of B. burgdorferi is lacking in proactive mechanisms to modulate disease, such as secretion systems and toxins, but recent work has shown degradation of host extracellular matrices by B. burgdorferi contributes to the invasive capabilities of the pathogen. Additionally, B. burgdorferi may use invasion of eukaryotic cells for immune evasion and protection against environmental stresses. This review provides an overview of B. burgdorferi mechanisms for dissemination and invasion in the mammalian host, which are essential for pathogenesis and the development of persistent infection. PMID:28270812

Evolutionary genetics of insect innate immunity.

PubMed

Viljakainen, Lumi

2015-11-01

Patterns of evolution in immune defense genes help to understand the evolutionary dynamics between hosts and pathogens. Multiple insect genomes have been sequenced, with many of them having annotated immune genes, which paves the way for a comparative genomic analysis of insect immunity. In this review, I summarize the current state of comparative and evolutionary genomics of insect innate immune defense. The focus is on the conserved and divergent components of immunity with an emphasis on gene family evolution and evolution at the sequence level; both population genetics and molecular evolution frameworks are considered. © The Author 2015. Published by Oxford University Press.

Human pathogenic bacteria, fungi, and viruses in Drosophila

PubMed Central

Panayidou, Stavria; Ioannidou, Eleni; Apidianakis, Yiorgos

2014-01-01

Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila–microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection. PMID:24398387

Envelope Structures of Gram-Positive Bacteria

PubMed Central

Rajagopal, Mithila; Walker, Suzanne

2016-01-01

Gram-positive organisms, including the pathogens Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis, have dynamic cell envelopes that mediate interactions with the environment and serve as the first line of defense against toxic molecules. Major components of the cell envelope include peptidoglycan, which is a well-established target for antibiotics, teichoic acids, capsular polysaccharides, surface proteins, and phospholipids. These components can undergo modification to promote pathogenesis, decrease susceptibility to antibiotics and host immune defenses, and enhance survival in hostile environments. This chapter will cover the structure, biosynthesis and important functions of major cell envelope components in Gram-positive bacteria. Possible targets for new antimicrobials will be noted. PMID:26919863

Protective and Pathological Immunity during Central Nervous System Infections.

PubMed

Klein, Robyn S; Hunter, Christopher A

2017-06-20

The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege. Copyright © 2017. Published by Elsevier Inc.

Immune system responses and fitness costs associated with consumption of bacteria in larvae of Trichoplusia ni

PubMed Central

Freitak, Dalial; Wheat, Christopher W; Heckel, David G; Vogel, Heiko

2007-01-01

Background Insects helped pioneer, and persist as model organisms for, the study of specific aspects of immunity. Although they lack an adaptive immune system, insects possess an innate immune system that recognizes and destroys intruding microorganisms. Its operation under natural conditions has not been well studied, as most studies have introduced microbes to laboratory-reared insects via artificial mechanical wounding. One of the most common routes of natural exposure and infection, however, is via food; thus, the role of dietary microbial communities in herbivorous insect immune system evolution invites study. Here, we examine the immune system response and consequences of exposing a lepidopteran agricultural pest to non-infectious microorganisms via simple oral consumption. Results Immune system response was compared between Trichoplusia ni larvae reared on diets with or without non-pathogenic bacteria (Escherichia coli and Micrococcus luteus). Two major immune response-related enzymatic activities responded to diets differently – phenoloxidase activity was inhibited in the bacteria-fed larvae, whereas general antibacterial activity was enhanced. Eight proteins were highly expressed in the hemolymph of the bacteria fed larvae, among them immune response related proteins arylphorin, apolipophorin III and gloverin. Expression response among 25 putative immune response-related genes were assayed via RT-qPCR. Seven showed more than fivefold up regulation in the presence of bacterial diet, with 22 in total being differentially expressed, among them apolipophorin III, cecropin, gallerimycin, gloverin, lysozyme, and phenoloxidase inhibiting enzyme. Finally, potential life-history trade-offs were studied, with pupation time and pupal mass being negatively affected in bacteria fed larvae. Conclusion The presence of bacteria in food, even if non-pathogenic, can trigger an immune response cascade with life history tradeoffs. Trichoplusia ni larvae are able to detect and respond to environmental microbes encountered in the diet, possibly even using midgut epithelial tissue as a sensing organ. Potential benefits of this immune system priming may outweigh the observed tradeoffs, as priming based on environmentally sensed bacterial may decrease risk of serious infection. These results show that food plant microbial communities represent a dynamic and unstudied part of the coevolutionary interactions between plants and their insect herbivores. PMID:18154650

Staphylococcal Immune Evasion Proteins: Structure, Function, and Host Adaptation.

PubMed

Koymans, Kirsten J; Vrieling, Manouk; Gorham, Ronald D; van Strijp, Jos A G

2017-01-01

Staphylococcus aureus is a successful human and animal pathogen. Its pathogenicity is linked to its ability to secrete a large amount of virulence factors. These secreted proteins interfere with many critical components of the immune system, both innate and adaptive, and hamper proper immune functioning. In recent years, numerous studies have been conducted in order to understand the molecular mechanism underlying the interaction of evasion molecules with the host immune system. Structural studies have fundamentally contributed to our understanding of the mechanisms of action of the individual factors. Furthermore, such studies revealed one of the most striking characteristics of the secreted immune evasion molecules: their conserved structure. Despite high-sequence variability, most immune evasion molecules belong to a small number of structural categories. Another remarkable characteristic is that S. aureus carries most of these virulence factors on mobile genetic elements (MGE) or ex-MGE in its accessory genome. Coevolution of pathogen and host has resulted in immune evasion molecules with a highly host-specific function and prevalence. In this review, we explore how these shared structures and genomic locations relate to function and host specificity. This is discussed in the context of therapeutic options for these immune evasion molecules in infectious as well as in inflammatory diseases.

Recent progress in understanding host immune response to Avian Coccidiosis: Th1 and Th17 responses

USDA-ARS?s Scientific Manuscript database

Host-pathogen interaction leading to protection against coccidiosis is complex, involving many aspects of innate and adaptive immunity to intracellular parasites. The etiologic agent of avian coccidiosis is Eimeria, a genus of eukaryotic obligate intracellular parasites belonging to the phylum Apico...

Epidemiological determinants of successful vaccine development.

PubMed

Nishiura, Hiroshi; Mizumoto, Kenji

2013-01-01

Epidemiological determinants of successful vaccine development were explored using measurable biological variables including antigenic stability and requirement of T-cell immunity. Employing a logistic regression model, we demonstrate that a high affinity with blood and immune cells and pathogen interactions (e.g. interference) would be the risk factors of failure for vaccine development.

Plants and pathogens: putting infection strategies and defence mechanisms on the map.

PubMed

Faulkner, Christine; Robatzek, Silke

2012-12-01

All plant organs are vulnerable to colonisation and molecular manipulation by microbes. When this interaction allows proliferation of the microbe at the expense of the host, the microbe can be described as a pathogen. In our attempts to understand the full nature of the interactions that occur between a potential pathogen and its host, various aspects of the molecular mechanisms of infection and defence have begun to be characterised. There is significant variation in these mechanisms. While previous research has examined plant-pathogen interactions with whole plant/organ resolution, the specificity of infection strategies and changes in both gene expression and protein localisation of immune receptors upon infection suggest there is much to be gained from examination of plant-microbe interactions at the cellular level. Copyright © 2012 Elsevier Ltd. All rights reserved.

Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts

DOE PAGES

Paull, Sara H.; Horton, Daniel E.; Ashfaq, Moetasim; ...

2017-02-08

The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We foundmore » that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. Lastly, these results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases.« less

Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts

PubMed Central

Horton, Daniel E.; Ashfaq, Moetasim; Rastogi, Deeksha; Kramer, Laura D.; Diffenbaugh, Noah S.

2017-01-01

The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We found that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. These results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases. PMID:28179512

Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paull, Sara H.; Horton, Daniel E.; Ashfaq, Moetasim

The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We foundmore » that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. Lastly, these results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases.« less

Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts.

PubMed

Paull, Sara H; Horton, Daniel E; Ashfaq, Moetasim; Rastogi, Deeksha; Kramer, Laura D; Diffenbaugh, Noah S; Kilpatrick, A Marm

2017-02-08

The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We found that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. These results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases. © 2017 The Author(s).

Histoplasma capsulatum α-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor

PubMed Central

Rappleye, Chad A.; Eissenberg, Linda Groppe; Goldman, William E.

2007-01-01

Successful infection by fungal pathogens depends on subversion of host immune mechanisms that detect conserved cell wall components such as β-glucans. A less common polysaccharide, α-(1,3)-glucan, is a cell wall constituent of most fungal respiratory pathogens and has been correlated with pathogenicity or linked directly to virulence. However, the precise mechanism by which α-(1,3)-glucan promotes fungal virulence is unknown. Here, we show that α-(1,3)-glucan is present in the outermost layer of the Histoplasma capsulatum yeast cell wall and contributes to pathogenesis by concealing immunostimulatory β-glucans from detection by host phagocytic cells. Production of proinflammatory TNFα by phagocytes was suppressed either by the presence of the α-(1,3)-glucan layer on yeast cells or by RNA interference based depletion of the host β-glucan receptor dectin-1. Thus, we have functionally defined key molecular components influencing the initial host–pathogen interaction in histoplasmosis and have revealed an important mechanism by which H. capsulatum thwarts the host immune system. Furthermore, we propose that the degree of this evasion contributes to the difference in pathogenic potential between dimorphic fungal pathogens and opportunistic fungi. PMID:17227865

The mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging.

PubMed

Coles, Jonathan A; Stewart-Hutchinson, Phillip J; Myburgh, Elmarie; Brewer, James M

2017-08-15

A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. Hence observation of these regions has wide application to understanding host-pathogen interactions. Interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with their unsupported membranes, invasive dissection can alter the tissue architecture. For these reasons, intravital imaging through the unperforated skull is the method of choice. We give a protocol for a simple method of two-photon microscopy through the thinned cortical skull of the anesthetized mouse to enable real-time imaging with sub-micron resolution through the meninges and into the superficial brain parenchyma. In reporter mice in which selected cell types express fluorescent proteins, imaging after infection with fluorescent pathogens (lymphocytic choriomeningitis virus, Trypanosoma brucei or Plasmodium berghei) has shown strong recruitment to the cortical meninges of immune cells, including neutrophils, T cells, and putative dendritic cells and macrophages. Without special labeling, the boundaries between the dura mater, the leptomeninx, and the parenchyma are not directly visualized in intravital two-photon microscopy, but other landmarks and characteristics, which we illustrate, allow the researcher to identify the compartment being imaged. While most infectious meningitides are localized mainly in the dura mater, others involve recruitment of immune cells to the leptomeninx. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Role of vaccination-induced immunity and antigenic distance in the transmission dynamics of highly pathogenic avian influenza H5N1

PubMed Central

Rousou, Xanthoula; Kalthoff, Donata; Beer, Martin

2016-01-01

Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds. PMID:26763336

Dose-dependent effects of an immune challenge at both ultimate and proximate levels in Drosophila melanogaster.

PubMed

Nystrand, M; Dowling, D K

2014-05-01

Immune responses are highly dynamic. The magnitude and efficiency of an immune response to a pathogen can change markedly across individuals, and such changes may be influenced by variance in a range of intrinsic (e.g. age, genotype, sex) and external (e.g. abiotic stress, pathogen identity, strain) factors. Life history theory predicts that up-regulation of the immune system will come at a physiological cost, and studies have confirmed that increased investment in immunity can reduce reproductive output and survival. Furthermore, males and females often have divergent reproductive strategies, and this might drive the evolution of sex-specific life history trade-offs involving immunity, and sexual dimorphism in immune responses per se. Here, we employ an experiment design to elucidate dose-dependent and sex-specific responses to exposure to a nonpathogenic immune elicitor at two scales--the 'ultimate' life history and the underlying 'proximate' immune level in Drosophila melanogaster. We found dose-dependent effects of immune challenges on both male and female components of reproductive success, but not on survival, as well as a response in antimicrobial activity. These results indicate that even in the absence of the direct pathogenic effects that are associated with actual disease, individual life histories respond to a perceived immune challenge--but with the magnitude of this response being contingent on the initial dose of exposure. Furthermore, the results indicate that immune responses at the ultimate life history level may indeed reflect underlying processes that occur at the proximate level. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Deciphering the landscape of host barriers to Listeria monocytogenes infection.

PubMed

Zhang, Ting; Abel, Sören; Abel Zur Wiesch, Pia; Sasabe, Jumpei; Davis, Brigid M; Higgins, Darren E; Waldor, Matthew K

2017-06-13

Listeria monocytogenes is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate L monocytogenes population dynamics during infection. We created a genetically barcoded library of murinized L monocytogenes and then used deep sequencing to track the pathogen's dissemination routes and quantify its founding population ( N b ) sizes in different organs. We found that the pathogen disseminates from the gastrointestinal tract to distal sites through multiple independent routes and that N b sizes vary greatly among tissues, indicative of diverse host barriers to infection. Unexpectedly, comparative analyses of sequence tags revealed that fecally excreted organisms are largely derived from the very small number of L. monocytogenes cells that colonize the gallbladder. Immune depletion studies suggest that distinct innate immune cells restrict the pathogen's capacity to establish replicative niches in the spleen and liver. Finally, studies in germ-free mice suggest that the microbiota plays a critical role in the development of the splenic, but not the hepatic, barriers that prevent L. monocytogenes from seeding these organs. Collectively, these observations illustrate the potency of the STAMP approach to decipher the impact of host factors on population dynamics of pathogens during infection.

Death don't have no mercy and neither does calcium: Arabidopsis CYCLIC NUCLEOTIDE GATED CHANNEL2 and innate immunity.

PubMed

Ali, Rashid; Ma, Wei; Lemtiri-Chlieh, Fouad; Tsaltas, Dimitrios; Leng, Qiang; von Bodman, Susannne; Berkowitz, Gerald A

2007-03-01

Plant innate immune response to pathogen infection includes an elegant signaling pathway leading to reactive oxygen species generation and resulting hypersensitive response (HR); localized programmed cell death in tissue surrounding the initial infection site limits pathogen spread. A veritable symphony of cytosolic signaling molecules (including Ca(2+), nitric oxide [NO], cyclic nucleotides, and calmodulin) have been suggested as early components of HR signaling. However, specific interactions among these cytosolic secondary messengers and their roles in the signal cascade are still unclear. Here, we report some aspects of how plants translate perception of a pathogen into a signal cascade leading to an innate immune response. We show that Arabidopsis thaliana CYCLIC NUCLEOTIDE GATED CHANNEL2 (CNGC2/DND1) conducts Ca(2+) into cells and provide a model linking this Ca(2+) current to downstream NO production. NO is a critical signaling molecule invoking plant innate immune response to pathogens. Plants without functional CNGC2 lack this cell membrane Ca(2+) current and do not display HR; providing the mutant with NO complements this phenotype. The bacterial pathogen-associated molecular pattern elicitor lipopolysaccharide activates a CNGC Ca(2+) current, which may be linked to NO generation due to buildup of cytosolic Ca(2+)/calmodulin.

The host-pathogen interaction between wheat and yellow rust induces temporally coordinated waves of gene expression.

PubMed

Dobon, Albor; Bunting, Daniel C E; Cabrera-Quio, Luis Enrique; Uauy, Cristobal; Saunders, Diane G O

2016-05-20

Understanding how plants and pathogens modulate gene expression during the host-pathogen interaction is key to uncovering the molecular mechanisms that regulate disease progression. Recent advances in sequencing technologies have provided new opportunities to decode the complexity of such interactions. In this study, we used an RNA-based sequencing approach (RNA-seq) to assess the global expression profiles of the wheat yellow rust pathogen Puccinia striiformis f. sp. tritici (PST) and its host during infection. We performed a detailed RNA-seq time-course for a susceptible and a resistant wheat host infected with PST. This study (i) defined the global gene expression profiles for PST and its wheat host, (ii) substantially improved the gene models for PST, (iii) evaluated the utility of several programmes for quantification of global gene expression for PST and wheat, and (iv) identified clusters of differentially expressed genes in the host and pathogen. By focusing on components of the defence response in susceptible and resistant hosts, we were able to visualise the effect of PST infection on the expression of various defence components and host immune receptors. Our data showed sequential, temporally coordinated activation and suppression of expression of a suite of immune-response regulators that varied between compatible and incompatible interactions. These findings provide the framework for a better understanding of how PST causes disease and support the idea that PST can suppress the expression of defence components in wheat to successfully colonize a susceptible host.

Food for contagion: synthesis and future directions for studying host-parasite responses to resource shifts in anthropogenic environments.

PubMed

Altizer, Sonia; Becker, Daniel J; Epstein, Jonathan H; Forbes, Kristian M; Gillespie, Thomas R; Hall, Richard J; Hawley, Dana M; Hernandez, Sonia M; Martin, Lynn B; Plowright, Raina K; Satterfield, Dara A; Streicker, Daniel G

2018-05-05

Human-provided resource subsidies for wildlife are diverse, common and have profound consequences for wildlife-pathogen interactions, as demonstrated by papers in this themed issue spanning empirical, theoretical and management perspectives from a range of study systems. Contributions cut across scales of organization, from the within-host dynamics of immune function, to population-level impacts on parasite transmission, to landscape- and regional-scale patterns of infection. In this concluding paper, we identify common threads and key findings from author contributions, including the consequences of resource subsidies for (i) host immunity; (ii) animal aggregation and contact rates; (iii) host movement and landscape-level infection patterns; and (iv) interspecific contacts and cross-species transmission. Exciting avenues for future work include studies that integrate mechanistic modelling and empirical approaches to better explore cross-scale processes, and experimental manipulations of food resources to quantify host and pathogen responses. Work is also needed to examine evolutionary responses to provisioning, and ask how diet-altered changes to the host microbiome influence infection processes. Given the massive public health and conservation implications of anthropogenic resource shifts, we end by underscoring the need for practical recommendations to manage supplemental feeding practices, limit human-wildlife conflicts over shared food resources and reduce cross-species transmission risks, including to humans.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'. © 2018 The Author(s).

Protein-protein interactions in the RPS4/RRS1 immune receptor complex

PubMed Central

Sarris, Panagiotis F.

2017-01-01

Plant NLR (Nucleotide-binding domain and Leucine-rich Repeat) immune receptor proteins are encoded by Resistance (R) genes and confer specific resistance to pathogen races that carry the corresponding recognized effectors. Some NLR proteins function in pairs, forming receptor complexes for the perception of specific effectors. We show here that the Arabidopsis RPS4 and RRS1 NLR proteins are both required to make an authentic immune complex. Over-expression of RPS4 in tobacco or in Arabidopsis results in constitutive defense activation; this phenotype is suppressed in the presence of RRS1. RRS1 protein co-immunoprecipitates (co-IPs) with itself in the presence or absence of RPS4, but in contrast, RPS4 does not associate with itself in the absence of RRS1. In the presence of RRS1, RPS4 associates with defense signaling regulator EDS1 solely in the nucleus, in contrast to the extra-nuclear location found in the absence of RRS1. The AvrRps4 effector does not disrupt RPS4-EDS1 association in the presence of RRS1. In the absence of RRS1, AvrRps4 interacts with EDS1, forming nucleocytoplasmic aggregates, the formation of which is disturbed by the co-expression of PAD4 but not by SAG101. These data indicate that the study of an immune receptor protein complex in the absence of all components can result in misleading inferences, and reveals an NLR complex that dynamically interacts with the immune regulators EDS1/PAD4 or EDS1/SAG101, and with effectors, during the process by which effector recognition is converted to defense activation. PMID:28475615

The role of nitric oxide in the interaction of Arabidopsis thaliana with the biotrophic fungi, Golovinomyces orontii and Erysiphe pisi.

PubMed

Schlicht, Markus; Kombrink, Erich

2013-01-01

Powdery mildews are a diverse group of pathogenic fungi that can infect a large number of plant species, including many economically important crops. However, basic and applied research on these devastating diseases has been hampered by the obligate biotrophic lifestyle of the pathogens, which require living host cells for growth and reproduction, and lacking genetic and molecular tools for important host plants. The establishment of Arabidopsis thaliana as a host of different powdery mildew species allowed pursuing new strategies to study the molecular mechanisms governing these complex plant-pathogen interactions. Nitric oxide (NO) has emerged as an important signaling molecule in plants, which is produced upon infection and involved in activation of plant immune responses. However, the source and pathway of NO production and its precise function in the regulatory network of reactions leading to resistance is still unknown. We studied the response of Arabidopsis thaliana to infection with the adapted powdery mildew, Golovinomyces orontii (compatible interaction) and the non-adapted, Erysiphe pisi (incompatible interaction). We observed that NO accumulated rapidly and transiently at infection sites and we established a correlation between the resistance phenotype and the amount and timing of NO production. Arabidopsis mutants with defective immune response accumulated lower NO levels compared to wild type. Conversely, increased NO levels, generated by treatment with chemicals or expression of a NO-synthesizing enzyme, resulted in enhanced resistance, but only sustained NO production prevented excessive leaf colonization by the fungus, which was not achieved by a short NO burst although this reduced the initial penetration success. By contrast, lowered NO levels did not impair the ultimate resistance phenotype. Although our results suggest a function of NO in mediating plant immune responses, a direct impact on pathogen growth and development cannot be excluded.

Rice Exo70 interacts with a fungal effector, AVR-Pii, and is required for AVR-Pii-triggered immunity.

PubMed

Fujisaki, Koki; Abe, Yoshiko; Ito, Akiko; Saitoh, Hiromasa; Yoshida, Kentaro; Kanzaki, Hiroyuki; Kanzaki, Eiko; Utsushi, Hiroe; Yamashita, Tetsuro; Kamoun, Sophien; Terauchi, Ryohei

2015-09-01

Vesicle trafficking including the exocytosis pathway is intimately associated with host immunity against pathogens. However, we still have insufficient knowledge about how it contributes to immunity, and how pathogen factors affect it. In this study, we explore host factors that interact with the Magnaporthe oryzae effector AVR-Pii. Gel filtration chromatography and co-immunoprecipitation assays identified a 150 kDa complex of proteins in the soluble fraction comprising AVR-Pii and OsExo70-F2 and OsExo70-F3, two rice Exo70 proteins presumably involved in exocytosis. Simultaneous knockdown of OsExo70-F2 and F3 totally abrogated Pii immune receptor-dependent resistance, but had no effect on Pia- and Pik-dependent resistance. Knockdown levels of OsExo70-F3 but not OsExo70-F2 correlated with reduction of Pii function, suggesting that OsExo70-F3 is specifically involved in Pii-dependent resistance. Under our current experimental conditions, over-expression of AVR-Pii or knockdown of OsExo70-F2 and -F3 genes in rice did not affect the virulence of compatible isolates of M. oryzae. AVR-Pii interaction with OsExo70-F3 appears to play a crucial role in immunity triggered by Pii, suggesting a role for OsExo70 as a decoy or helper in Pii/AVR-Pii interactions. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens.

PubMed

Cabinian, Allison; Sinsimer, Daniel; Tang, May; Jang, Youngsoon; Choi, Bongkum; Laouar, Yasmina; Laouar, Amale

2018-05-01

Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field. We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is. Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFP tg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium . SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC) TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death. SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pathogen effectors target Arabidopsis EDS1 and alter its interactions with immune regulators.

PubMed

Bhattacharjee, Saikat; Halane, Morgan K; Kim, Sang Hee; Gassmann, Walter

2011-12-09

Plant resistance proteins detect the presence of specific pathogen effectors and initiate effector-triggered immunity. Few immune regulators downstream of resistance proteins have been identified, none of which are known virulence targets of effectors. We show that Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1), a positive regulator of basal resistance and of effector-triggered immunity specifically mediated by Toll-interleukin-1 receptor-nucleotide binding-leucine-rich repeat (TIR-NB-LRR) resistance proteins, forms protein complexes with the TIR-NB-LRR disease resistance proteins RPS4 and RPS6 and with the negative immune regulator SRFR1 at a cytoplasmic membrane. Further, the cognate bacterial effectors AvrRps4 and HopA1 disrupt these EDS1 complexes. Tight association of EDS1 with TIR-NB-LRR-mediated immunity may therefore derive mainly from being guarded by TIR-NB-LRR proteins, and activation of this branch of effector-triggered immunity may directly connect to the basal resistance signaling pathway via EDS1.

Targeting the complex interactions between microbiota, host epithelial and immune cells in inflammatory bowel disease.

PubMed

Hirata, Yoshihiro; Ihara, Sozaburo; Koike, Kazuhiko

2016-11-01

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder that includes two distinct disease categories: ulcerative colitis and Crohn's disease. Epidemiological, genetic, and experimental studies have revealed many important aspects of IBD. Genetic susceptibility, inappropriate immune responses, environmental changes, and intestinal microbiota are all associated with the development of IBD. However, the exact mechanisms of the disease and the interactions among these pathogenic factors are largely unknown. Here we introduce recent findings from experimental colitis models that investigated the interactions between host genetic susceptibility and gut microbiota. In addition, we discuss new strategies for the treatment of IBD, focusing on the complex interactions between microbiota and host epithelial and immune cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus.

PubMed

Hellmann, Anna-Maria; Lother, Jasmin; Wurster, Sebastian; Lutz, Manfred B; Schmitt, Anna Lena; Morton, Charles Oliver; Eyrich, Matthias; Czakai, Kristin; Einsele, Hermann; Loeffler, Juergen

2017-01-01

Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus . However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus . For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus . Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host-pathogen interaction studies.

Human and Murine Innate Immune Cell Populations Display Common and Distinct Response Patterns during Their In Vitro Interaction with the Pathogenic Mold Aspergillus fumigatus

PubMed Central

Hellmann, Anna-Maria; Lother, Jasmin; Wurster, Sebastian; Lutz, Manfred B.; Schmitt, Anna Lena; Morton, Charles Oliver; Eyrich, Matthias; Czakai, Kristin; Einsele, Hermann; Loeffler, Juergen

2017-01-01

Aspergillus fumigatus is the main cause of invasive fungal infections occurring almost exclusively in immunocompromised patients. An improved understanding of the initial innate immune response is key to the development of better diagnostic tools and new treatment options. Mice are commonly used to study immune defense mechanisms during the infection of the mammalian host with A. fumigatus. However, little is known about functional differences between the human and murine immune response against this fungal pathogen. Thus, we performed a comparative functional analysis of human and murine dendritic cells (DCs), macrophages, and polymorphonuclear cells (PMNs) using standardized and reproducible working conditions, laboratory protocols, and readout assays. A. fumigatus did not provoke identical responses in murine and human immune cells but rather initiated relatively specific responses. While human DCs showed a significantly stronger upregulation of their maturation markers and major histocompatibility complex molecules and phagocytosed A. fumigatus more efficiently compared to their murine counterparts, murine PMNs and macrophages exhibited a significantly stronger release of reactive oxygen species after exposure to A. fumigatus. For all studied cell types, human and murine samples differed in their cytokine response to conidia or germ tubes of A. fumigatus. Furthermore, Dectin-1 showed inverse expression patterns on human and murine DCs after fungal stimulation. These specific differences should be carefully considered and highlight potential limitations in the transferability of murine host–pathogen interaction studies. PMID:29270175

Characterization of mediators of microbial virulence and innate immunity using the Caenorhabditis elegans host-pathogen model.

PubMed

Alegado, Rosanna A; Campbell, Marianne C; Chen, Will C; Slutz, Sandra S; Tan, Man-Wah

2003-07-01

The soil-borne nematode, Caenorhabditis elegans, is emerging as a versatile model in which to study host-pathogen interactions. The worm model has shown to be particularly effective in elucidating both microbial and animal genes involved in toxin-mediated killing. In addition, recent work on worm infection by a variety of bacterial pathogens has shown that a number of virulence regulatory genes mediate worm susceptibility. Many of these regulatory genes, including the PhoP/Q two-component regulators in Salmonella and LasR in Pseudomonas aeruginosa, have also been implicated in mammalian models suggesting that findings in the worm model will be relevant to other systems. In keeping with this concept, experiments aimed at identifying host innate immunity genes have also implicated pathways that have been suggested to play a role in plants and animals, such as the p38 MAP kinase pathway. Despite rapid forward progress using this model, much work remains to be done including the design of more sensitive methods to find effector molecules and further characterization of the exact interaction between invading pathogens and C. elegans' cellular components.

Host-pathogen interplay in the respiratory environment of Cystic Fibrosis

PubMed Central

Hurley, Bryan P.; Bragonzi, Alessandra

2015-01-01

Significant advances have been made in the understanding of disease progression in cystic fibrosis (CF), revealing a complex interplay between host and pathogenic organisms. The diverse CF microbiota within the airway activates an aberrant immune response that is ineffective in clearing infection. An appreciation of how the CF host immune system interacts with these organisms is crucial to understanding the pathogenesis of CF pulmonary disease. Here we discuss the microbial complexity present in the lungs of individuals with CF, review emerging concepts of innate and adaptive immune responses to pathogens that chronically inhabit the CF lung, and discuss therapies that target the aberrant inflammatory response that characterizes CF. A greater understanding of the underlying mechanisms will shed light on pathogenesis and guide more targeted therapies in the future that serve to reduce infection, minimize lung pathology, and improve the quality of life for patients with CF. PMID:25800687

Group B Streptococcal Maternal Colonization and Neonatal Disease: Molecular Mechanisms and Preventative Approaches

PubMed Central

Patras, Kathryn A.; Nizet, Victor

2018-01-01

Group B Streptococcus (GBS) colonizes the gastrointestinal and vaginal epithelium of a significant percentage of healthy women, with potential for ascending intrauterine infection or transmission during parturition, creating a risk of serious disease in the vulnerable newborn. This review highlights new insights on the bacterial virulence determinants, host immune responses, and microbiome interactions that underpin GBS vaginal colonization, the proximal step in newborn infectious disease pathogenesis. From the pathogen perspective, the function GBS adhesins and biofilms, β-hemolysin/cytolysin toxin, immune resistance factors, sialic acid mimicry, and two-component transcriptional regulatory systems are reviewed. From the host standpoint, pathogen recognition, cytokine responses, and the vaginal mucosal and placental immunity to the pathogen are detailed. Finally, the rationale, efficacy, and potential unintended consequences of current universal recommended intrapartum antibiotic prophylaxis are considered, with updates on new developments toward a GBS vaccine or alternative approaches to reducing vaginal colonization. PMID:29520354

Inactivation of conserved genes induces microbial aversion, drug detoxification, and innate immunity in C.elegans

PubMed Central

Melo, Justine A.; Ruvkun, Gary

2012-01-01

Summary The nematode C. elegans consumes benign bacteria such as E. coli and is repelled by pathogens and toxins. Here we show that RNAi and toxin-mediated disruption of core cellular activities, including translation, respiration, and protein turnover, stimulates behavioral avoidance of attractive E. coli. RNAi of such essential processes also induces expression of detoxification and innate immune response genes in the absence of toxins or pathogens. Disruption of core processes in non-neuronal tissues can stimulate aversion behavior, revealing a neuroendocrine axis of control. Microbial avoidance requires serotonergic and Jnk kinase signaling. We propose that surveillance pathways oversee critical cellular activities to detect pathogens, many of which deploy toxins and virulence factors to disrupt these same host pathways. Variation in cellular surveillance and endocrine pathways controlling behavior, detoxification and immunity selected by past toxin or microbial interactions could underlie aberrant responses to foods, medicines, and microbes. PMID:22500807

Bifidobacterium breve UCC2003 surface exopolysaccharide production is a beneficial trait mediating commensal-host interaction through immune modulation and pathogen protection.

PubMed

Fanning, Saranna; Hall, Lindsay J; van Sinderen, Douwe

2012-01-01

Bifidobacteria constitute a substantial proportion of the human gut microbiota. There are currently many bifidobacterial strains with claimed probiotic attributes. The mechanism through which these strains reside within their host and exert benefits to the host is far from fully understood. We have shown in the case of Bifidobacterium breve UCC2003 that a cell surface exopolysaccharide (EPS) plays a role in in vivo persistence. Biosynthesis of two possible EPSs is controlled by a bidirectional gene cluster which guides alternate EPS synthesis by means of a reorienting promoter. The presence of EPS impacts on host immune response: the wild type, EPS-positive B. breve UCC2003 efficiently evades the adaptive B-cell host response, while its isogenic, EPS-deficient equivalent elicits a strong adaptive immune response. Functionally, EPS positive strains were more resilient to presence of acid and bile and were responsible for reduced colonization levels of Citrobacter rodentium, a gut pathogen. In conclusion, we have found that EPS is important in host interactions and pathogen protection, the latter indicative of a probiotic ability for the EPS of B. breve UCC2003.

Insect antiviral innate immunity: pathways, effectors, and connections.

PubMed

Kingsolver, Megan B; Huang, Zhijing; Hardy, Richard W

2013-12-13

Insects are infected by a wide array of viruses some of which are insect restricted and pathogenic, and some of which are transmitted by biting insects to vertebrates. The medical and economic importance of these viruses heightens the need to understand the interaction between the infecting pathogen and the insect immune system in order to develop transmission interventions. The interaction of the virus with the insect host innate immune system plays a critical role in the outcome of infection. The major mechanism of antiviral defense is the small, interfering RNA pathway that responds through the detection of virus-derived double-stranded RNA to suppress virus replication. However, other innate antimicrobial pathways such as Imd, Toll, and Jak-STAT and the autophagy pathway have also been shown to play important roles in antiviral immunity. In this review, we provide an overview of the current understanding of the main insect antiviral pathways and examine recent findings that further our understanding of the roles of these pathways in facilitating a systemic and specific response to infecting viruses. © 2013.

Two-Partner Secretion: Combining Efficiency and Simplicity in the Secretion of Large Proteins for Bacteria-Host and Bacteria-Bacteria Interactions

PubMed Central

Guérin, Jeremy; Bigot, Sarah; Schneider, Robert; Buchanan, Susan K.; Jacob-Dubuisson, Françoise

2017-01-01

Initially identified in pathogenic Gram-negative bacteria, the two-partner secretion (TPS) pathway, also known as Type Vb secretion, mediates the translocation across the outer membrane of large effector proteins involved in interactions between these pathogens and their hosts. More recently, distinct TPS systems have been shown to secrete toxic effector domains that participate in inter-bacterial competition or cooperation. The effects of these systems are based on kin vs. non-kin molecular recognition mediated by specific immunity proteins. With these new toxin-antitoxin systems, the range of TPS effector functions has thus been extended from cytolysis, adhesion, and iron acquisition, to genome maintenance, inter-bacterial killing and inter-bacterial signaling. Basically, a TPS system is made up of two proteins, the secreted TpsA effector protein and its TpsB partner transporter, with possible additional factors such as immunity proteins for protection against cognate toxic effectors. Structural studies have indicated that TpsA proteins mainly form elongated β helices that may be followed by specific functional domains. TpsB proteins belong to the Omp85 superfamily. Open questions remain on the mechanism of protein secretion in the absence of ATP or an electrochemical gradient across the outer membrane. The remarkable dynamics of the TpsB transporters and the progressive folding of their TpsA partners at the bacterial surface in the course of translocation are thought to be key elements driving the secretion process. PMID:28536673

Ocean acidification and host-pathogen interactions: blue mussels, Mytilus edulis, encountering Vibrio tubiashii.

PubMed

Asplund, Maria E; Baden, Susanne P; Russ, Sarah; Ellis, Robert P; Gong, Ningping; Hernroth, Bodil E

2014-04-01

Ocean acidification (OA) can shift the ecological balance between interacting organisms. In this study, we have used a model system to illustrate the interaction between a calcifying host organism, the blue mussel Mytilus edulis and a common bivalve bacterial pathogen, Vibrio tubiashii, with organisms being exposed to a level of acidification projected to occur by the end of the 21st century. OA exposures of the mussels were carried out in relative long-term (4 months) and short-term (4 days) experiments. We found no effect of OA on the culturability of V. tubiashii, in broth or in seawater. OA inhibited mussel shell growth and impaired crystalline shell structures but did not appear to affect mussel immune parameters (i.e haemocyte counts and phagocytotic capacity). Despite no evident impact on host immunity or growth and virulence of the pathogen, V. tubiashii was clearly more successful in infecting mussels exposed to long-term OA compared to those maintained under ambient conditions. Moreover, OA exposed V. tubiashii increased their viability when exposed to haemocytes of OA-treated mussel. Our findings suggest that even though host organisms may have the capacity to cope with periods of OA, these conditions may alter the outcome of host-pathogen interactions, favouring the success of the latter. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Dynamic gene expression analysis in a H1N1 influenza virus mouse pneumonia model.

PubMed

Bao, Yanyan; Gao, Yingjie; Shi, Yujing; Cui, Xiaolan

2017-06-01

H1N1, a major pathogenic subtype of influenza A virus, causes a respiratory infection in humans and livestock that can range from a mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Understanding the dynamic changes in the genome and the related functional changes induced by H1N1 influenza virus infection is essential to elucidating the pathogenesis of this virus and thereby determining strategies to prevent future outbreaks. In this study, we filtered the significantly expressed genes in mouse pneumonia using mRNA microarray analysis. Using STC analysis, seven significant gene clusters were revealed, and using STC-GO analysis, we explored the significant functions of these seven gene clusters. The results revealed GOs related to H1N1 virus-induced inflammatory and immune functions, including innate immune response, inflammatory response, specific immune response, and cellular response to interferon-beta. Furthermore, the dynamic regulation relationships of the key genes in mouse pneumonia were revealed by dynamic gene network analysis, and the most important genes were filtered, including Dhx58, Cxcl10, Cxcl11, Zbp1, Ifit1, Ifih1, Trim25, Mx2, Oas2, Cd274, Irgm1, and Irf7. These results suggested that during mouse pneumonia, changes in the expression of gene clusters and the complex interactions among genes lead to significant changes in function. Dynamic gene expression analysis revealed key genes that performed important functions. These results are a prelude to advancements in mouse H1N1 influenza virus infection biology, as well as the use of mice as a model organism for human H1N1 influenza virus infection studies.

Plant response to biotic stress: Is there a common epigenetic response during plant-pathogenic and symbiotic interactions?

PubMed

Zogli, Prince; Libault, Marc

2017-10-01

Plants constantly interact with pathogenic and symbiotic microorganisms. Recent studies have revealed several regulatory mechanisms controlling these interactions. Among them, the plant defense system is activated not only in response to pathogenic, but also in response to symbiotic microbes. Interestingly, shortly after symbiotic microbial recognition, the plant defense system is suppressed to promote plant infection by symbionts. Research studies have demonstrated the influence of the plant epigenome in modulating both pathogenic and symbiotic plant-microbe interactions, thereby influencing plant survival, adaptation and evolution of the plant response to microbial infections. It is however unclear if plant pathogenic and symbiotic responses share similar epigenomic profiles or if epigenomic changes differentially regulate plant-microbe symbiosis and pathogenesis. In this mini-review, we provide an update of the current knowledge of epigenomic control on plant immune responses and symbiosis, with a special attention being paid to knowledge gap and potential strategies to fill-in the missing links. Copyright © 2017 Elsevier B.V. All rights reserved.

Epigenetic control of plant immunity.

PubMed

Alvarez, María E; Nota, Florencia; Cambiagno, Damián A

2010-07-01

In eukaryotic genomes, gene expression and DNA recombination are affected by structural chromatin traits. Chromatin structure is shaped by the activity of enzymes that either introduce covalent modifications in DNA and histone proteins or use energy from ATP to disrupt histone-DNA interactions. The genomic 'marks' that are generated by covalent modifications of histones and DNA, or by the deposition of histone variants, are susceptible to being altered in response to stress. Recent evidence has suggested that proteins generating these epigenetic marks play crucial roles in the defence against pathogens. Histone deacetylases are involved in the activation of jasmonic acid- and ethylene-sensitive defence mechanisms. ATP-dependent chromatin remodellers mediate the constitutive repression of the salicylic acid-dependent pathway, whereas histone methylation at the WRKY70 gene promoter affects the activation of this pathway. Interestingly, bacterial-infected tissues show a net reduction in DNA methylation, which may affect the disease resistance genes responsible for the surveillance against pathogens. As some epigenetic marks can be erased or maintained and transmitted to offspring, epigenetic mechanisms may provide plasticity for the dynamic control of emerging pathogens without the generation of genomic lesions.

Effects of immunostimulation on social behavior, chemical communication and genome-wide gene expression in honey bee workers (Apis mellifera)

PubMed Central

2012-01-01

Background Social insects, such as honey bees, use molecular, physiological and behavioral responses to combat pathogens and parasites. The honey bee genome contains all of the canonical insect immune response pathways, and several studies have demonstrated that pathogens can activate expression of immune effectors. Honey bees also use behavioral responses, termed social immunity, to collectively defend their hives from pathogens and parasites. These responses include hygienic behavior (where workers remove diseased brood) and allo-grooming (where workers remove ectoparasites from nestmates). We have previously demonstrated that immunostimulation causes changes in the cuticular hydrocarbon profiles of workers, which results in altered worker-worker social interactions. Thus, cuticular hydrocarbons may enable workers to identify sick nestmates, and adjust their behavior in response. Here, we test the specificity of behavioral, chemical and genomic responses to immunostimulation by challenging workers with a panel of different immune stimulants (saline, Sephadex beads and Gram-negative bacteria E. coli). Results While only bacteria-injected bees elicited altered behavioral responses from healthy nestmates compared to controls, all treatments resulted in significant changes in cuticular hydrocarbon profiles. Immunostimulation caused significant changes in expression of hundreds of genes, the majority of which have not been identified as members of the canonical immune response pathways. Furthermore, several new candidate genes that may play a role in cuticular hydrocarbon biosynthesis were identified. Effects of immune challenge expression of several genes involved in immune response, cuticular hydrocarbon biosynthesis, and the Notch signaling pathway were confirmed using quantitative real-time PCR. Finally, we identified common genes regulated by pathogen challenge in honey bees and other insects. Conclusions These results demonstrate that honey bee genomic responses to immunostimulation are substantially broader than the previously identified canonical immune response pathways, and may mediate the behavioral changes associated with social immunity by orchestrating changes in chemical signaling. These studies lay the groundwork for future research into the genomic responses of honey bees to native honey bee parasites and pathogens. PMID:23072398

Effects of immunostimulation on social behavior, chemical communication and genome-wide gene expression in honey bee workers (Apis mellifera).

PubMed

Richard, Freddie-Jeanne; Holt, Holly L; Grozinger, Christina M

2012-10-16

Social insects, such as honey bees, use molecular, physiological and behavioral responses to combat pathogens and parasites. The honey bee genome contains all of the canonical insect immune response pathways, and several studies have demonstrated that pathogens can activate expression of immune effectors. Honey bees also use behavioral responses, termed social immunity, to collectively defend their hives from pathogens and parasites. These responses include hygienic behavior (where workers remove diseased brood) and allo-grooming (where workers remove ectoparasites from nestmates). We have previously demonstrated that immunostimulation causes changes in the cuticular hydrocarbon profiles of workers, which results in altered worker-worker social interactions. Thus, cuticular hydrocarbons may enable workers to identify sick nestmates, and adjust their behavior in response. Here, we test the specificity of behavioral, chemical and genomic responses to immunostimulation by challenging workers with a panel of different immune stimulants (saline, Sephadex beads and Gram-negative bacteria E. coli). While only bacteria-injected bees elicited altered behavioral responses from healthy nestmates compared to controls, all treatments resulted in significant changes in cuticular hydrocarbon profiles. Immunostimulation caused significant changes in expression of hundreds of genes, the majority of which have not been identified as members of the canonical immune response pathways. Furthermore, several new candidate genes that may play a role in cuticular hydrocarbon biosynthesis were identified. Effects of immune challenge expression of several genes involved in immune response, cuticular hydrocarbon biosynthesis, and the Notch signaling pathway were confirmed using quantitative real-time PCR. Finally, we identified common genes regulated by pathogen challenge in honey bees and other insects. These results demonstrate that honey bee genomic responses to immunostimulation are substantially broader than the previously identified canonical immune response pathways, and may mediate the behavioral changes associated with social immunity by orchestrating changes in chemical signaling. These studies lay the groundwork for future research into the genomic responses of honey bees to native honey bee parasites and pathogens.

Predators indirectly control vector-borne disease: linking predator-prey and host-pathogen models.

PubMed

Moore, Sean M; Borer, Elizabeth T; Hosseini, Parviez R

2010-01-06

Pathogens transmitted by arthropod vectors are common in human populations, agricultural systems and natural communities. Transmission of these vector-borne pathogens depends on the population dynamics of the vector species as well as its interactions with other species within the community. In particular, predation may be sufficient to control pathogen prevalence indirectly via the vector. To examine the indirect effect of predators on vectored-pathogen dynamics, we developed a theoretical model that integrates predator-prey and host-pathogen theory. We used this model to determine whether predation can prevent pathogen persistence or alter the stability of host-pathogen dynamics. We found that, in the absence of predation, pathogen prevalence in the host increases with vector fecundity, whereas predation on the vector causes pathogen prevalence to decline, or even become extinct, with increasing vector fecundity. We also found that predation on a vector may drastically slow the initial spread of a pathogen. The predator can increase host abundance indirectly by reducing or eliminating infection in the host population. These results highlight the importance of studying interactions that, within the greater community, may alter our predictions when studying disease dynamics. From an applied perspective, these results also suggest situations where an introduced predator or the natural enemies of a vector may slow the rate of spread of an emerging vector-borne pathogen.

Trans-Kingdom RNA Silencing in Plant-Fungal Pathogen Interactions.

PubMed

Hua, Chenlei; Zhao, Jian-Hua; Guo, Hui-Shan

2018-02-05

Fungal pathogens represent a major group of plant invaders that are the causative agents of many notorious plant diseases. Large quantities of RNAs, especially small RNAs involved in gene silencing, have been found to transmit bidirectionally between fungal pathogens and their hosts. Although host-induced gene silencing (HIGS) technology has been developed and applied to protect crops from fungal infections, the mechanisms of RNA transmission, especially small RNAs regulating trans-kingdom RNA silencing in plant immunity, are largely unknown. In this review, we summarize and discuss recent important findings regarding trans-kingdom sRNAs and RNA silencing in plant-fungal pathogen interactions compared with the well-known RNAi mechanisms in plants and fungi. We focus on the interactions between plant and fungal pathogens with broad hosts, represented by the vascular pathogen Verticillium dahliae and non-vascular pathogen Botrytis cinerea, and discuss the known instances of natural RNAi transmission between fungal pathogens and host plants. Given that HIGS has been developed and recently applied in controlling Verticillium wilt diseases, we propose an ideal research system exploiting plant vasculature-Verticillium interaction to further study trans-kingdom RNA silencing. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Combining ANOVA-PCA with POCHEMON to analyse micro-organism development in a polymicrobial environment.

PubMed

Geurts, Brigitte P; Neerincx, Anne H; Bertrand, Samuel; Leemans, Manja A A P; Postma, Geert J; Wolfender, Jean-Luc; Cristescu, Simona M; Buydens, Lutgarde M C; Jansen, Jeroen J

2017-04-22

Revealing the biochemistry associated to micro-organismal interspecies interactions is highly relevant for many purposes. Each pathogen has a characteristic metabolic fingerprint that allows identification based on their unique multivariate biochemistry. When pathogen species come into mutual contact, their co-culture will display a chemistry that may be attributed both to mixing of the characteristic chemistries of the mono-cultures and to competition between the pathogens. Therefore, investigating pathogen development in a polymicrobial environment requires dedicated chemometric methods to untangle and focus upon these sources of variation. The multivariate data analysis method Projected Orthogonalised Chemical Encounter Monitoring (POCHEMON) is dedicated to highlight metabolites characteristic for the interaction of two micro-organisms in co-culture. However, this approach is currently limited to a single time-point, while development of polymicrobial interactions may be highly dynamic. A well-known multivariate implementation of Analysis of Variance (ANOVA) uses Principal Component Analysis (ANOVA-PCA). This allows the overall dynamics to be separated from the pathogen-specific chemistry to analyse the contributions of both aspects separately. For this reason, we propose to integrate ANOVA-PCA with the POCHEMON approach to disentangle the pathogen dynamics and the specific biochemistry in interspecies interactions. Two complementary case studies show great potential for both liquid and gas chromatography - mass spectrometry to reveal novel information on chemistry specific to interspecies interaction during pathogen development. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Interaction of the Human Contact System with Pathogens-An Update.

PubMed

Oehmcke-Hecht, Sonja; Köhler, Juliane

2018-01-01

The name human contact system is related to its mode of action, as "contact" with artificial negatively charged surfaces triggers its activation. Today, it is generally believed that the contact system is an inflammatory response mechanism not only against artificial material but also against misfolded proteins and foreign organisms. Upon activation, the contact system is involved in at least two distinct (patho)physiologic processes: i . the trigger of the intrinsic coagulation via factor XI and ii . the cleavage of high molecular weight kininogen with release of bradykinin and antimicrobial peptides (AMPs). Bradykinin is involved in the regulation of inflammatory processes, vascular permeability, and blood pressure. Due to the release of AMPs, the contact system is regarded as a branch of the innate immune defense against microorganisms. There is an increasing list of pathogens that interact with contact factors, in addition to bacteria also fungi and viruses bind and activate the system. In spite of that, pathogens have developed their own mechanisms to activate the contact system, resulting in manipulation of this host immune response. In this up-to-date review, we summarize present research on the interaction of pathogens with the human contact system, focusing particularly on bacterial and viral mechanisms that trigger inflammation via contact system activation.

Pathogen-Sensing and Regulatory T Cells: Integrated Regulators of Immune Responses

PubMed Central

Grossman, Zvi; Paul, William E.

2014-01-01

We present the concept that pathogen-sensing and Tregs mutually regulate immune responses to conventional and tumor antigens through countervailing effects on dendritic cells. Normally, conventional CD4 T cells recognizing their cognate antigen-presented by a dendritic cell will respond only if the dendritic cell also receives a signal through its pathogen-sensing/ danger / adjuvant recognition systems (the pathogen-sensing triad). However, if Tregs capable of interacting with the same DC are absent, dendritic cells are competent to present antigens, both foreign and self, even without the stimulation provided by the pathogen-sensing triad. Tregs recognizing an antigen presented by the DC that is also presenting antigen to a conventional CD4 T cell will prevent such responses but a signal delivered by a member of the pathogen-sensing traid will overcome the Tregs’inhibitory action and will allow responses to go forward. These considerations take on special meaning for responses to “weak antigens” such as many of the antigens displayed by spontaneous human tumors. PMID:24894087

Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs

PubMed Central

Munguia, Jason; Nizet, Victor

2017-01-01

The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic therapy in the richer context of the host-pathogen interaction is required for innovative solutions. By defining specific virulence factors, the essence of a pathogen, and pharmacologically neutralizing their activities, one can block disease progression and sensitize microbes to immune clearance. Likewise, host-directed strategies to boost phagocyte bactericidal activity, enhance leukocyte recruitment, or reverse pathogen-induced immunosuppression seek to replicate the success of cancer immunotherapy in the field of infectious diseases. The answer to the threat of multidrug-resistant pathogens lies “outside-the-box” of current antibiotic paradigms. PMID:28283200

Mechanisms of action of Coxiella burnetii effectors inferred from host-pathogen protein interactions.

PubMed

Wallqvist, Anders; Wang, Hao; Zavaljevski, Nela; Memišević, Vesna; Kwon, Keehwan; Pieper, Rembert; Rajagopala, Seesandra V; Reifman, Jaques

2017-01-01

Coxiella burnetii is an obligate Gram-negative intracellular pathogen and the etiological agent of Q fever. Successful infection requires a functional Type IV secretion system, which translocates more than 100 effector proteins into the host cytosol to establish the infection, restructure the intracellular host environment, and create a parasitophorous vacuole where the replicating bacteria reside. We used yeast two-hybrid (Y2H) screening of 33 selected C. burnetii effectors against whole genome human and murine proteome libraries to generate a map of potential host-pathogen protein-protein interactions (PPIs). We detected 273 unique interactions between 20 pathogen and 247 human proteins, and 157 between 17 pathogen and 137 murine proteins. We used orthology to combine the data and create a single host-pathogen interaction network containing 415 unique interactions between 25 C. burnetii and 363 human proteins. We further performed complementary pairwise Y2H testing of 43 out of 91 C. burnetii-human interactions involving five pathogen proteins. We used the combined data to 1) perform enrichment analyses of target host cellular processes and pathways, 2) examine effectors with known infection phenotypes, and 3) infer potential mechanisms of action for four effectors with uncharacterized functions. The host-pathogen interaction profiles supported known Coxiella phenotypes, such as adapting cell morphology through cytoskeletal re-arrangements, protein processing and trafficking, organelle generation, cholesterol processing, innate immune modulation, and interactions with the ubiquitin and proteasome pathways. The generated dataset of PPIs-the largest collection of unbiased Coxiella host-pathogen interactions to date-represents a rich source of information with respect to secreted pathogen effector proteins and their interactions with human host proteins.

Interactions between parasites and microbial communities in the human gut.

PubMed

Berrilli, Federica; Di Cave, David; Cavallero, Serena; D'Amelio, Stefano

2012-01-01

The interactions between intestinal microbiota, immune system, and pathogens describe the human gut as a complex ecosystem, where all components play a relevant role in modulating each other and in the maintenance of homeostasis. The balance among the gut microbiota and the human body appear to be crucial for health maintenance. Intestinal parasites, both protozoans and helminths, interact with the microbial community modifying the balance between host and commensal microbiota. On the other hand, gut microbiota represents a relevant factor that may strongly interfere with the pathophysiology of the infections. In addition to the function that gut commensal microbiota may have in the processes that determine the survival and the outcome of many parasitic infections, including the production of nutritive macromolecules, also probiotics can play an important role in reducing the pathogenicity of many parasites. On these bases, there is a growing interest in explaining the rationale on the possible interactions between the microbiota, immune response, inflammatory processes, and intestinal parasites.

Interactions between parasites and microbial communities in the human gut

PubMed Central

Berrilli, Federica; Di Cave, David; Cavallero, Serena; D'Amelio, Stefano

2012-01-01

The interactions between intestinal microbiota, immune system, and pathogens describe the human gut as a complex ecosystem, where all components play a relevant role in modulating each other and in the maintenance of homeostasis. The balance among the gut microbiota and the human body appear to be crucial for health maintenance. Intestinal parasites, both protozoans and helminths, interact with the microbial community modifying the balance between host and commensal microbiota. On the other hand, gut microbiota represents a relevant factor that may strongly interfere with the pathophysiology of the infections. In addition to the function that gut commensal microbiota may have in the processes that determine the survival and the outcome of many parasitic infections, including the production of nutritive macromolecules, also probiotics can play an important role in reducing the pathogenicity of many parasites. On these bases, there is a growing interest in explaining the rationale on the possible interactions between the microbiota, immune response, inflammatory processes, and intestinal parasites. PMID:23162802

RNA-protein interactions in plant disease: hackers at the dinner table.

PubMed

Spanu, Pietro D

2015-09-01

Plants are the source of most of our food, whether directly or as feed for the animals we eat. Our dinner table is a trophic level we share with the microbes that also feed on the primary photosynthetic producers. Microbes that enter into close interactions with plants need to evade or suppress detection and host immunity to access nutrients. They do this by deploying molecular tools - effectors - which target host processes. The mode of action of effector proteins in these events is varied and complex. Recent data from diverse systems indicate that RNA-interacting proteins and RNA itself are delivered by eukaryotic microbes, such as fungi and oomycetes, to host plants and contribute to the establishment of successful interactions. This is evidence that pathogenic microbes can interfere with the host software. We are beginning to see that pathogenic microbes are capable of hacking into the plants' immunity programs. © 2015 The Author. New Phytologist © 2015 New Phytologist Trust.

Production of cross-kingdom oxylipins by pathogenic fungi: An update on their role in development and pathogenicity.

PubMed

Fischer, Gregory J; Keller, Nancy P

2016-03-01

Oxylipins are a class of molecules derived from the incorporation of oxygen into polyunsaturated fatty acid substrates through the action of oxygenases. While extensively investigated in the context of mammalian immune responses, over the last decade it has become apparent that oxylipins are a common means of communication among and between plants, animals, and fungi to control development and alter host-microbe interactions. In fungi, some oxylipins are derived nonenzymatically while others are produced by lipoxygenases, cyclooxygenases, and monooxygenases with homology to plant and human enzymes. Recent investigations of numerous plant and human fungal pathogens have revealed oxylipins to be involved in the establishment and progression of disease. This review highlights oxylipin production by pathogenic fungi and their role in fungal development and pathogen/host interactions.

Effects of Mycotoxins on Mucosal Microbial Infection and Related Pathogenesis

PubMed Central

Park, Seong-Hwan; Kim, Dongwook; Kim, Juil; Moon, Yuseok

2015-01-01

Mycotoxins are fungal secondary metabolites detected in many agricultural commodities and water-damaged indoor environments. Susceptibility to mucosal infectious diseases is closely associated with immune dysfunction caused by mycotoxin exposure in humans and other animals. Many mycotoxins suppress immune function by decreasing the proliferation of activated lymphocytes, impairing phagocytic function of macrophages, and suppressing cytokine production, but some induce hypersensitive responses in different dose regimes. The present review describes various mycotoxin responses to infectious pathogens that trigger mucosa-associated diseases in the gastrointestinal and respiratory tracts of humans and other animals. In particular, it focuses on the effects of mycotoxin exposure on invasion, pathogen clearance, the production of cytokines and immunoglobulins, and the prognostic implications of interactions between infectious pathogens and mycotoxin exposure. PMID:26529017

How Can Elispot Add Information to Improve Knowledge on Tropical Diseases?

PubMed Central

Lima-Junior, Josué da Costa; Conceição-Silva, Fátima

2017-01-01

Elispot has been used as an important tool for detecting immune cells’ products and functions and has facilitated the understanding of host-pathogen interaction. Despite the incredible diversity of possibilities, two main approaches have been developed: the immunopathogenesis and diagnosis/prognosis of infectious diseases as well as cancer research. Much has been described on the topics of allergy, autoimmune diseases, and HIV-Aids, however, Elispot can also be applied to other infectious diseases, mainly leishmaniasis, malaria, some viruses, helminths and mycosis usually classified as tropical diseases. The comprehension of the function, concentration and diversity of the immune response in the infectious disease is pointed out as crucial to the development of infection or disease in humans and animals. In this review we will describe the knowledge already obtained using Elispot as a method for accessing the profile of immune response as well as the recent advances in information about host-pathogen interaction in order to better understand the clinical outcome of a group of tropical and neglected diseases. PMID:28961208

Ethylene-responsive element-binding factor 5, ERF5, is involved in chitin-induced innate immunity response.

PubMed

Son, Geon Hui; Wan, Jinrong; Kim, Hye Jin; Nguyen, Xuan Canh; Chung, Woo Sik; Hong, Jong Chan; Stacey, Gary

2012-01-01

Our recent work demonstrated that chitin treatment modulated the expression of 118 transcription factor (TF) genes in Arabidopsis. To investigate the potential roles of these TF in chitin signaling and plant defense, we initiated an interaction study among these TF proteins, as well as two chitin-activated mitogen-activated protein kinases (MPK3 and MPK6), using a yeast two-hybrid system. This study revealed interactions among the following proteins: three ethylene-responsive element-binding factors (ERF), five WRKY transcription factors, one scarecrow-like (SCL), and the two MPK, in addition to many other interactions, reflecting a complex TF interaction network. Most of these interactions were subsequently validated by other methods, such as pull-down and in planta bimolecular fluorescence complementation assays. The key node ERF5 was shown to interact with multiple proteins in the network, such as ERF6, ERF8, and SCL13, as well as MPK3 and MPK6. Interestingly, ERF5 appeared to negatively regulate chitin signaling and plant defense against the fungal pathogen Alternaria brassicicola and positively regulate salicylic acid signaling and plant defense against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Therefore, ERF5 may play an important role in plant innate immunity, likely through coordinating chitin and other defense pathways in plants in response to different pathogens.

Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen.

PubMed

Levin, Rebecca S; Hertz, Nicholas T; Burlingame, Alma L; Shokat, Kevan M; Mukherjee, Shaeri

2016-08-16

TGF-β activated kinase 1 (TAK1) is a critical signaling hub responsible for translating antigen binding signals to immune receptors for the activation of the AP-1 and NF-κB master transcriptional programs. Despite its importance, known substrates of TAK1 are limited to kinases of the MAPK and IKK families and include no direct effectors of biochemical processes. Here, we identify over 200 substrates of TAK1 using a chemical genetic kinase strategy. We validate phosphorylation of the dynamic switch II region of GTPase Rab1, a mediator of endoplasmic reticulum to Golgi vesicular transport, at T75 to be regulated by TAK1 in vivo. TAK1 preferentially phosphorylates the inactive (GDP-bound) state of Rab1. Phosphorylation of Rab1 disrupts interaction with GDP dissociation inhibitor 1 (GDI1), but not guanine exchange factor (GEF) or GTPase-activating protein (GAP) enzymes, and is exclusive to membrane-localized Rab1, suggesting phosphorylation may stimulate Rab1 membrane association. Furthermore, we found phosphorylation of Rab1 at T75 to be essential for Rab1 function. Previous studies established that the pathogen Legionella pneumophila is capable of hijacking Rab1 function through posttranslational modifications of the switch II region. Here, we present evidence that Rab1 is regulated by the host in a similar fashion, and that the innate immunity kinase TAK1 and Legionella effectors compete to regulate Rab1 by switch II modifications during infection.

Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics

PubMed Central

Jończyk-Matysiak, Ewa; Weber-Dąbrowska, Beata; Owczarek, Barbara; Międzybrodzki, Ryszard; Łusiak-Szelachowska, Marzanna; Łodej, Norbert; Górski, Andrzej

2017-01-01

Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes—contained in granules—that are potentially toxic proteins. Therefore, it is important to investigate the possible interactions between phages and immune cells and avoid any phage side effects on them. Recent progress in knowledge concerning the influence of phages on phagocytes is also important as such interactions may shape the immune response. In this review we have summarized the current knowledge on phage interactions with phagocytes described so far and their potential implications for phage therapy. The data suggesting that phage do not downregulate important phagocyte functions are especially relevant for the concept of phage therapy. PMID:28613272

Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics.

PubMed

Jończyk-Matysiak, Ewa; Weber-Dąbrowska, Beata; Owczarek, Barbara; Międzybrodzki, Ryszard; Łusiak-Szelachowska, Marzanna; Łodej, Norbert; Górski, Andrzej

2017-06-14

Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes-contained in granules-that are potentially toxic proteins. Therefore, it is important to investigate the possible interactions between phages and immune cells and avoid any phage side effects on them. Recent progress in knowledge concerning the influence of phages on phagocytes is also important as such interactions may shape the immune response. In this review we have summarized the current knowledge on phage interactions with phagocytes described so far and their potential implications for phage therapy . The data suggesting that phage do not downregulate important phagocyte functions are especially relevant for the concept of phage therapy.

Alteration of host-pathogen interactions in the wake of climate change - Increasing risk for shellfish associated infections?

PubMed

Hernroth, Bodil E; Baden, Susanne P

2018-02-01

The potential for climate-related spread of infectious diseases through marine systems has been highlighted in several reports. With this review we want to draw attention to less recognized mechanisms behind vector-borne transmission pathways to humans. We have focused on how the immune systems of edible marine shellfish, the blue mussels and Norway lobsters, are affected by climate related environmental stressors. Future ocean acidification (OA) and warming due to climate change constitute a gradually increasing persistent stress with negative trade-off for many organisms. In addition, the stress of recurrent hypoxia, inducing high levels of bioavailable manganese (Mn) is likely to increase in line with climate change. We summarized that OA, hypoxia and elevated levels of Mn did have an overall negative effect on immunity, in some cases also with synergistic effects. On the other hand, moderate increase in temperature seems to have a stimulating effect on antimicrobial activity and may in a future warming scenario counteract the negative effects. However, rising sea surface temperature and climate events causing high land run-off promote the abundance of naturally occurring pathogenic Vibrio and will in addition, bring enteric pathogens which are circulating in society into coastal waters. Moreover, the observed impairments of the immune defense enhance the persistence and occurrence of pathogens in shellfish. This may increase the risk for direct transmission of pathogens to consumers. It is thus essential that in the wake of climate change, sanitary control of coastal waters and seafood must recognize and adapt to the expected alteration of host-pathogen interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Identifying Regulators of the Immune Response to Dying Cells | Center for Cancer Research

Cancer.gov

Cytotoxic T cells are responsible for carrying out antigen-mediated immune responses against virally-infected and malignant cells. In both cases, cytotoxic T cells are stimulated by interacting with antigen presenting cells, such as dendritic cells (DCs). Infected cells produce virus-specific antigens and pathogen associated molecular patterns, which are recognized by DCs and

Emerging IL-12 family cytokines in the fight against fungal infections.

PubMed

Thompson, Aiysha; Orr, Selinda J

2018-05-21

Invasive fungal infections cause approximately 1.5 million deaths per year worldwide and are a growing threat to human health. Current anti-fungal therapies are often insufficient, therefore studies into host-pathogen interactions are critical for the development of novel therapies to improve mortality rates. Myeloid cells, such as macrophages and dendritic cells, express pattern recognition receptor (PRRs), which are important for fungal recognition. Engagement of these PRRs by fungal pathogens induces multiple cytokines, which in turn activate T effector responses. Interleukin (IL)-12 family members (IL-12p70, IL-23, IL-27 and IL-35) link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-12 and IL-23 have established roles during anti-fungal immunity, whereas emerging roles for IL-27 and IL-35 have recently been reported. Here, we discuss the IL-12 family, focusing on IL-27 and IL-35 during anti-fungal immune responses to pathogens such as Candida and Aspergillus. Copyright © 2018. Published by Elsevier Ltd.

NIK1-mediated translation suppression functions as a plant antiviral immunity mechanism.

PubMed

Zorzatto, Cristiane; Machado, João Paulo B; Lopes, Kênia V G; Nascimento, Kelly J T; Pereira, Welison A; Brustolini, Otávio J B; Reis, Pedro A B; Calil, Iara P; Deguchi, Michihito; Sachetto-Martins, Gilberto; Gouveia, Bianca C; Loriato, Virgílio A P; Silva, Marcos A C; Silva, Fabyano F; Santos, Anésia A; Chory, Joanne; Fontes, Elizabeth P B

2015-04-30

Plants and plant pathogens are subject to continuous co-evolutionary pressure for dominance, and the outcomes of these interactions can substantially impact agriculture and food security. In virus-plant interactions, one of the major mechanisms for plant antiviral immunity relies on RNA silencing, which is often suppressed by co-evolving virus suppressors, thus enhancing viral pathogenicity in susceptible hosts. In addition, plants use the nucleotide-binding and leucine-rich repeat (NB-LRR) domain-containing resistance proteins, which recognize viral effectors to activate effector-triggered immunity in a defence mechanism similar to that employed in non-viral infections. Unlike most eukaryotic organisms, plants are not known to activate mechanisms of host global translation suppression to fight viruses. Here we demonstrate in Arabidopsis that the constitutive activation of NIK1, a leucine-rich repeat receptor-like kinase (LRR-RLK) identified as a virulence target of the begomovirus nuclear shuttle protein (NSP), leads to global translation suppression and translocation of the downstream component RPL10 to the nucleus, where it interacts with a newly identified MYB-like protein, L10-INTERACTING MYB DOMAIN-CONTAINING PROTEIN (LIMYB), to downregulate translational machinery genes fully. LIMYB overexpression represses ribosomal protein genes at the transcriptional level, resulting in protein synthesis inhibition, decreased viral messenger RNA association with polysome fractions and enhanced tolerance to begomovirus. By contrast, the loss of LIMYB function releases the repression of translation-related genes and increases susceptibility to virus infection. Therefore, LIMYB links immune receptor LRR-RLK activation to global translation suppression as an antiviral immunity strategy in plants.

AMPK in Pathogens.

PubMed

Mesquita, Inês; Moreira, Diana; Sampaio-Marques, Belém; Laforge, Mireille; Cordeiro-da-Silva, Anabela; Ludovico, Paula; Estaquier, Jérôme; Silvestre, Ricardo

2016-01-01

During host-pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host-pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.

The early response during the interaction of fungal phytopathogen and host plant.

PubMed

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen; Zheng, Wenming

2017-05-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum , rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. © 2017 The Authors.

The early response during the interaction of fungal phytopathogen and host plant

PubMed Central

Shen, Yilin; Liu, Na; Li, Chuang; Wang, Xin; Xu, Xiaomeng; Chen, Wan; Xing, Guozhen

2017-01-01

Plants can be infected by a variety of pathogens, most of which can cause severe economic losses. The plants resist the invasion of pathogens via the innate or acquired immune system for surviving biotic stress. The associations between plants and pathogens are sophisticated beyond imaging and the interactions between them can occur at a very early stage after their touching each other. A number of researchers in the past decade have shown that many biochemical events appeared even as early as 5 min after their touching for plant disease resistance response. The early molecular interactions of plants and pathogens are likely to involve protein phosphorylation, ion fluxes, reactive oxygen species (ROS) and other signalling transduction. Here, we reviewed the recent progress in the study for molecular interaction response of fungal pathogens and host plant at the early infection stage, which included many economically important crop fungal pathogens such as cereal rust fungi, tomato Cladosporium fulvum, rice blast and so on. By dissecting the earlier infection stage of the diseases, the avirulent/virulent genes of pathogen or resistance genes of plant could be defined more clearly and accurately, which would undoubtedly facilitate fungal pathogenesis study and resistant crop breeding. PMID:28469008

Proteomic Analysis of the Relationship between Metabolism and Nonhost Resistance in Soybean Exposed to Bipolaris maydis.

PubMed

Dong, Yumei; Su, Yuan; Yu, Ping; Yang, Min; Zhu, Shusheng; Mei, Xinyue; He, Xiahong; Pan, Manhua; Zhu, Youyong; Li, Chengyun

2015-01-01

Nonhost resistance (NHR) pertains to the most common form of plant resistance against pathogenic microorganisms of other species. Bipolaris maydis is a non-adapted pathogen affecting soybeans, particularly of maize/soybean intercropping systems. However, no experimental evidence has described the immune response of soybeans against B. maydis. To elucidate the molecular mechanism underlying NHR in soybeans, proteomics analysis based on two-dimensional polyacrylamide gel electrophoresis (2-DE) was performed to identify proteins involved in the soybean response to B. maydis. The spread of B. maydis spores across soybean leaves induced NHR throughout the plant, which mobilized almost all organelles and various metabolic processes in response to B. maydis. Some enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), mitochondrial processing peptidase (MPP), oxygen evolving enhancer (OEE), and nucleoside diphosphate kinase (NDKs), were found to be related to NHR in soybeans. These enzymes have been identified in previous studies, and STRING analysis showed that most of the protein functions related to major metabolic processes were induced as a response to B. maydis, which suggested an array of complex interactions between soybeans and B. maydis. These findings suggest a systematic NHR against non-adapted pathogens in soybeans. This response was characterized by an overlap between metabolic processes and response to stimulus. Several metabolic processes provide the soybean with innate immunity to the non-adapted pathogen, B. maydis. This research investigation on NHR in soybeans may foster a better understanding of plant innate immunity, as well as the interactions between plant and non-adapted pathogens in intercropping systems.

Proteomic Analysis of the Relationship between Metabolism and Nonhost Resistance in Soybean Exposed to Bipolaris maydis

PubMed Central

Dong, Yumei; Su, Yuan; Yu, Ping; Yang, Min; Zhu, Shusheng; Mei, Xinyue; He, Xiahong; Pan, Manhua; Zhu, Youyong; Li, Chengyun

2015-01-01

Nonhost resistance (NHR) pertains to the most common form of plant resistance against pathogenic microorganisms of other species. Bipolaris maydis is a non-adapted pathogen affecting soybeans, particularly of maize/soybean intercropping systems. However, no experimental evidence has described the immune response of soybeans against B. maydis. To elucidate the molecular mechanism underlying NHR in soybeans, proteomics analysis based on two-dimensional polyacrylamide gel electrophoresis (2-DE) was performed to identify proteins involved in the soybean response to B. maydis. The spread of B. maydis spores across soybean leaves induced NHR throughout the plant, which mobilized almost all organelles and various metabolic processes in response to B. maydis. Some enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), mitochondrial processing peptidase (MPP), oxygen evolving enhancer (OEE), and nucleoside diphosphate kinase (NDKs), were found to be related to NHR in soybeans. These enzymes have been identified in previous studies, and STRING analysis showed that most of the protein functions related to major metabolic processes were induced as a response to B. maydis, which suggested an array of complex interactions between soybeans and B. maydis. These findings suggest a systematic NHR against non-adapted pathogens in soybeans. This response was characterized by an overlap between metabolic processes and response to stimulus. Several metabolic processes provide the soybean with innate immunity to the non-adapted pathogen, B. maydis. This research investigation on NHR in soybeans may foster a better understanding of plant innate immunity, as well as the interactions between plant and non-adapted pathogens in intercropping systems. PMID:26513657

The Magnaporthe oryzae effector AvrPiz-t targets the RING E3 ubiquitin ligase APIP6 to suppress pathogen-associated molecular pattern-triggered immunity in rice.

PubMed

Park, Chan-Ho; Chen, Songbiao; Shirsekar, Gautam; Zhou, Bo; Khang, Chang Hyun; Songkumarn, Pattavipha; Afzal, Ahmed J; Ning, Yuese; Wang, Ruyi; Bellizzi, Maria; Valent, Barbara; Wang, Guo-Liang

2012-11-01

Although the functions of a few effector proteins produced by bacterial and oomycete plant pathogens have been elucidated in recent years, information for the vast majority of pathogen effectors is still lacking, particularly for those of plant-pathogenic fungi. Here, we show that the avirulence effector AvrPiz-t from the rice blast fungus Magnaporthe oryzae preferentially accumulates in the specialized structure called the biotrophic interfacial complex and is then translocated into rice (Oryza sativa) cells. Ectopic expression of AvrPiz-t in transgenic rice suppresses the flg22- and chitin-induced generation of reactive oxygen species (ROS) and enhances susceptibility to M. oryzae, indicating that AvrPiz-t functions to suppress pathogen-associated molecular pattern (PAMP)-triggered immunity in rice. Interaction assays show that AvrPiz-t suppresses the ubiquitin ligase activity of the rice RING E3 ubiquitin ligase APIP6 and that, in return, APIP6 ubiquitinates AvrPiz-t in vitro. Interestingly, agroinfection assays reveal that AvrPiz-t and AvrPiz-t Interacting Protein 6 (APIP6) are both degraded when coexpressed in Nicotiana benthamiana. Silencing of APIP6 in transgenic rice leads to a significant reduction of flg22-induced ROS generation, suppression of defense-related gene expression, and enhanced susceptibility of rice plants to M. oryzae. Taken together, our results reveal a mechanism in which a fungal effector targets the host ubiquitin proteasome system for the suppression of PAMP-triggered immunity in plants.

Food for contagion: Synthesis and future directions for studying host–parasite responses to resource shifts in anthropogenic environments

PubMed Central

Altizer, Sonia. M.; Becker, Daniel J.; Epstein, Jonathan H.; Forbes, Kristian M.; Gillespie, Thomas R.; Hall, Richard J.; Hawley, Dana; Hernandez, Sonia M.; Martin, Lynn B.; Plowright, Raina K.; Satterfield, Dara A.; Streicker, Daniel G.

2018-01-01

Human-provided resource subsidies for wildlife are diverse, common, and have profound consequences for wildlife–pathogen interactions, as demonstrated by papers in this themed issue spanning empirical, theoretical, and management perspectives from a range of study systems. Contributions cut across scales of organization, from the within-host dynamics of immune function, to population-level impacts on parasite transmission, to landscape- and regional-scale patterns of infection. In this concluding paper, we identify common threads and key findings from author contributions, including the consequences of resource subsidies for (i) host immunity; (ii) animal aggregation and contact rates; (iii) host movement and landscape-level infection patterns; and (iv) inter-specific contacts and cross-species transmission. Exciting avenues for future work include studies that integrate mechanistic modeling and empirical approaches to better explore cross-scale processes, and experimental manipulations of food resources to quantify host and pathogen responses. Work is also needed to examine evolutionary responses to provisioning, and ask how diet-altered changes to the host microbiome influence infection processes. Given the massive public health and conservation implications of anthropogenic resource shifts, we end by underscoring the need for practical recommendations to manage supplemental feeding practices, limit human–wildlife conflicts over shared food resources, and reduce cross-species transmission risks, including to humans. PMID:29531154

Immune response of Staphylococcus aureus strains in a mouse mastitis model is linked to adaptive capacity and genotypic profiles.

PubMed

Pereyra, Elizabet A L; Sacco, Sofía C; Duré, Andrea; Baravalle, Celina; Renna, María S; Andreotti, Carolina S; Monecke, Stefan; Calvinho, Luis F; Dallard, Bibiana E

2017-05-01

Staphylococcus aureus is one of the most frequently isolated major pathogens from intramammary infections (IMI) worldwide. The mechanisms by which S. aureus IMI are established and maintained in dairy cows involve both bacterial escape strategies and modulation of the host immune response. Moreover, it was shown that different S. aureus strains have varying effects on the immune response. The aim of this study was to investigate the immune response in a mouse mastitis model of two S. aureus strains isolated from bovine IMI with different clinical manifestation (persistent-P or non-persistent-NP), phenotypic and genotypic profile. Both strains were capable of establishing an IMI after 264h post inoculation (pi). Strain A (NP) showed a more aggressive behaviour than strain B (P) at early stages of IMI, while strain B multiplied initially at a lower rate but increased its replication capacity from 120h pi to the end of the study (264h pi). Strain A triggered a stronger initial inflammatory response compared with strain B inducing higher gene and protein expression of TLR2, NF-κB activation and higher gene expression of IL-1α at initial stage of IMI (6-12h pi) but inducing extensive mammary tissue damage. Immune cells response was different for each S. aureus strain throughout the course of infection, showing mammary glands inoculated with strain A greater initial immune cells stimulation compared with strain B and then a second immune cells stimulation (from 120 to 264h pi) represented by monocytes-macrophages, T and B lymphocytes, mainly stimulated by strain B, consistent with inflammatory process becoming chronic. Strain-specific pathogenicity observed underscores the importance of pathogen factors in the progression of the infectious process. These results contribute to increase the available information on host-pathogen interaction and point out for the need of further research to expand the knowledge about these interactions for developing new strategies to intervene in the IMI progress. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of invertebrate infection models for pathogenic corynebacteria.

PubMed

Ott, Lisa; McKenzie, Ashleigh; Baltazar, Maria Teresa; Britting, Sabine; Bischof, Andrea; Burkovski, Andreas; Hoskisson, Paul A

2012-08-01

For several pathogenic bacteria, model systems for host-pathogen interactions were developed, which provide the possibility of quick and cost-effective high throughput screening of mutant bacteria for genes involved in pathogenesis. A number of different model systems, including amoeba, nematodes, insects, and fish, have been introduced, and it was observed that different bacteria respond in different ways to putative surrogate hosts, and distinct model systems might be more or less suitable for a certain pathogen. The aim of this study was to develop a suitable invertebrate model for the human and animal pathogens Corynebacterium diphtheriae, Corynebacterium pseudotuberculosis, and Corynebacterium ulcerans. The results obtained in this study indicate that Acanthamoeba polyphaga is not optimal as surrogate host, while both Caenorhabtitis elegans and Galleria larvae seem to offer tractable models for rapid assessment of virulence between strains. Caenorhabtitis elegans gives more differentiated results and might be the best model system for pathogenic corynebacteria, given the tractability of bacteria and the range of mutant nematodes available to investigate the host response in combination with bacterial virulence. Nevertheless, Galleria will also be useful in respect to innate immune responses to pathogens because insects offer a more complex cell-based innate immune system compared with the simple innate immune system of C. elegans. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Transcript profiling of the immunological interactions between Actinobacillus pleuropneumoniae serotype 7 and the host by dual RNA-seq.

PubMed

Li, Ping; Xu, Zhiwen; Sun, Xiangang; Yin, Yue; Fan, Yi; Zhao, Jun; Mao, Xiyu; Huang, Jianbo; Yang, Fan; Zhu, Ling

2017-09-12

The complexity of the pathogenic mechanism underlying the host immune response to Actinobacillus pleuropneumonia (App) makes the use of preventive measures difficult, and a more global view of the host-pathogen interactions and new insights into this process are urgently needed to reveal the pathogenic and immune mechanisms underlying App infection. Here, we infected specific pathogen-free Mus musculus with App serotype 7 by intranasal inoculation to construct an acute hemorrhagic pneumonia infection model and isolated the infected lungs for analysis of the interactions by dual RNA-seq. Four cDNA libraries were constructed, and 2428 differentially expressed genes (DEGs) of the host and 333 DEGs of App were detected. The host DEGs were mainly enriched in inflammatory signaling pathways, such as the TLR, NLR, RLR, BCR and TCR signaling pathways, resulting in large-scale cytokine up-regulation and thereby yielding a cytokine cascade for anti-infection and lung damage. The majority of the up-regulated cytokines are involved in the IL-23/IL-17 cytokine-regulated network, which is crucial for host defense against bacterial infection. The DEGs of App were mainly related to the transport and metabolism of energy and materials. Most of these genes are metabolic genes involved in anaerobic metabolism and important for challenging the host and adapting to the anaerobic stress conditions observed in acute hemorrhagic pneumonia. Some of these genes, such as adhE, dmsA, and aspA, might be potential virulence genes. In addition, the up-regulation of genes associated with peptidoglycan and urease synthesis and the restriction of major virulence genes might be immune evasion strategies of App. The regulation of metabolic genes and major virulence genes indicate that the dominant antigens might differ during the infection process and that vaccines based on these antigens might allow establishment of a precise and targeted immune response during the early phase of infection. Through an analysis of transcriptional data by dual RNA-seq, our study presents a novel global view of the interactions of App with its host and provides a basis for further study.

The immunological synapse

PubMed Central

Dustin, Michael L.

2015-01-01

The molecular interactions underlying regulation of the immune response take place in a nano-scale gap between T cells and antigen presenting cells, termed the immunological synapse. If these interactions are regulated appropriately, the host is defended against a wide range of pathogens and deranged host cells. If these interactions are dis-regulated, the host is susceptible to pathogens or tumor escape at one extreme and autoimmunity at the other. Treatments targeting the synapse have helped to establish immunotherapy as a mainstream element in cancer treatment. This Masters primer will cover the basics of the immunological synapse and some of the applications to tumor immunology. PMID:25367977

Abscisic Acid-Cytokinin Antagonism Modulates Resistance Against Pseudomonas syringae in Tobacco.

PubMed

Großkinsky, Dominik K; van der Graaff, Eric; Roitsch, Thomas

2014-12-01

Phytohormones are known as essential regulators of plant defenses, with ethylene, jasmonic acid, and salicylic acid as the central immunity backbone, while other phytohormones have been demonstrated to interact with this. Only recently, a function of the classic phytohormone cytokinin in plant immunity has been described in Arabidopsis, rice, and tobacco. Although interactions of cytokinins with salicylic acid and auxin have been indicated, the complete network of cytokinin interactions with other immunity-relevant phytohormones is not yet understood. Therefore, we studied the interaction of kinetin and abscisic acid as a negative regulator of plant immunity to modulate resistance in tobacco against Pseudomonas syringae. By analyzing infection symptoms, pathogen proliferation, and accumulation of the phytoalexin scopoletin as a key mediator of kinetin-induced resistance in tobacco, antagonistic interaction of these phytohormones in plant immunity was identified. Kinetin reduced abscisic acid levels in tobacco, while increased abscisic acid levels by exogenous application or inhibition of abscisic acid catabolism by diniconazole neutralized kinetin-induced resistance. Based on these results, we conclude that reduction of abscisic acid levels by enhanced abscisic acid catabolism strongly contributes to cytokinin-mediated resistance effects. Thus, the identified cytokinin-abscisic acid antagonism is a novel regulatory mechanism in plant immunity.

Review: Potential biotechnological assets related to plant immunity modulation applicable in engineering disease-resistant crops.

PubMed

Silva, Marilia Santos; Arraes, Fabrício Barbosa Monteiro; Campos, Magnólia de Araújo; Grossi-de-Sa, Maira; Fernandez, Diana; Cândido, Elizabete de Souza; Cardoso, Marlon Henrique; Franco, Octávio Luiz; Grossi-de-Sa, Maria Fátima

2018-05-01

This review emphasizes the biotechnological potential of molecules implicated in the different layers of plant immunity, including, pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), effector-triggered susceptibility (ETS), and effector-triggered immunity (ETI) that can be applied in the development of disease-resistant genetically modified (GM) plants. These biomolecules are produced by pathogens (viruses, bacteria, fungi, oomycetes) or plants during their mutual interactions. Biomolecules involved in the first layers of plant immunity, PTI and ETS, include inhibitors of pathogen cell-wall-degrading enzymes (CWDEs), plant pattern recognition receptors (PRRs) and susceptibility (S) proteins, while the ETI-related biomolecules include plant resistance (R) proteins. The biomolecules involved in plant defense PTI/ETI responses described herein also include antimicrobial peptides (AMPs), pathogenesis-related (PR) proteins and ribosome-inhibiting proteins (RIPs), as well as enzymes involved in plant defensive secondary metabolite biosynthesis (phytoanticipins and phytoalexins). Moreover, the regulation of immunity by RNA interference (RNAi) in GM disease-resistant plants is also considered. Therefore, the present review does not cover all the classes of biomolecules involved in plant innate immunity that may be applied in the development of disease-resistant GM crops but instead highlights the most common strategies in the literature, as well as their advantages and disadvantages. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Multi-Strain Deterministic Chaos in Dengue Epidemiology, A Challenge for Computational Mathematics

NASA Astrophysics Data System (ADS)

Aguiar, Maíra; Kooi, Bob W.; Stollenwerk, Nico

2009-09-01

Recently, we have analysed epidemiological models of competing strains of pathogens and hence differences in transmission for first versus secondary infection due to interaction of the strains with previously aquired immunities, as has been described for dengue fever, known as antibody dependent enhancement (ADE). These models show a rich variety of dynamics through bifurcations up to deterministic chaos. Including temporary cross-immunity even enlarges the parameter range of such chaotic attractors, and also gives rise to various coexisting attractors, which are difficult to identify by standard numerical bifurcation programs using continuation methods. A combination of techniques, including classical bifurcation plots and Lyapunov exponent spectra has to be applied in comparison to get further insight into such dynamical structures. Especially, Lyapunov spectra, which quantify the predictability horizon in the epidemiological system, are computationally very demanding. We show ways to speed up computations of such Lyapunov spectra by a factor of more than ten by parallelizing previously used sequential C programs. Such fast computations of Lyapunov spectra will be especially of use in future investigations of seasonally forced versions of the present models, as they are needed for data analysis.

Death Don't Have No Mercy and Neither Does Calcium: Arabidopsis CYCLIC NUCLEOTIDE GATED CHANNEL2 and Innate Immunity[W

PubMed Central

Ali, Rashid; Ma, Wei; Lemtiri-Chlieh, Fouad; Tsaltas, Dimitrios; Leng, Qiang; von Bodman, Susannne; Berkowitz, Gerald A.

2007-01-01

Plant innate immune response to pathogen infection includes an elegant signaling pathway leading to reactive oxygen species generation and resulting hypersensitive response (HR); localized programmed cell death in tissue surrounding the initial infection site limits pathogen spread. A veritable symphony of cytosolic signaling molecules (including Ca2+, nitric oxide [NO], cyclic nucleotides, and calmodulin) have been suggested as early components of HR signaling. However, specific interactions among these cytosolic secondary messengers and their roles in the signal cascade are still unclear. Here, we report some aspects of how plants translate perception of a pathogen into a signal cascade leading to an innate immune response. We show that Arabidopsis thaliana CYCLIC NUCLEOTIDE GATED CHANNEL2 (CNGC2/DND1) conducts Ca2+ into cells and provide a model linking this Ca2+ current to downstream NO production. NO is a critical signaling molecule invoking plant innate immune response to pathogens. Plants without functional CNGC2 lack this cell membrane Ca2+ current and do not display HR; providing the mutant with NO complements this phenotype. The bacterial pathogen–associated molecular pattern elicitor lipopolysaccharide activates a CNGC Ca2+ current, which may be linked to NO generation due to buildup of cytosolic Ca2+/calmodulin. PMID:17384171

Plant immunity against viruses: antiviral immune receptors in focus

PubMed Central

Calil, Iara P.

2017-01-01

Abstract Background Among the environmental limitations that affect plant growth, viruses cause major crop losses worldwide and represent serious threats to food security. Significant advances in the field of plant–virus interactions have led to an expansion of potential strategies for genetically engineered resistance in crops during recent years. Nevertheless, the evolution of viral virulence represents a constant challenge in agriculture that has led to a continuing interest in the molecular mechanisms of plant–virus interactions that affect disease or resistance. Scope and Conclusion This review summarizes the molecular mechanisms of the antiviral immune system in plants and the latest breakthroughs reported in plant defence against viruses. Particular attention is given to the immune receptors and transduction pathways in antiviral innate immunity. Plants counteract viral infection with a sophisticated innate immune system that resembles the non-viral pathogenic system, which is broadly divided into pathogen-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity. An additional recently uncovered virus-specific defence mechanism relies on host translation suppression mediated by a transmembrane immune receptor. In all cases, the recognition of the virus by the plant during infection is central for the activation of these innate defences, and, conversely, the detection of host plants enables the virus to activate virulence strategies. Plants also circumvent viral infection through RNA interference mechanisms by utilizing small RNAs, which are often suppressed by co-evolving virus suppressors. Additionally, plants defend themselves against viruses through hormone-mediated defences and activation of the ubiquitin–26S proteasome system (UPS), which alternatively impairs and facilitates viral infection. Therefore, plant defence and virulence strategies co-evolve and co-exist; hence, disease development is largely dependent on the extent and rate at which these opposing signals emerge in host and non-host interactions. A deeper understanding of plant antiviral immunity may facilitate innovative biotechnological, genetic and breeding approaches for crop protection and improvement. PMID:27780814

TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.

PubMed

Marchesan, Julie; Jiao, Yizu; Schaff, Riley A; Hao, Jie; Morelli, Thiago; Kinney, Janet S; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J; Inohara, Naohiro; Giannobile, William V

2016-06-01

Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

TLR4, NOD1 and NOD2 Mediate Immune Recognition of Putative Newly-Identified Periodontal Pathogens

PubMed Central

Schaff, Riley A.; Hao, Jie; Morelli, Thiago; Kinney, Janet S.; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J.; Inohara, Naohiro; Giannobile, William V.

2015-01-01

SUMMARY Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. While the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, 6 being classical pathogens and 4 putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone marrow–derived macrophages (BMDM) from wild-type (WT) and toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. C. concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney (HEK) cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2-stimulatory activity. These studies allowed us to provide important evidence on newly-identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). PMID:26177212

Neutrophil evasion strategies by Streptococcus pneumoniae and Staphylococcus aureus.

PubMed

Lewis, Megan L; Surewaard, Bas G J

2018-03-01

Humans are well equipped to defend themselves against bacteria. The innate immune system employs diverse mechanisms to recognize, control and initiate a response that can destroy millions of different microbes. Microbes that evade the sophisticated innate immune system are able to escape detection and could become pathogens. The pathogens Streptococcus pneumoniae and Staphylococcus aureus are particularly successful due to the development of a wide variety of virulence strategies for bacterial pathogenesis and they invest significant efforts towards mechanisms that allow for neutrophil evasion. Neutrophils are a primary cellular defense and can rapidly kill invading microbes, which is an indispensable function for maintaining host health. This review compares the key features of Streptococcus pneumoniae and Staphylococcus aureus in epidemiology, with a specific focus on virulence mechanisms utilized to evade neutrophils in bacterial pathogenesis. It is important to understand the complex interactions between pathogenic bacteria and neutrophils so that we can disrupt the ability of pathogens to cause disease.

Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs.

PubMed

Munguia, Jason; Nizet, Victor

2017-05-01

The rise of multidrug-resistant pathogens and the dearth of new antibiotic development place an existential strain on successful infectious disease therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health catastrophe. Reconceptualizing antibiotic therapy in the richer context of the host-pathogen interaction is required for innovative solutions. By defining specific virulence factors, the essence of a pathogen, and pharmacologically neutralizing their activities, one can block disease progression and sensitize microbes to immune clearance. Likewise, host-directed strategies to boost phagocyte bactericidal activity, enhance leukocyte recruitment, or reverse pathogen-induced immunosuppression seek to replicate the success of cancer immunotherapy in the field of infectious diseases. The answer to the threat of multidrug-resistant pathogens lies 'outside the box' of current antibiotic paradigms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar.

PubMed

Cárdenas, Constanza; Bidon-Chanal, Axel; Conejeros, Pablo; Arenas, Gloria; Marshall, Sergio; Luque, F Javier

2010-12-01

Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar (Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.

Recognition, survival and persistence of Staphylococcus aureus in the model host Tenebrio molitor.

PubMed

Dorling, Jack; Moraes, Caroline; Rolff, Jens

2015-02-01

The degree of specificity of any given immune response to a parasite is governed by the complexity and variation of interactions between host and pathogen derived molecules. Here, we assess the extent to which recognition and immuno-resistance of cell wall mutants of the pathogen Staphylococcus aureus may contribute to establishment and maintenance of persistent infection in the model insect host, Tenebrio molitor. The cell surface of S. aureus is decorated with various molecules, including glycopolymers such as wall teichoic acid (WTA). WTA is covalently bound to peptidoglycan (PGN) and its absence has been associated with increased recognition of PGN by host receptors (PGRPs). WTA is also further modified by other molecules such as D-alanine (D-alanylation). Both the level of WTA expression and its D-alanylation were found to be important in the mediation of the host-parasite interaction in this model system. Specifically, WTA itself was seen to influence immune recognition, while D-alanylation of WTA was found to increase immuno-resistance and was associated with prolonged persistence of S. aureus in T. molitor. These results implicate WTA and its D-alanylation as important factors in the establishment and maintenance of persistent infection, affecting different critical junctions in the immune response; through potential evasion of recognition by PGRPs and resistance to humoral immune effectors during prolonged exposure to the immune system. This highlights a mechanism by which specificity in this host-parasite interaction may arise. Copyright © 2014 Elsevier Ltd. All rights reserved.

Aspergillus fumigatus morphology and dynamic host interactions.

PubMed

van de Veerdonk, Frank L; Gresnigt, Mark S; Romani, Luigina; Netea, Mihai G; Latgé, Jean-Paul

2017-11-01

Aspergillus fumigatus is an environmental filamentous fungus that can cause life-threatening disease in immunocompromised individuals. The interactions between A. fumigatus and the host environment are dynamic and complex. The host immune system needs to recognize the distinct morphological forms of A. fumigatus to control fungal growth and prevent tissue invasion, whereas the fungus requires nutrients and needs to adapt to the hostile environment by escaping immune recognition and counteracting host responses. Understanding these highly dynamic interactions is necessary to fully understand the pathogenesis of aspergillosis and to facilitate the design of new therapeutics to overcome the morbidity and mortality caused by A. fumigatus. In this Review, we describe how A. fumigatus adapts to environmental change, the mechanisms of host defence, and our current knowledge of the interplay between the host immune response and the fungus.

Expression profiling during arabidopsis/downy mildew interaction reveals a highly-expressed effector that attenuates responses to salicylic acid.

PubMed

Asai, Shuta; Rallapalli, Ghanasyam; Piquerez, Sophie J M; Caillaud, Marie-Cécile; Furzer, Oliver J; Ishaque, Naveed; Wirthmueller, Lennart; Fabro, Georgina; Shirasu, Ken; Jones, Jonathan D G

2014-10-01

Plants have evolved strong innate immunity mechanisms, but successful pathogens evade or suppress plant immunity via effectors delivered into the plant cell. Hyaloperonospora arabidopsidis (Hpa) causes downy mildew on Arabidopsis thaliana, and a genome sequence is available for isolate Emoy2. Here, we exploit the availability of genome sequences for Hpa and Arabidopsis to measure gene-expression changes in both Hpa and Arabidopsis simultaneously during infection. Using a high-throughput cDNA tag sequencing method, we reveal expression patterns of Hpa predicted effectors and Arabidopsis genes in compatible and incompatible interactions, and promoter elements associated with Hpa genes expressed during infection. By resequencing Hpa isolate Waco9, we found it evades Arabidopsis resistance gene RPP1 through deletion of the cognate recognized effector ATR1. Arabidopsis salicylic acid (SA)-responsive genes including PR1 were activated not only at early time points in the incompatible interaction but also at late time points in the compatible interaction. By histochemical analysis, we found that Hpa suppresses SA-inducible PR1 expression, specifically in the haustoriated cells into which host-translocated effectors are delivered, but not in non-haustoriated adjacent cells. Finally, we found a highly-expressed Hpa effector candidate that suppresses responsiveness to SA. As this approach can be easily applied to host-pathogen interactions for which both host and pathogen genome sequences are available, this work opens the door towards transcriptome studies in infection biology that should help unravel pathogen infection strategies and the mechanisms by which host defense responses are overcome.

Targeting the C-type lectins-mediated host-pathogen interactions with dextran.

PubMed

Pustylnikov, Sergey; Sagar, Divya; Jain, Pooja; Khan, Zafar K

2014-01-01

Dextran, the α-1,6-linked glucose polymer widely used in biology and medicine, promises new applications. Linear dextran applied as a blood plasma substitute demonstrates a high rate of biocompatibility. Dextran is present in foods, drugs, and vaccines and in most cases is applied as a biologically inert substance. In this review we analyze dextran's cellular uptake principles, receptor specificity and, therefore, its ability to interfere with pathogen-lectin interactions: a promising basis for new antimicrobial strategies. Dextran-binding receptors in humans include the DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin) family receptors: DC-SIGN (CD209) and L-SIGN (the liver and lymphatic endothelium homologue of DC-SIGN), the mannose receptor (CD206), and langerin. These receptors take part in the uptake of pathogens by dendritic cells and macrophages and may also participate in the modulation of immune responses, mostly shown to be beneficial for pathogens per se rather than host(s). It is logical to predict that owing to receptor-specific interactions, dextran or its derivatives can interfere with these immune responses and improve infection outcome. Recent data support this hypothesis. We consider dextran a promising molecule for the development of lectin-glycan interaction-blocking molecules (such as DC-SIGN inhibitors) that could be applied in the treatment of diseases including tuberculosis, influenza, hepatitis B and C, human immunodeficiency virus infection and AIDS, etc. Dextran derivatives indeed change the pathology of infections dependent on DC-SIGN and mannose receptors. Complete knowledge of specific dextran-lectin interactions may also be important for development of future dextran applications in biological research and medicine.

SnTox1, a Parastagonospora nodorum necrotrophic effector, is a dual function protein that facilitates infection while protecting from wheat-produced chitinases

USDA-ARS?s Scientific Manuscript database

All fungal plant pathogens produce effectors to manipulate the plant immune system to colonize and gain nutrients from the plant cell. Much is known about how fungal pathogens classified as biotrophs use effectors to interact with their hosts and how the host responds, however, less is known about ...

PAMPs, PRRs, effectors and R-genes associated with citrus-pathogen interactions.

PubMed

Dalio, Ronaldo J D; Magalhães, Diogo M; Rodrigues, Carolina M; Arena, Gabriella D; Oliveira, Tiago S; Souza-Neto, Reinaldo R; Picchi, Simone C; Martins, Paula M M; Santos, Paulo J C; Maximo, Heros J; Pacheco, Inaiara S; De Souza, Alessandra A; Machado, Marcos A

2017-03-01

Recent application of molecular-based technologies has considerably advanced our understanding of complex processes in plant-pathogen interactions and their key components such as PAMPs, PRRs, effectors and R-genes. To develop novel control strategies for disease prevention in citrus, it is essential to expand and consolidate our knowledge of the molecular interaction of citrus plants with their pathogens. This review provides an overview of our understanding of citrus plant immunity, focusing on the molecular mechanisms involved in the interactions with viruses, bacteria, fungi, oomycetes and vectors related to the following diseases: tristeza, psorosis, citrus variegated chlorosis, citrus canker, huanglongbing, brown spot, post-bloom, anthracnose, gummosis and citrus root rot. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Two photon microscopy intravital study of DC-mediated anti-tumor response of NK cells

NASA Astrophysics Data System (ADS)

Caccia, Michele; Gorletta, Tatiana; Sironi, Laura; Zanoni, Ivan; Salvetti, Cristina; Collini, Maddalena; Granucci, Francesca; Chirico, Giuseppe

2010-02-01

Recent studies have demonstrated that dendritic cells (DCs) play a crucial role in the activation of Natural Killer cells (NKs) that are responsible for anti-tumor innate immune responses. The focus of this report is on the role of pathogen associated molecular pattern (PAMP) activated-DCs in inducing NK cell-mediated anti-tumor responses. Mice transplanted sub-cute (s.c.) with AK7 cells, a mesothelioma cell line sensitive to NK cell responses, are injected with fluorescent NK cells and DC activation is then induced by s.c. injection of Lipopolysaccharide (LPS). Using 4 dimensional tracking we follow the kinetic behavior of NK cells at the Draining Lymph-Node (DLN). As control, noninflammatory conditions are also evaluated. Our data suggest that NK cells are recruited to the DLN where they can interact with activated-DCs with a peculiar kinetic behavior: short lived interactions interleaved by rarer longer ones. We also found that the changes in the NK dynamic behavior in inflammatory conditions clearly affect relevant motility parameters such as the instantaneous and average velocity and the effective diffusion coefficient. This observation suggests that NK cells and activated-DCs might efficiently interact in the DLN, where cells could be activated. Therefore the interaction between activated-DCs and NK cells in DLN is not only a reality but it may be also crucial for the start of the immune response of the NKs.

Production of cross-kingdom oxylipins by pathogenic fungi: An update on their role in development and pathogenicity

PubMed Central

Fischer, Gregory J.; Keller, Nancy P.

2016-01-01

Oxylipins are a class of molecules derived from the incorporation of oxygen into polyunsaturated fatty acid substrates through the action of oxygenases. While extensively investigated in the context of mammalian immune responses, over the last decade it has become apparent that oxylipins are a common means of communication among and between plants, animals, and fungi to control development and alter host-microbe interactions. In fungi, some oxylipins are derived non-enzymatically while others are produced by lipoxygenases, cyclooxygenases, and monooxygenases with homology to plant and human enzymes. Recent investigations of numerous plant and human fungal pathogens have revealed oxylipins to be involved in the establishment and progression of disease This review highlights oxylipin production by pathogenic fungi and their role in fungal development and pathogen/host interactions. PMID:26920885

Inhibition of gold nanoparticles (AuNPs) on pathogenic biofilm formation and invasion to host cells.

PubMed

Yu, Qilin; Li, Jianrong; Zhang, Yueqi; Wang, Yufan; Liu, Lu; Li, Mingchun

2016-05-25

Owing to the growing infectious diseases caused by eukaryotic and prokaryotic pathogens, it is urgent to develop novel antimicrobial agents against clinical pathogenic infections. Biofilm formation and invasion into the host cells are vital processes during pathogenic colonization and infection. In this study, we tested the inhibitory effect of Au nanoparticles (AuNPs) on pathogenic growth, biofilm formation and invasion. Interestingly, although the synthesized AuNPs had no significant toxicity to the tested pathogens, Candida albicans and Pseudomonas aeruginosa, the nanoparticles strongly inhibited pathogenic biofilm formation and invasion to dental pulp stem cells (DPSCs). Further investigations revealed that AuNPs abundantly bound to the pathogen cells, which likely contributed to their inhibitory effect on biofilm formation and invasion. Moreover, treatment of AuNPs led to activation of immune response-related genes in DPSCs, which may enhance the activity of host immune system against the pathogens. Zeta potential analysis and polyethylene glycol (PEG)/polyethyleneimine (PEI) coating tests further showed that the interaction between pathogen cells and AuNPs is associated with electrostatic attractions. Our findings shed novel light on the application of nanomaterials in fighting against clinical pathogens, and imply that the traditional growth inhibition test is not the only way to evaluate the drug effect during the screening of antimicrobial agents.

Dynamic Modularity of Host Protein Interaction Networks in Salmonella Typhi Infection

PubMed Central

Dhal, Paltu Kumar; Barman, Ranjan Kumar; Saha, Sudipto; Das, Santasabuj

2014-01-01

Background Salmonella Typhi is a human-restricted pathogen, which causes typhoid fever and remains a global health problem in the developing countries. Although previously reported host expression datasets had identified putative biomarkers and therapeutic targets of typhoid fever, the underlying molecular mechanism of pathogenesis remains incompletely understood. Methods We used five gene expression datasets of human peripheral blood from patients suffering from S. Typhi or other bacteremic infections or non-infectious disease like leukemia. The expression datasets were merged into human protein interaction network (PIN) and the expression correlation between the hubs and their interacting proteins was measured by calculating Pearson Correlation Coefficient (PCC) values. The differences in the average PCC for each hub between the disease states and their respective controls were calculated for studied datasets. The individual hubs and their interactors with expression, PCC and average PCC values were treated as dynamic subnetworks. The hubs that showed unique trends of alterations specific to S. Typhi infection were identified. Results We identified S. Typhi infection-specific dynamic subnetworks of the host, which involve 81 hubs and 1343 interactions. The major enriched GO biological process terms in the identified subnetworks were regulation of apoptosis and biological adhesions, while the enriched pathways include cytokine signalling in the immune system and downstream TCR signalling. The dynamic nature of the hubs CCR1, IRS2 and PRKCA with their interactors was studied in detail. The difference in the dynamics of the subnetworks specific to S. Typhi infection suggests a potential molecular model of typhoid fever. Conclusions Hubs and their interactors of the S. Typhi infection-specific dynamic subnetworks carrying distinct PCC values compared with the non-typhoid and other disease conditions reveal new insight into the pathogenesis of S. Typhi. PMID:25144185

Cryptococcus interactions with macrophages: evasion and manipulation of the phagosome by a fungal pathogen.

PubMed

Johnston, Simon A; May, Robin C

2013-03-01

Cryptococcus is a potentially fatal fungal pathogen and a leading cause of death in immunocompromised patients. As an opportunistic and facultative intracellular pathogen of humans, Cryptococcus exhibits a complex set of interactions with the host immune system in general, and macrophages in particular. Cryptococcus is resistant to phagocytosis but is also able to survive and proliferate within the mature phagolysosome. It can cause the lysis of host cells, can be transferred between macrophages or exit non-lytically via vomocytosis. Efficient phagocytosis is reliant on opsonization and Cryptococcus has a number of anti-phagocytic strategies including formation of titan cells and a thick polysaccharide capsule. Following uptake, phagosome maturation appears to occur normally, but the internalized pathogen is able to survive and replicate. Here we review the interactions and host manipulation processes that occur within cryptococcal-infected macrophages and highlight areas for future research. © 2012 Blackwell Publishing Ltd.

Evolution of Salmonella-Host Cell Interactions through a Dynamic Bacterial Genome

PubMed Central

Ilyas, Bushra; Tsai, Caressa N.; Coombes, Brian K.

2017-01-01

Salmonella Typhimurium has a broad arsenal of genes that are tightly regulated and coordinated to facilitate adaptation to the various host environments it colonizes. The genome of Salmonella Typhimurium has undergone multiple gene acquisition events and has accrued changes in non-coding DNA that have undergone selection by regulatory evolution. Together, at least 17 horizontally acquired pathogenicity islands (SPIs), prophage-associated genes, and changes in core genome regulation contribute to the virulence program of Salmonella. Here, we review the latest understanding of these elements and their contributions to pathogenesis, emphasizing the regulatory circuitry that controls niche-specific gene expression. In addition to an overview of the importance of SPI-1 and SPI-2 to host invasion and colonization, we describe the recently characterized contributions of other SPIs, including the antibacterial activity of SPI-6 and adhesion and invasion mediated by SPI-4. We further discuss how these fitness traits have been integrated into the regulatory circuitry of the bacterial cell through cis-regulatory evolution and by a careful balance of silencing and counter-silencing by regulatory proteins. Detailed understanding of regulatory evolution within Salmonella is uncovering novel aspects of infection biology that relate to host-pathogen interactions and evasion of host immunity. PMID:29034217

Immunogene and viral transcript dynamics during parasitic Varroa destructor mite infection of developing honey bee (Apis mellifera) pupae.

PubMed

Kuster, Ryan D; Boncristiani, Humberto F; Rueppell, Olav

2014-05-15

The ectoparasitic Varroa destructor mite is a major contributor to the ongoing honey bee health crisis. Varroa interacts with honey bee viruses, exacerbating their pathogenicity. In addition to vectoring viruses, immunosuppression of the developing honey bee hosts by Varroa has been proposed to explain the synergy between viruses and mites. However, the evidence for honey bee immune suppression by V. destructor is contentious. We systematically studied the quantitative effects of experimentally introduced V. destructor mites on immune gene expression at five specific time points during the development of the honey bee hosts. Mites reproduced normally and were associated with increased titers of deformed wing virus in the developing bees. Our data on different immune genes show little evidence for immunosuppression of honey bees by V. destructor. Experimental wounding of developing bees increases relative immune gene expression and deformed wing virus titers. Combined, these results suggest that mite feeding activity itself and not immunosuppression may contribute to the synergy between viruses and mites. However, our results also suggest that increased expression of honey bee immune genes decreases mite reproductive success, which may be explored to enhance mite control strategies. Finally, our expression data for multiple immune genes across developmental time and different experimental treatments indicates co-regulation of several of these genes and thus improves our understanding of the understudied honey bee immune system. © 2014. Published by The Company of Biologists Ltd.

Exploring the Homeostatic and Sensory Roles of the Immune System.

PubMed

Marques, Rafael Elias; Marques, Pedro Elias; Guabiraba, Rodrigo; Teixeira, Mauro Martins

2016-01-01

Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection.

Transcriptomic analysis reveals tomato genes whose expression is induced specifically during effector-triggered immunity and identifies the Epk1 protein kinase which is required for the host response to three bacterial effector proteins.

PubMed

Pombo, Marina A; Zheng, Yi; Fernandez-Pozo, Noe; Dunham, Diane M; Fei, Zhangjun; Martin, Gregory B

2014-01-01

Plants have two related immune systems to defend themselves against pathogen attack. Initially,pattern-triggered immunity is activated upon recognition of microbe-associated molecular patterns by pattern recognition receptors. Pathogenic bacteria deliver effector proteins into the plant cell that interfere with this immune response and promote disease. However, some plants express resistance proteins that detect the presence of specific effectors leading to a robust defense response referred to as effector-triggered immunity. The interaction of tomato with Pseudomonas syringae pv. tomato is an established model system for understanding the molecular basis of these plant immune responses. We apply high-throughput RNA sequencing to this pathosystem to identify genes whose expression changes specifically during pattern-triggered or effector-triggered immunity. We then develop reporter genes for each of these responses that will enable characterization of the host response to the large collection of P. s. pv. tomato strains that express different combinations of effectors. Virus-induced gene silencing of 30 of the effector-triggered immunity-specific genes identifies Epk1 which encodes a predicted protein kinase from a family previously unknown to be involved in immunity. Knocked-down expression of Epk1 compromises effector-triggered immunity triggered by three bacterial effectors but not by effectors from non-bacterial pathogens. Epistasis experiments indicate that Epk1 acts upstream of effector-triggered immunity-associated MAP kinase signaling. Using RNA-seq technology we identify genes involved in specific immune responses. A functional genomics screen led to the discovery of Epk1, a novel predicted protein kinase required for plant defense activation upon recognition of three different bacterial effectors.

Competition between influenza A virus subtypes through heterosubtypic immunity modulates re-infection and antibody dynamics in the mallard duck.

PubMed

Latorre-Margalef, Neus; Brown, Justin D; Fojtik, Alinde; Poulson, Rebecca L; Carter, Deborah; Franca, Monique; Stallknecht, David E

2017-06-01

Our overall hypothesis is that host population immunity directed at multiple antigens will influence the prevalence, diversity and evolution of influenza A virus (IAV) in avian populations where the vast subtype diversity is maintained. To investigate how initial infection influences the outcome of later infections with homologous or heterologous IAV subtypes and how viruses interact through host immune responses, we carried out experimental infections in mallard ducks (Anas platyrhynchos). Mallards were pre-challenged with an H3N8 low-pathogenic IAV and were divided into six groups. At five weeks post H3N8 inoculation, each group was challenged with a different IAV subtype (H4N5, H10N7, H6N2, H12N5) or the same H3N8. Two additional pre-challenged groups were inoculated with the homologous H3N8 virus at weeks 11 and 15 after pre-challenge to evaluate the duration of protection. The results showed that mallards were still resistant to re-infection after 15 weeks. There was a significant reduction in shedding for all pre-challenged groups compared to controls and the outcome of the heterologous challenges varied according to hemagglutinin (HA) phylogenetic relatedness between the viruses used. There was a boost in the H3 antibody titer after re-infection with H4N5, which is consistent with original antigenic sin or antigenic seniority and suggest a putative strategy of virus evasion. These results imply competition between related subtypes that could regulate IAV subtype population dynamics in nature. Collectively, we provide new insights into within-host IAV complex interactions as drivers of IAV antigenic diversity that could allow the circulation of multiple subtypes in wild ducks.

Competition between influenza A virus subtypes through heterosubtypic immunity modulates re-infection and antibody dynamics in the mallard duck

PubMed Central

Brown, Justin D.; Carter, Deborah; Franca, Monique; Stallknecht, David E.

2017-01-01

Our overall hypothesis is that host population immunity directed at multiple antigens will influence the prevalence, diversity and evolution of influenza A virus (IAV) in avian populations where the vast subtype diversity is maintained. To investigate how initial infection influences the outcome of later infections with homologous or heterologous IAV subtypes and how viruses interact through host immune responses, we carried out experimental infections in mallard ducks (Anas platyrhynchos). Mallards were pre-challenged with an H3N8 low-pathogenic IAV and were divided into six groups. At five weeks post H3N8 inoculation, each group was challenged with a different IAV subtype (H4N5, H10N7, H6N2, H12N5) or the same H3N8. Two additional pre-challenged groups were inoculated with the homologous H3N8 virus at weeks 11 and 15 after pre-challenge to evaluate the duration of protection. The results showed that mallards were still resistant to re-infection after 15 weeks. There was a significant reduction in shedding for all pre-challenged groups compared to controls and the outcome of the heterologous challenges varied according to hemagglutinin (HA) phylogenetic relatedness between the viruses used. There was a boost in the H3 antibody titer after re-infection with H4N5, which is consistent with original antigenic sin or antigenic seniority and suggest a putative strategy of virus evasion. These results imply competition between related subtypes that could regulate IAV subtype population dynamics in nature. Collectively, we provide new insights into within-host IAV complex interactions as drivers of IAV antigenic diversity that could allow the circulation of multiple subtypes in wild ducks. PMID:28640898

Host-pathogen interplay in the respiratory environment of cystic fibrosis.

PubMed

Yonker, Lael M; Cigana, Cristina; Hurley, Bryan P; Bragonzi, Alessandra

2015-07-01

Significant advances have been made in the understanding of disease progression in cystic fibrosis (CF), revealing a complex interplay between host and pathogenic organisms. The diverse CF microbiota within the airway activates an aberrant immune response that is ineffective in clearing infection. An appreciation of how the CF host immune system interacts with these organisms is crucial to understanding the pathogenesis of CF pulmonary disease. Here we discuss the microbial complexity present in the lungs of individuals with CF, review emerging concepts of innate and adaptive immune responses to pathogens that chronically inhabit the CF lung, and discuss therapies that target the aberrant inflammatory response that characterizes CF. A greater understanding of the underlying mechanisms will shed light on pathogenesis and guide more targeted therapies in the future that serve to reduce infection, minimize lung pathology, and improve the quality of life for patients with CF. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

The Peyer’s Patch Mononuclear Phagocyte System at Steady State and during Infection

PubMed Central

Da Silva, Clément; Wagner, Camille; Bonnardel, Johnny; Gorvel, Jean-Pierre; Lelouard, Hugues

2017-01-01

The gut represents a potential entry site for a wide range of pathogens including protozoa, bacteria, viruses, or fungi. Consequently, it is protected by one of the largest and most diversified population of immune cells of the body. Its surveillance requires the constant sampling of its encounters by dedicated sentinels composed of follicles and their associated epithelium located in specialized area. In the small intestine, Peyer’s patches (PPs) are the most important of these mucosal immune response inductive sites. Through several mechanisms including transcytosis by specialized epithelial cells called M-cells, access to the gut lumen is facilitated in PPs. Although antigen sampling is critical to the initiation of the mucosal immune response, pathogens have evolved strategies to take advantage of this permissive gateway to enter the host and disseminate. It is, therefore, critical to decipher the mechanisms that underlie both host defense and pathogen subversive strategies in order to develop new mucosal-based therapeutic approaches. Whereas penetration of pathogens through M cells has been well described, their fate once they have reached the subepithelial dome (SED) remains less well understood. Nevertheless, it is clear that the mononuclear phagocyte system (MPS) plays a critical role in handling these pathogens. MPS members, including both dendritic cells and macrophages, are indeed strongly enriched in the SED, interact with M cells, and are necessary for antigen presentation to immune effector cells. This review focuses on recent advances, which have allowed distinguishing the different PP mononuclear phagocyte subsets. It gives an overview of their diversity, specificity, location, and functions. Interaction of PP phagocytes with the microbiota and the follicle-associated epithelium as well as PP infection studies are described in the light of these new criteria of PP phagocyte identification. Finally, known alterations affecting the different phagocyte subsets during PP stimulation or infection are discussed. PMID:29038658

A Pathogenic Nematode Targets Recognition Proteins to Avoid Insect Defenses

PubMed Central

Toubarro, Duarte; Avila, Mónica Martinez; Montiel, Rafael; Simões, Nelson

2013-01-01

Steinernema carpocapsae is a nematode pathogenic in a wide variety of insect species. The great pathogenicity of this nematode has been ascribed to its ability to overcome the host immune response; however, little is known about the mechanisms involved in this process. The analysis of an expressed sequence tags (EST) library in the nematode during the infective phase was performed and a highly abundant contig homologous to serine protease inhibitors was identified. In this work, we show that this contig is part of a 641-bp cDNA that encodes a BPTI-Kunitz family inhibitor (Sc-KU-4), which is up-regulated in the parasite during invasion and installation. Recombinant Sc-KU-4 protein was produced in Escherichia coli and shown to inhibit chymotrypsin and elastase activities in a dose-dependent manner by a competitive mechanism with Ki values of 1.8 nM and 2.6 nM, respectively. Sc-KU-4 also inhibited trypsin and thrombin activities to a lesser extent. Studies of the mode of action of Sc-KU-4 and its effects on insect defenses suggest that although Sc-KU-4 did not inhibit the activation of hemocytes or the formation of clotting fibers, it did inhibit hemocyte aggregation and the entrapment of foreign particles by fibers. Moreover, Sc-KU-4 avoided encapsulation and the deposition of clotting materials, which usually occurs in response to foreign particles. We show by protein-protein interaction that Sc-KU-4 targets recognition proteins of insect immune system such as masquerade-like and serine protease-like homologs. The interaction of Sc-KU-4 with these proteins explains the ability of the nematode to overcome host reactions and its large pathogenic spectrum, once these immune proteins are well conserved in insects. The discovery of this inhibitor targeting insect recognition proteins opens new avenues for the development of S . carpocapsae as a biological control agent and provides a new tool to study host-pathogen interactions. PMID:24098715

Host plant associated enhancement of immunity and survival in virus infected caterpillars.

PubMed

Smilanich, Angela M; Langus, Tara C; Doan, Lydia; Dyer, Lee A; Harrison, Joshua G; Hsueh, Jennifer; Teglas, Mike B

2018-01-01

Understanding the interaction between host plant chemistry, the immune response, and insect pathogens can shed light on host plant use by insect herbivores. In this study, we focused on how interactions between the insect immune response and plant secondary metabolites affect the response to a viral pathogen. Based upon prior research, we asked whether the buckeye caterpillar, Junonia coenia (Nymphalidae), which specializes on plants containing iridoid glycosides (IGs), is less able to resist the pathogenic effects of a densovirus infection when feeding on plants with high concentrations of IGs. In a fully factorial design, individuals were randomly assigned to three treatments, each of which had two levels: (1) exposed to the densovirus versus control, (2) placed on a plant species with high concentrations of IGs (Plantago lanceolata, Plantaginaceae) versus low concentrations of IGs (P. major), and (3) control versus surface sterilized to exclude surface microbes that may contribute to viral resistance. We measured phenoloxidase (PO) activity, hemocyte counts, and gut bacterial diversity (16S ribosomal RNA) during the fourth larval instar, as well as development time, pupal weight, and survival to adult. Individuals infected with the virus were immune-suppressed (as measured by PO response and hemocyte count) and developed significantly faster than virus-free individuals. Contrary to our predictions,mortality was significantly less for virus challengedindividuals reared on the high IG plant compared to the low IG plant.This suggests that plant secondary metabolites can influence survival from viral infection and may be associated with activation of PO. Removing egg microbes did not affect the immune response or survival of the larvae. In summary, these results suggest that plant secondary metabolites are important for survival against a viral pathogen. Even though the PO response was better on the high IG plant, the extent to which this result contributes to survival against the virus needs further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Genes, communities & invasive species: understanding the ecological and evolutionary dynamics of host-pathogen interactions.

PubMed

Burdon, J J; Thrall, P H; Ericson, L

2013-08-01

Reciprocal interactions between hosts and pathogens drive ecological, epidemiological and co-evolutionary trajectories, resulting in complex patterns of diversity at population, species and community levels. Recent results confirm the importance of negative frequency-dependent rather than 'arms-race' processes in the evolution of individual host-pathogen associations. At the community level, complex relationships between species abundance and diversity dampen or alter pathogen impacts. Invasive pathogens challenge these controls reflecting the earliest stages of evolutionary associations (akin to arms-race) where disease effects may be so great that they overwhelm the host's and community's ability to respond. Viewing these different stabilization/destabilization phases as a continuum provides a valuable perspective to assessment of the role of genetics and ecology in the dynamics of both natural and invasive host-pathogen associations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Go in for the kill: How plants deploy effector-triggered immunity to combat pathogens. [Corrected].

PubMed

Wu, Liang; Chen, Huan; Curtis, Chad; Fu, Zheng Qing

2014-01-01

Plant resistance (R) proteins perceive specific pathogen effectors from diverse plant pathogens to initiate defense responses, designated effector-triggered immunity (ETI). Plant R proteins are mostly nucleotide binding-leucine rich repeat (NB-LRR) proteins, which recognize pathogen effectors directly or indirectly through sophisticated mechanisms. Upon activation by effector proteins, R proteins elicit robust defense responses, including a rapid burst of reactive oxygen species (ROS), induced biosynthesis and accumulation of salicylic acid (SA), a rapid programmed cell death (PCD) called hypersensitive response (HR) at the infection sites, and increased expression of pathogenesis-related (PR) genes. Initiation of ETI is correlated with a complex network of defense signaling pathways, resulting in defensive cellular responses and large-scale transcriptional reprogramming events. In this review, we highlight important recent advances on the recognition of effectors, regulation and activation of plant R proteins, dynamic intracellular trafficking of R proteins, induction of cell death, and transcriptional reprogramming associated with ETI. Current knowledge gaps and future research directions are also discussed in this review.

Plant pattern recognition receptor complexes at the plasma membrane.

PubMed

Monaghan, Jacqueline; Zipfel, Cyril

2012-08-01

A key feature of innate immunity is the ability to recognize and respond to potential pathogens in a highly sensitive and specific manner. In plants, the activation of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) elicits a defense programme known as PAMP-triggered immunity (PTI). Although only a handful of PAMP-PRR pairs have been defined, all known PRRs are modular transmembrane proteins containing ligand-binding ectodomains. It is becoming clear that PRRs do not act alone but rather function as part of multi-protein complexes at the plasma membrane. Recent studies describing the molecular interactions and protein modifications that occur between PRRs and their regulatory proteins have provided important mechanistic insight into how plants avoid infection and achieve immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

TCP three-way handshake: linking developmental processes with plant immunity.

PubMed

Lopez, Jessica A; Sun, Yali; Blair, Peter B; Mukhtar, M Shahid

2015-04-01

The TCP gene family encodes plant-specific transcription factors involved in growth and development. Equally important are the interactions between TCP factors and other pathways extending far beyond development, as they have been found to regulate a variety of hormonal pathways and signaling cascades. Recent advances reveal that TCP factors are targets of pathogenic effectors and are likely to play a vital role in plant immunity. Our focus is on reviewing the involvement of TCP in known pathways and shedding light on other linkages in the nexus of plant immunity centered around TCP factors with an emphasis on the convergence of effectors, interconnected hormonal networks, utility of the circadian clock, and the potential mechanisms by which pathogen defense may occur. Copyright © 2015 Elsevier Ltd. All rights reserved.

Borrelia burgdorferi protein interactions critical for microbial persistence in mammals.

PubMed

Bernard, Quentin; Thakur, Meghna; Smith, Alexis A; Kitsou, Chrysoula; Yang, Xiuli; Pal, Utpal

2018-06-22

Borrelia burgdorferi is the causative agent of Lyme disease that persists in a complex enzootic life cycle, involving Ixodes ticks and vertebrate hosts. The microbe invades ticks and vertebrate hosts in spite of active immune surveillance and potent microbicidal responses, and establishes long-term infection utilizing mechanisms that are yet to be unraveled. The pathogen can cause multi-system disorders when transmitted to susceptible mammalian hosts, including in humans. In the past decades, several studies identified a limited number of B. burgdorferi gene-products critical for pathogen persistence, transmission between the vectors and the host, and host-pathogen interactions. This review will focus on the interactions between B. burgdorferi proteins, as well between microbial proteins and host components, protein and non-protein components, highlighting their roles in pathogen persistence in the mammalian host. A better understanding of the contributions of protein interactions in the microbial virulence and persistence of B. burgdorferi would support development of novel therapeutics against the infection. This article is protected by copyright. All rights reserved.

IFN-β: A Contentious Player in Host–Pathogen Interaction in Tuberculosis

PubMed Central

Sabir, Naveed; Hussain, Tariq; Shah, Syed Zahid Ali; Zhao, Deming; Zhou, Xiangmei

2017-01-01

Tuberculosis (TB) is a major health threat to the human population worldwide. The etiology of the disease is Mycobacterium tuberculosis (Mtb), a highly successful intracellular pathogen. It has the ability to manipulate the host immune response and to make the intracellular environment suitable for its survival. Many studies have addressed the interactions between the bacteria and the host immune cells as involving many immune mediators and other cellular players. Interferon-β (IFN-β) signaling is crucial for inducing the host innate immune response and it is an important determinant in the fate of mycobacterial infection. The role of IFN-β in protection against viral infections is well established and has been studied for decades, but its role in mycobacterial infections remains much more complicated and debatable. The involvement of IFN-β in immune evasion mechanisms adopted by Mtb has been an important area of investigation in recent years. These advances have widened our understanding of the pro-bacterial role of IFN-β in host–pathogen interactions. This pro-bacterial activity of IFN-β appears to be correlated with its anti-inflammatory characteristics, primarily by antagonizing the production and function of interleukin 1β (IL-1β) and interleukin 18 (IL-18) through increased interleukin 10 (IL-10) production and by inhibiting the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome. Furthermore, it also fails to provoke a proper T helper 1 (Th1) response and reduces the expression of major histocompatibility complex II (MHC-II) and interferon-γ receptors (IFNGRs). Here we will review some studies to provide a paradigm for the induction, regulation, and role of IFN-β in mycobacterial infection. Indeed, recent studies suggest that IFN-β plays a role in Mtb survival in host cells and its downregulation may be a useful therapeutic strategy to control Mtb infection. PMID:29258190

IFN-β: A Contentious Player in Host-Pathogen Interaction in Tuberculosis.

PubMed

Sabir, Naveed; Hussain, Tariq; Shah, Syed Zahid Ali; Zhao, Deming; Zhou, Xiangmei

2017-12-16

Tuberculosis (TB) is a major health threat to the human population worldwide. The etiology of the disease is Mycobacterium tuberculosis (Mtb), a highly successful intracellular pathogen. It has the ability to manipulate the host immune response and to make the intracellular environment suitable for its survival. Many studies have addressed the interactions between the bacteria and the host immune cells as involving many immune mediators and other cellular players. Interferon-β (IFN-β) signaling is crucial for inducing the host innate immune response and it is an important determinant in the fate of mycobacterial infection. The role of IFN-β in protection against viral infections is well established and has been studied for decades, but its role in mycobacterial infections remains much more complicated and debatable. The involvement of IFN-β in immune evasion mechanisms adopted by Mtb has been an important area of investigation in recent years. These advances have widened our understanding of the pro-bacterial role of IFN-β in host-pathogen interactions. This pro-bacterial activity of IFN-β appears to be correlated with its anti-inflammatory characteristics, primarily by antagonizing the production and function of interleukin 1β (IL-1β) and interleukin 18 (IL-18) through increased interleukin 10 (IL-10) production and by inhibiting the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome. Furthermore, it also fails to provoke a proper T helper 1 (Th1) response and reduces the expression of major histocompatibility complex II (MHC-II) and interferon-γ receptors (IFNGRs). Here we will review some studies to provide a paradigm for the induction, regulation, and role of IFN-β in mycobacterial infection. Indeed, recent studies suggest that IFN-β plays a role in Mtb survival in host cells and its downregulation may be a useful therapeutic strategy to control Mtb infection.

Modelling the effects of phylogeny and body size on within-host pathogen replication and immune response.

PubMed

Banerjee, Soumya; Perelson, Alan S; Moses, Melanie

2017-11-01

Understanding how quickly pathogens replicate and how quickly the immune system responds is important for predicting the epidemic spread of emerging pathogens. Host body size, through its correlation with metabolic rates, is theoretically predicted to impact pathogen replication rates and immune system response rates. Here, we use mathematical models of viral time courses from multiple species of birds infected by a generalist pathogen (West Nile Virus; WNV) to test more thoroughly how disease progression and immune response depend on mass and host phylogeny. We use hierarchical Bayesian models coupled with nonlinear dynamical models of disease dynamics to incorporate the hierarchical nature of host phylogeny. Our analysis suggests an important role for both host phylogeny and species mass in determining factors important for viral spread such as the basic reproductive number, WNV production rate, peak viraemia in blood and competency of a host to infect mosquitoes. Our model is based on a principled analysis and gives a quantitative prediction for key epidemiological determinants and how they vary with species mass and phylogeny. This leads to new hypotheses about the mechanisms that cause certain taxonomic groups to have higher viraemia. For example, our models suggest that higher viral burst sizes cause corvids to have higher levels of viraemia and that the cellular rate of virus production is lower in larger species. We derive a metric of competency of a host to infect disease vectors and thereby sustain the disease between hosts. This suggests that smaller passerine species are highly competent at spreading the disease compared with larger non-passerine species. Our models lend mechanistic insight into why some species (smaller passerine species) are pathogen reservoirs and some (larger non-passerine species) are potentially dead-end hosts for WNV. Our techniques give insights into the role of body mass and host phylogeny in the spread of WNV and potentially other zoonotic diseases. The major contribution of this work is a computational framework for infectious disease modelling at the within-host level that leverages data from multiple species. This is likely to be of interest to modellers of infectious diseases that jump species barriers and infect multiple species. Our method can be used to computationally determine the competency of a host to infect mosquitoes that will sustain WNV and other zoonotic diseases. We find that smaller passerine species are more competent in spreading the disease than larger non-passerine species. This suggests the role of host phylogeny as an important determinant of within-host pathogen replication. Ultimately, we view our work as an important step in linking within-host viral dynamics models to between-host models that determine spread of infectious disease between different hosts. © 2017 The Author(s).

Can Horton hear the whos? The importance of scale in mosquito-borne disease.

PubMed

Lord, C C; Alto, B W; Anderson, S L; Connelly, C R; Day, J F; Richards, S L; Smartt, C T; Tabachnick, W J

2014-03-01

The epidemiology of vector-borne pathogens is determined by mechanisms and interactions at different scales of biological organization, from individual-level cellular processes to community interactions between species and with the environment. Most research, however, focuses on one scale or level with little integration between scales or levels within scales. Understanding the interactions between levels and how they influence our perception of vector-borne pathogens is critical. Here two examples of biological scales (pathogen transmission and mosquito mortality) are presented to illustrate some of the issues of scale and to explore how processes on different levels may interact to influence mosquito-borne pathogen transmission cycles. Individual variation in survival, vector competence, and other traits affect population abundance, transmission potential, and community structure. Community structure affects interactions between individuals such as competition and predation, and thus influences the individual-level dynamics and transmission potential. Modeling is a valuable tool to assess interactions between scales and how processes at different levels can affect transmission dynamics. We expand an existing model to illustrate the types of studies needed, showing that individual-level variation in viral dose acquired or needed for infection can influence the number of infectious vectors. It is critical that interactions within and among biological scales and levels of biological organization are understood for greater understanding of pathogen transmission with the ultimate goal of improving control of vector-borne pathogens.

Large Variations in HIV-1 Viral Load Explained by Shifting-Mosaic Metapopulation Dynamics

PubMed Central

Lythgoe, Katrina A.; Blanquart, François

2016-01-01

The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models. We study the dynamics of virus replication and cytotoxic T lymphocytes (CTLs) within a metapopulation of spatially segregated patches, representing T cell areas connected by circulating blood and lymph. The dynamics of the system depend critically on the interaction between CTLs and infected cells at the within-patch level. We show that for a wide range of parameters, the system admits an unexpected outcome called the shifting-mosaic steady state. In this state, the whole body’s viral population is stable over time, but the equilibrium results from an underlying, highly dynamic process of local infection and clearance within T-cell centers. Notably, and in contrast to previous models, this new model can explain the large differences in set-point viral load (SPVL) observed between patients and their distribution, as well as the relatively low proportion of cells infected at any one time, and alters the predicted determinants of viral load variation. PMID:27706164

Monitoring dynamic interactions of tumor cells with tissue and immune cells in a lab-on-a-chip.

PubMed

Charwat, Verena; Rothbauer, Mario; Tedde, Sandro F; Hayden, Oliver; Bosch, Jacobus J; Muellner, Paul; Hainberger, Rainer; Ertl, Peter

2013-12-03

A complementary cell analysis method has been developed to assess the dynamic interactions of tumor cells with resident tissue and immune cells using optical light scattering and impedance sensing to shed light on tumor cell behavior. The combination of electroanalytical and optical biosensing technologies integrated in a lab-on-a-chip allows for continuous, label-free, and noninvasive probing of dynamic cell-to-cell interactions between adherent and nonadherent cocultures, thus providing real-time insights into tumor cell responses under physiologically relevant conditions. While the study of adherent cocultures is important for the understanding and suppression of metastatic invasion, the analysis of tumor cell interactions with nonadherent immune cells plays a vital role in cancer immunotherapy research. For the first time, the direct cell-to-cell interactions of tumor cells with bead-activated primary T cells were continuously assessed using an effector cell to target a cell ratio of 10:1.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases.

PubMed

Oh, Soo Jin; Choi, Young Ki; Shin, Ok Sarah

2018-03-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. © Copyright: Yonsei University College of Medicine 2018.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases

PubMed Central

2018-01-01

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. PMID:29436184

Pathogen exploitation of an abscisic acid- and jasmonate-inducible MAPK phosphatase and its interception by Arabidopsis immunity.

PubMed

Mine, Akira; Berens, Matthias L; Nobori, Tatsuya; Anver, Shajahan; Fukumoto, Kaori; Winkelmüller, Thomas M; Takeda, Atsushi; Becker, Dieter; Tsuda, Kenichi

2017-07-11

Phytopathogens promote virulence by, for example, exploiting signaling pathways mediated by phytohormones such as abscisic acid (ABA) and jasmonate (JA). Some plants can counteract pathogen virulence by invoking a potent form of immunity called effector-triggered immunity (ETI). Here, we report that ABA and JA mediate inactivation of the immune-associated MAP kinases (MAPKs), MPK3 and MPK6, in Arabidopsis thaliana ABA induced expression of genes encoding the protein phosphatases 2C (PP2Cs), HAI1 , HAI2 , and HAI3 through ABF/AREB transcription factors. These three HAI PP2Cs interacted with MPK3 and MPK6 and were required for ABA-mediated MPK3/MPK6 inactivation and immune suppression. The bacterial pathogen Pseudomonas syringae pv. tomato ( Pto ) DC3000 activates ABA signaling and produces a JA-mimicking phytotoxin, coronatine (COR), that promotes virulence. We found that Pto DC3000 induces HAI1 through COR-mediated activation of MYC2, a master transcription factor in JA signaling. HAI1 dephosphorylated MPK3 and MPK6 in vitro and was necessary for COR-mediated suppression of MPK3/MPK6 activation and immunity. Intriguingly, upon ETI activation, A. thaliana plants overcame the HAI1-dependent virulence of COR by blocking JA signaling. Finally, we showed conservation of induction of HAI PP2Cs by ABA and JA in other Brassicaceae species. Taken together, these results suggest that ABA and JA signaling pathways, which are hijacked by the bacterial pathogen, converge on the HAI PP2Cs that suppress activation of the immune-associated MAPKs. Also, our data unveil interception of JA-signaling activation as a host counterstrategy against the bacterial suppression of MAPKs during ETI.

Effects of Simulated Microgravity on a Host-Pathogen System

NASA Technical Reports Server (NTRS)

Gilbert, Rachel; Lo, Rachel; Bhattacharya, Sharmila

2017-01-01

While it has been shown that decades of astronauts and cosmonauts can suffer from illnesses both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. However, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use a ground-based simulated microgravity environment to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to counteract immune dysfunction in future space exploration.

The role of nitric oxide in the interaction of Arabidopsis thaliana with the biotrophic fungi, Golovinomyces orontii and Erysiphe pisi

PubMed Central

Schlicht, Markus; Kombrink, Erich

2013-01-01

Powdery mildews are a diverse group of pathogenic fungi that can infect a large number of plant species, including many economically important crops. However, basic and applied research on these devastating diseases has been hampered by the obligate biotrophic lifestyle of the pathogens, which require living host cells for growth and reproduction, and lacking genetic and molecular tools for important host plants. The establishment of Arabidopsis thaliana as a host of different powdery mildew species allowed pursuing new strategies to study the molecular mechanisms governing these complex plant–pathogen interactions. Nitric oxide (NO) has emerged as an important signaling molecule in plants, which is produced upon infection and involved in activation of plant immune responses. However, the source and pathway of NO production and its precise function in the regulatory network of reactions leading to resistance is still unknown. We studied the response of Arabidopsis thaliana to infection with the adapted powdery mildew, Golovinomyces orontii (compatible interaction) and the non-adapted, Erysiphe pisi (incompatible interaction). We observed that NO accumulated rapidly and transiently at infection sites and we established a correlation between the resistance phenotype and the amount and timing of NO production. Arabidopsis mutants with defective immune response accumulated lower NO levels compared to wild type. Conversely, increased NO levels, generated by treatment with chemicals or expression of a NO-synthesizing enzyme, resulted in enhanced resistance, but only sustained NO production prevented excessive leaf colonization by the fungus, which was not achieved by a short NO burst although this reduced the initial penetration success. By contrast, lowered NO levels did not impair the ultimate resistance phenotype. Although our results suggest a function of NO in mediating plant immune responses, a direct impact on pathogen growth and development cannot be excluded. PMID:24058365

Mice with Reconstituted Human Immune System Components as a Tool to Study Immune Cell Interactions in EBV Infection.

PubMed

Heuts, Frank; Nagy, Noemi

2017-01-01

Recent developments in mouse models that harbor part of a human immune system have proved extremely valuable to study the in vivo immune response to human specific pathogens such as Epstein-Barr virus. Over the last decades, advances in immunodeficient mouse strains that can be used as recipients for human immune cells have greatly enhanced the use of these models. Here, we describe the generation of mice with reconstituted human immune system (HIS mice) using immunocompromised mice transplanted with human CD34 + hematopoietic stem cells. We will also describe how such mice, in which human immune cells are generated de novo, can be used to study EBV infection.

Immune and genetic gardening of the intestinal microbiome

PubMed Central

Jacobs, Jonathan P.; Braun, Jonathan

2014-01-01

The mucosal immune system – consisting of adaptive and innate immune cells as well as the epithelium – is profoundly influenced by its microbial environment. There is now growing evidence that the converse is also true, that the immune system shapes the composition of the intestinal microbiome. During conditions of health, this bidirectional interaction achieves a homeostasis in which inappropriate immune responses to nonpathogenic microbes are averted and immune activity suppresses blooms of potentially pathogenic microbes (pathobionts). Genetic alteration in immune/epithelial function can affect host gardening of the intestinal microbiome, contributing to the diversity of intestinal microbiota within a population and in some cases allowing for unfavorable microbial ecologies (dysbiosis) that confer disease susceptibility. PMID:24613921

Rapid Expansion of Immune-Related Gene Families in the House Fly, Musca domestica

PubMed Central

Lazzaro, Brian P.; Clark, Andrew G.

2017-01-01

Abstract The house fly, Musca domestica, occupies an unusual diversity of potentially septic niches compared with other sequenced Dipteran insects and is a vector of numerous diseases of humans and livestock. In the present study, we apply whole-transcriptome sequencing to identify genes whose expression is regulated in adult flies upon bacterial infection. We then combine the transcriptomic data with analysis of rates of gene duplication and loss to provide insight into the evolutionary dynamics of immune-related genes. Genes up-regulated after bacterial infection are biased toward being evolutionarily recent innovations, suggesting the recruitment of novel immune components in the M. domestica or ancestral Dipteran lineages. In addition, using new models of gene family evolution, we show that several different classes of immune-related genes, particularly those involved in either pathogen recognition or pathogen killing, are duplicating at a significantly accelerated rate on the M. domestica lineage relative to other Dipterans. Taken together, these results suggest that the M. domestica immune response includes an elevated diversity of genes, perhaps as a consequence of its lifestyle in septic environments. PMID:28087775

Plant Immune Responses Against Viruses: How Does a Virus Cause Disease?[OA

PubMed Central

Mandadi, Kranthi K.; Scholthof, Karen-Beth G.

2013-01-01

Plants respond to pathogens using elaborate networks of genetic interactions. Recently, significant progress has been made in understanding RNA silencing and how viruses counter this apparently ubiquitous antiviral defense. In addition, plants also induce hypersensitive and systemic acquired resistance responses, which together limit the virus to infected cells and impart resistance to the noninfected tissues. Molecular processes such as the ubiquitin proteasome system and DNA methylation are also critical to antiviral defenses. Here, we provide a summary and update of advances in plant antiviral immune responses, beyond RNA silencing mechanisms—advances that went relatively unnoticed in the realm of RNA silencing and nonviral immune responses. We also document the rise of Brachypodium and Setaria species as model grasses to study antiviral responses in Poaceae, aspects that have been relatively understudied, despite grasses being the primary source of our calories, as well as animal feed, forage, recreation, and biofuel needs in the 21st century. Finally, we outline critical gaps, future prospects, and considerations central to studying plant antiviral immunity. To promote an integrated model of plant immunity, we discuss analogous viral and nonviral immune concepts and propose working definitions of viral effectors, effector-triggered immunity, and viral pathogen-triggered immunity. PMID:23709626

Porcine circovirus type 2 (PCV2): pathogenesis and interaction with the immune system.

PubMed

Meng, Xiang-Jin

2013-01-01

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated disease (PCVAD). The virus preferentially targets the lymphoid tissues, which leads to lymphoid depletion and immunosuppression in pigs. The disease is exacerbated by immunostimulation or concurrent infections with other pathogens. PCV2 resides in certain immune cells, such as macrophage and dendritic cells, and modulates their functions. Upregulation of IL-10 and proinflammatory cytokines in infected pigs may contribute to pathogenesis. Pig genetics influence host susceptibility to PCV2, but the viral genetic determinants for virulence remain unknown. PCV2 DNA and proteins interact with various cellular genes that control immune responses to regulate virus replication and pathogenesis. Both neutralizing antibodies and cell-mediated immunity are important immunological correlates of protection. Despite the availability of effective vaccines, variant strains of PCV2 continue to emerge. Although tremendous progress has been made toward understanding PCV2 pathogenesis and immune interactions, many important questions remain.

Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin and Toll-like receptor 5.

PubMed

Rumbo, Martin; Nempont, Clément; Kraehenbuhl, Jean-Pierre; Sirard, Jean-Claude

2006-05-22

Toll-like receptors (TLR) detect pathogen-associated molecular patterns (PAMP) and play a crucial role in triggering immunity. Due to their large surfaces in direct contact with the environment, mucosal tissues are the major sites of PAMP-TLR signalling. How innate and adaptive immunity are triggered through flagellin-TLR5 interaction is the main focus of the review. In view of recent reports on genetic polymorphism, we will summarize the impact of TLR5 on the susceptibility to mucosal infections and on various immuno-pathologies. Finally, the contribution of TLRs in the induction and maintenance of mucosal homeostasis and commensal discrimination is discussed.

Cytoplastic Glyceraldehyde-3-Phosphate Dehydrogenases Interact with ATG3 to Negatively Regulate Autophagy and Immunity in Nicotiana benthamiana

PubMed Central

Han, Shaojie; Wang, Yan; Zheng, Xiyin; Jia, Qi; Zhao, Jinping; Bai, Fan; Hong, Yiguo; Liu, Yule

2015-01-01

Autophagy as a conserved catabolic pathway can respond to reactive oxygen species (ROS) and plays an important role in degrading oxidized proteins in plants under various stress conditions. However, how ROS regulates autophagy in response to oxidative stresses is largely unknown. Here, we show that autophagy-related protein 3 (ATG3) interacts with the cytosolic glyceraldehyde-3-phosphate dehydrogenases (GAPCs) to regulate autophagy in Nicotiana benthamiana plants. We found that oxidative stress inhibits the interaction of ATG3 with GAPCs. Silencing of GAPCs significantly activates ATG3-dependent autophagy, while overexpression of GAPCs suppresses autophagy in N. benthamiana plants. Moreover, silencing of GAPCs enhances N gene-mediated cell death and plant resistance against both incompatible pathogens Tobacco mosaic virus and Pseudomonas syringae pv tomato DC3000, as well as compatible pathogen P. syringae pv tabaci. These results indicate that GAPCs have multiple functions in the regulation of autophagy, hypersensitive response, and plant innate immunity. PMID:25829441

Use of OmpU porins for attachment and invasion of Crassostrea gigas immune cells by the oyster pathogen Vibrio splendidus

PubMed Central

Duperthuy, Marylise; Schmitt, Paulina; Garzón, Edwin; Caro, Audrey; Rosa, Rafael D.; Le Roux, Frédérique; Lautrédou-Audouy, Nicole; Got, Patrice; Romestand, Bernard; de Lorgeril, Julien; Kieffer-Jaquinod, Sylvie; Bachère, Evelyne; Destoumieux-Garzón, Delphine

2011-01-01

OmpU porins are increasingly recognized as key determinants of pathogenic host Vibrio interactions. Although mechanisms remain incompletely understood, various species, including the human pathogen Vibrio cholera, require OmpU for host colonization and virulence. We have shown previously that OmpU is essential for virulence in the oyster pathogen Vibrio splendidus LGP32. Here, we showed that V. splendidus LGP32 invades the oyster immune cells, the hemocytes, through subversion of host-cell actin cytoskeleton. In this process, OmpU serves as an adhesin/invasin required for β-integrin recognition and host cell invasion. Furthermore, the major protein of oyster plasma, the extracellular superoxide dismutase Cg-EcSOD, is used as an opsonin mediating the OmpU-promoted phagocytosis through its RGD sequence. Finally, the endocytosed bacteria were found to survive intracellularly, evading the host defense by preventing acidic vacuole formation and limiting reactive oxygen species production. We conclude that (i) V. splendidus is a facultative intracellular pathogen that manipulates host defense mechanisms to enter and survive in host immune cells, and (ii) that OmpU is a major determinant of host cell invasion in Vibrio species, used by V. splendidus LGP32 to attach and invade oyster hemocytes through opsonisation by the oyster plasma Cg-EcSOD. PMID:21282662

Conversations between kingdoms: small RNAs.

PubMed

Weiberg, Arne; Bellinger, Marschal; Jin, Hailing

2015-04-01

Humans, animals, and plants are constantly under attack from pathogens and pests, resulting in severe consequences on global human health and crop production. Small RNA (sRNA)-mediated RNA interference (RNAi) is a conserved regulatory mechanism that is involved in almost all eukaryotic cellular processes, including host immunity and pathogen virulence. Recent evidence supports the significant contribution of sRNAs and RNAi to the communication between hosts and some eukaryotic pathogens, pests, parasites, or symbiotic microorganisms. Mobile silencing signals—most likely sRNAs—are capable of translocating from the host to its interacting organism, and vice versa. In this review, we will provide an overview of sRNA communications between different kingdoms, with a primary focus on the advances in plant-pathogen interaction systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

An E3 Ubiquitin Ligase-BAG Protein Module Controls Plant Innate Immunity and Broad-Spectrum Disease Resistance.

PubMed

You, Quanyuan; Zhai, Keran; Yang, Donglei; Yang, Weibing; Wu, Jingni; Liu, Junzhong; Pan, Wenbo; Wang, Jianjun; Zhu, Xudong; Jian, Yikun; Liu, Jiyun; Zhang, Yingying; Deng, Yiwen; Li, Qun; Lou, Yonggen; Xie, Qi; He, Zuhua

2016-12-14

Programmed cell death (PCD) and immunity in plants are tightly controlled to promote antimicrobial defense while preventing autoimmunity. However, the mechanisms contributing to this immune homeostasis are poorly understood. Here, we isolated a rice mutant ebr1 (enhanced blight and blast resistance 1) that shows enhanced broad-spectrum bacterial and fungal disease resistance, but displays spontaneous PCD, autoimmunity, and stunted growth. EBR1 encodes an E3 ubiquitin ligase that interacts with OsBAG4, which belongs to the BAG (Bcl-2-associated athanogene) family that functions in cell death, growth arrest, and immune responses in mammals. EBR1 directly targets OsBAG4 for ubiquitination-mediated degradation. Elevated levels of OsBAG4 in rice are necessary and sufficient to trigger PCD and enhanced disease resistance to pathogenic infection, most likely by activating pathogen-associated molecular patterns-triggered immunity (PTI). Together, our study suggests that an E3-BAG module orchestrates innate immune homeostasis and coordinates the trade-off between defense and growth in plants. Copyright © 2016 Elsevier Inc. All rights reserved.

Immune Recognition of Fungal Polysaccharides.

PubMed

Snarr, Brendan D; Qureshi, Salman T; Sheppard, Donald C

2017-08-28

The incidence of fungal infections has dramatically increased in recent years, in large part due to increased use of immunosuppressive medications, as well as aggressive medical and surgical interventions that compromise natural skin and mucosal barriers. There are relatively few currently licensed antifungal drugs, and rising resistance to these agents has led to interest in the development of novel preventative and therapeutic strategies targeting these devastating infections. One approach to combat fungal infections is to augment the host immune response towards these organisms. The polysaccharide-rich cell wall is the initial point of contact between fungi and the host immune system, and therefore, represents an important target for immunotherapeutic approaches. This review highlights the advances made in our understanding of the mechanisms by which the immune system recognizes and interacts with exopolysaccharides produced by four of the most common fungal pathogens: Aspergillus fumigatus , Candida albicans , Cryptococcus neoformans , and Histoplasma capsulatum . Work to date suggests that inner cell wall polysaccharides that play an important structural role are the most conserved across diverse members of the fungal kingdom, and elicit the strongest innate immune responses. The immune system senses these carbohydrates through receptors, such as lectins and complement proteins. In contrast, a greater diversity of polysaccharides is found within the outer cell walls of pathogenic fungi. These glycans play an important role in immune evasion, and can even induce anti-inflammatory host responses. Further study of the complex interactions between the host immune system and the fungal polysaccharides will be necessary to develop more effective therapeutic strategies, as well as to explore the use of immunosuppressive polysaccharides as therapeutic agents to modulate inflammation.

Buried treasure: evolutionary perspectives on microbial iron piracy

PubMed Central

Barber, Matthew F.; Elde, Nels C.

2015-01-01

Host-pathogen interactions provide valuable systems for the study of evolutionary genetics and natural selection. The sequestration of essential iron has emerged as a critical innate defense system termed nutritional immunity, leading pathogens to evolve mechanisms of `iron piracy' to scavenge this metal from host proteins. This battle for iron carries numerous consequences not only for host-pathogen evolution, but also microbial community interactions. Here we highlight recent and potential future areas of investigation on the evolutionary implications of microbial iron piracy in relation to molecular arms races, host range, competition, and virulence. Applying evolutionary genetic approaches to the study of microbial iron acquisition could also provide new inroads for understanding and combating infectious disease. PMID:26431675

Microbial genome-enabled insights into plant-microorganism interactions.

PubMed

Guttman, David S; McHardy, Alice C; Schulze-Lefert, Paul

2014-12-01

Advances in genome-based studies on plant-associated microorganisms have transformed our understanding of many plant pathogens and are beginning to greatly widen our knowledge of plant interactions with mutualistic and commensal microorganisms. Pathogenomics has revealed how pathogenic microorganisms adapt to particular hosts, subvert innate immune responses and change host range, as well as how new pathogen species emerge. Similarly, culture-independent community profiling methods, coupled with metagenomic and metatranscriptomic studies, have provided the first insights into the emerging field of research on plant-associated microbial communities. Together, these approaches have the potential to bridge the gap between plant microbial ecology and plant pathology, which have traditionally been two distinct research fields.

Opportunistic respiratory pathogens in the oral cavity of the elderly.

PubMed

Tada, Akio; Hanada, Nobuhiro

2010-10-01

The oral cavity of the hospitalized or bedridden elderly is often a reservoir for opportunistic pathogens associated with respiratory diseases. Commensal flora and the host interact in a balanced fashion and oral infections are considered to appear following an imbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. The definition of the process involved in colonization by opportunistic respiratory pathogens needs to elucidate the factors responsible for the transition of the microbiota from commensal to pathogenic flora. The regulatory factors influencing the oral ecosystem can be divided into three major categories: the host defense system, commensal bacteria, and external pathogens. In this article, we review the profile of these categories including the intricate cellular interaction between immune factors and commensal bacteria and the disturbance in homeostasis in the oral cavity of hospitalized or bedridden elderly, which facilitates oral colonization by opportunistic respiratory pathogens. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Structure-informed insights for NLR functioning in plant immunity.

PubMed

Sukarta, Octavina C A; Slootweg, Erik J; Goverse, Aska

2016-08-01

To respond to foreign invaders, plants have evolved a cell autonomous multilayered immune system consisting of extra- and intracellular immune receptors. Nucleotide binding and oligomerization domain (NOD)-like receptors (NLRs) mediate recognition of pathogen effectors inside the cell and trigger a host specific defense response, often involving controlled cell death. NLRs consist of a central nucleotide-binding domain, which is flanked by an N-terminal CC or TIR domain and a C-terminal leucine-rich repeat domain (LRR). These multidomain proteins function as a molecular switch and their activity is tightly controlled by intra and inter-molecular interactions. In contrast to metazoan NLRs, the structural basis underlying NLR functioning as a pathogen sensor and activator of immune responses in plants is largely unknown. However, the first crystal structures of a number of plant NLR domains were recently obtained. In addition, biochemical and structure-informed analyses revealed novel insights in the cooperation between NLR domains and the formation of pre- and post activation complexes, including the coordinated activity of NLR pairs as pathogen sensor and executor of immune responses. Moreover, the discovery of novel integrated domains underscores the structural diversity of NLRs and provides alternative models for how these immune receptors function in plants. In this review, we will highlight these recent advances to provide novel insights in the structural, biochemical and molecular aspects involved in plant NLR functioning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Establishment of tumor-associated immunity requires interaction of Heat Shock Proteins with CD91

PubMed Central

Zhou, Yu Jerry; Messmer, Michelle Nicole; Binder, Robert Julian

2014-01-01

Host antitumor adaptive immune responses are generated as a result of the body’s immunosurveillance mechanisms. How the antitumor immune response is initially primed remains unclear, given that soluble tumor antigens generally are quantitatively insufficient for cross-priming and tumors lack the classical pathogen-associated molecular patterns (PAMPs) to activate costimulation and initiate cross-priming. We explored the interaction of the tumor-derived heat-shock proteins (HSP) with their common receptor (CD91) on antigen presenting cells (APCs) as a mechanism for host-priming of T cell-mediated antitumor immunity. Using targeted genetic disruption of the interaction between HSPs and CD19, we demonstrated that specific ablation of CD91 in APCs prevented the establishment of antitumor immunity. The antitumor immunity was also inhibited when the transfer of tumor-derived HSPs to APCs was prevented using an endogenous inhibitor of CD91. Inhibition was manifested in a reduction of cross-presentation of tumor-derived antigenic peptides in the lymph nodes providing a molecular basis for the observed immunity associated with tumor development. Our findings demonstrate that early in tumor development, the HSP-CD91 pathway is critical for the establishment of antitumor immunity. PMID:24778318

Immunity by equilibrium.

PubMed

Eberl, Gérard

2016-08-01

The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

A dityrosine network mediated by dual oxidase and peroxidase influences the persistence of Lyme disease pathogens within the vector.

PubMed

Yang, Xiuli; Smith, Alexis A; Williams, Mark S; Pal, Utpal

2014-05-02

Ixodes scapularis ticks transmit a wide array of human and animal pathogens including Borrelia burgdorferi; however, how tick immune components influence the persistence of invading pathogens remains unknown. As originally demonstrated in Caenorhabditis elegans and later in Anopheles gambiae, we show here that an acellular gut barrier, resulting from the tyrosine cross-linking of the extracellular matrix, also exists in I. scapularis ticks. This dityrosine network (DTN) is dependent upon a dual oxidase (Duox), which is a member of the NADPH oxidase family. The Ixodes genome encodes for a single Duox and at least 16 potential peroxidase proteins, one of which, annotated as ISCW017368, together with Duox has been found to be indispensible for DTN formation. This barrier influences pathogen survival in the gut, as an impaired DTN in Doux knockdown or in specific peroxidase knockdown ticks, results in reduced levels of B. burgdorferi persistence within ticks. Absence of a complete DTN formation in knockdown ticks leads to the activation of specific tick innate immune pathway genes that potentially resulted in the reduction of spirochete levels. Together, these results highlighted the evolution of the DTN in a diverse set of arthropod vectors, including ticks, and its role in protecting invading pathogens like B. burgdorferi. Further understanding of the molecular basis of tick innate immune responses, vector-pathogen interaction, and their contributions in microbial persistence may help the development of new targets for disrupting the pathogen life cycle.

Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis.

PubMed

Seal, John B; Alverdy, John C; Zaborina, Olga; An, Gary

2011-09-19

There is a growing realization that alterations in host-pathogen interactions (HPI) can generate disease phenotypes without pathogen invasion. The gut represents a prime region where such HPI can arise and manifest. Under normal conditions intestinal microbial communities maintain a stable, mutually beneficial ecosystem. However, host stress can lead to changes in environmental conditions that shift the nature of the host-microbe dialogue, resulting in escalation of virulence expression, immune activation and ultimately systemic disease. Effective modulation of these dynamics requires the ability to characterize the complexity of the HPI, and dynamic computational modeling can aid in this task. Agent-based modeling is a computational method that is suited to representing spatially diverse, dynamical systems. We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis. An agent-based model (ABM) of virulence regulation in Pseudomonas aeruginosa was developed by translating bacterial and host cell sense-and-response mechanisms into behavioral rules for computational agents and integrated into a virtual environment representing the host-microbe interface in the gut. The resulting gut milieu ABM (GMABM) was used to: 1) investigate a potential clinically relevant laboratory experimental condition not yet developed--i.e. non-lethal transient segmental intestinal ischemia, 2) examine the sufficiency of existing hypotheses to explain experimental data--i.e. lethality in a model of major surgical insult and stress, and 3) produce behavior to potentially guide future experimental design--i.e. suggested sample points for a potential laboratory model of non-lethal transient intestinal ischemia. Furthermore, hypotheses were generated to explain certain discrepancies between the behaviors of the GMABM and biological experiments, and new investigatory avenues proposed to test those hypotheses. Agent-based modeling can account for the spatio-temporal dynamics of an HPI, and, even when carried out with a relatively high degree of abstraction, can be useful in the investigation of system-level consequences of putative mechanisms operating at the individual agent level. We suggest that an integrated and iterative heuristic relationship between computational modeling and more traditional laboratory and clinical investigations, with a focus on identifying useful and sufficient degrees of abstraction, will enhance the efficiency and translational productivity of biomedical research.

Agent-based dynamic knowledge representation of Pseudomonas aeruginosa virulence activation in the stressed gut: Towards characterizing host-pathogen interactions in gut-derived sepsis

PubMed Central

2011-01-01

Background There is a growing realization that alterations in host-pathogen interactions (HPI) can generate disease phenotypes without pathogen invasion. The gut represents a prime region where such HPI can arise and manifest. Under normal conditions intestinal microbial communities maintain a stable, mutually beneficial ecosystem. However, host stress can lead to changes in environmental conditions that shift the nature of the host-microbe dialogue, resulting in escalation of virulence expression, immune activation and ultimately systemic disease. Effective modulation of these dynamics requires the ability to characterize the complexity of the HPI, and dynamic computational modeling can aid in this task. Agent-based modeling is a computational method that is suited to representing spatially diverse, dynamical systems. We propose that dynamic knowledge representation of gut HPI with agent-based modeling will aid in the investigation of the pathogenesis of gut-derived sepsis. Methodology/Principal Findings An agent-based model (ABM) of virulence regulation in Pseudomonas aeruginosa was developed by translating bacterial and host cell sense-and-response mechanisms into behavioral rules for computational agents and integrated into a virtual environment representing the host-microbe interface in the gut. The resulting gut milieu ABM (GMABM) was used to: 1) investigate a potential clinically relevant laboratory experimental condition not yet developed - i.e. non-lethal transient segmental intestinal ischemia, 2) examine the sufficiency of existing hypotheses to explain experimental data - i.e. lethality in a model of major surgical insult and stress, and 3) produce behavior to potentially guide future experimental design - i.e. suggested sample points for a potential laboratory model of non-lethal transient intestinal ischemia. Furthermore, hypotheses were generated to explain certain discrepancies between the behaviors of the GMABM and biological experiments, and new investigatory avenues proposed to test those hypotheses. Conclusions/Significance Agent-based modeling can account for the spatio-temporal dynamics of an HPI, and, even when carried out with a relatively high degree of abstraction, can be useful in the investigation of system-level consequences of putative mechanisms operating at the individual agent level. We suggest that an integrated and iterative heuristic relationship between computational modeling and more traditional laboratory and clinical investigations, with a focus on identifying useful and sufficient degrees of abstraction, will enhance the efficiency and translational productivity of biomedical research. PMID:21929759

Immunoglobulin G1 Fc domain motions: implications for Fc engineering

PubMed Central

Frank, Martin; Walker, Ross C.; Lanzilotta, William N.; Prestegard, James H.; Barb, Adam W.

2014-01-01

The fragment crystallizable (Fc) region links the key pathogen identification and destruction properties of immunoglobulin G(IgG). Pathogen opsonization positions Fcs to activate pro-inflammatory Fcγ receptors (FcγRs) on immune cells. The cellular response and committal to a damaging, though protective, immune response is tightly controlled at multiple levels. Control mechanisms are diverse and in many cases unclear, but one frequently suggested contribution originates in Fcγ receptor affinity being modulated through shifts in Fc conformational sampling. Here we report a previously unseen IgG1 Fc conformation. This observation motivated an extensive molecular dynamics (MD) investigation of polypeptide and glycan motions that revealed greater amplitude of motion for the N-terminal Cγ2 domains and N-glycan than previously observed. Residues in the Cγ2/Cγ3 interface and disulphide-bonded hinge were identified as influencing the Cγ2 motion. Our results are consistent with a model of Fc that is structurally dynamic. Conformational states that are competent to bind immune-stimulating FcγRs interconverted with Fc conformations distinct from those observed in FcγR complexes, which may represent a transient, nonbinding population. PMID:24522230

A Critical Role of Zinc Importer AdcABC in Group A Streptococcus-Host Interactions During Infection and Its Implications for Vaccine Development.

PubMed

Makthal, Nishanth; Nguyen, Kimberly; Do, Hackwon; Gavagan, Maire; Chandrangsu, Pete; Helmann, John D; Olsen, Randall J; Kumaraswami, Muthiah

2017-07-01

Bacterial pathogens must overcome host immune mechanisms to acquire micronutrients for successful replication and infection. Streptococcus pyogenes, also known as group A streptococcus (GAS), is a human pathogen that causes a variety of clinical manifestations, and disease prevention is hampered by lack of a human GAS vaccine. Herein, we report that the mammalian host recruits calprotectin (CP) to GAS infection sites and retards bacterial growth by zinc limitation. However, a GAS-encoded zinc importer and a nuanced zinc sensor aid bacterial defense against CP-mediated growth inhibition and contribute to GAS virulence. Immunization of mice with the extracellular component of the zinc importer confers protection against systemic GAS challenge. Together, we identified a key early stage host-GAS interaction and translated that knowledge into a novel vaccine strategy against GAS infection. Furthermore, we provided evidence that a similar struggle for zinc may occur during other streptococcal infections, which raises the possibility of a broad-spectrum prophylactic strategy against multiple streptococcal pathogens. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Mechanisms of Disease: Host-Pathogen Interactions between Burkholderia Species and Lung Epithelial Cells

PubMed Central

David, Jonathan; Bell, Rachel E.; Clark, Graeme C.

2015-01-01

Members of the Burkholderia species can cause a range of severe, often fatal, respiratory diseases. A variety of in vitro models of infection have been developed in an attempt to elucidate the mechanism by which Burkholderia spp. gain entry to and interact with the body. The majority of studies have tended to focus on the interaction of bacteria with phagocytic cells with a paucity of information available with regard to the lung epithelium. However, the lung epithelium is becoming more widely recognized as an important player in innate immunity and the early response to infections. Here we review the complex relationship between Burkholderia species and epithelial cells with an emphasis on the most pathogenic species, Burkholderia pseudomallei and Burkholderia mallei. The current gaps in knowledge in our understanding are highlighted along with the epithelial host-pathogen interactions that offer potential opportunities for therapeutic intervention. PMID:26636042

Interactions of the Intestinal Epithelium with the Pathogen and the Indigenous Microbiota: A Three-Way Crosstalk

PubMed Central

Srikanth, C. V.; McCormick, Beth A.

2008-01-01

The mucosal surfaces of the gastrointestinal tract harbor a vast number of commensal microbiota that have coevolved with the host, and in addition display one of the most complex relationships with the host. This relationship affects several important aspects of the biology of the host including the synthesis of nutrients, protection against infection, and the development of the immune system. On the other hand, despite the existence of several lines of mucosal defense mechanisms, pathogenic organisms such as Shigella and Salmonella have evolved sophisticated virulence strategies for breaching these barriers. The constant challenge from these pathogens and the attempts by the host to counter them set up a dynamic equilibrium of cellular and molecular crosstalk. Even slight perturbations in this equilibrium may be detrimental to the host leading to severe bacterial infection or even autoimmune diseases like inflammatory bowel disease. Several experimental model systems, including germ-free mice and antibiotic-treated mice, have been used by various researchers to study this complex relationship. Although it is only the beginning, it promises to be an exciting era in the study of these host-microbe relationships. PMID:19259328

Vaccine Adjuvants: from 1920 to 2015 and Beyond

PubMed Central

Di Pasquale, Alberta; Preiss, Scott; Tavares Da Silva, Fernanda; Garçon, Nathalie

2015-01-01

The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190

Glycoconjugates in Host-Helminth Interactions

PubMed Central

Prasanphanich, Nina Salinger; Mickum, Megan L.; Heimburg-Molinaro, Jamie; Cummings, Richard D.

2013-01-01

Helminths are multicellular parasitic worms that comprise a major class of human pathogens and cause an immense amount of suffering worldwide. Helminths possess an abundance of complex and unique glycoconjugates that interact with both the innate and adaptive arms of immunity in definitive and intermediate hosts. These glycoconjugates represent a major untapped reservoir of immunomodulatory compounds, which have the potential to treat autoimmune and inflammatory disorders, and antigenic glycans, which could be exploited as vaccines and diagnostics. This review will survey current knowledge of the interactions between helminth glycans and host immunity and highlight the gaps in our understanding which are relevant to advancing therapeutics, vaccine development, and diagnostics. PMID:24009607

Pathogen recognition in the innate immune response.

PubMed

Kumar, Himanshu; Kawai, Taro; Akira, Shizuo

2009-04-28

Immunity against microbial pathogens primarily depends on the recognition of pathogen components by innate receptors expressed on immune and non-immune cells. Innate receptors are evolutionarily conserved germ-line-encoded proteins and include TLRs (Toll-like receptors), RLRs [RIG-I (retinoic acid-inducible gene-I)-like receptors] and NLRs (Nod-like receptors). These receptors recognize pathogens or pathogen-derived products in different cellular compartments, such as the plasma membrane, the endosomes or the cytoplasm, and induce the expression of cytokines, chemokines and co-stimulatory molecules to eliminate pathogens and instruct pathogen-specific adaptive immune responses. In the present review, we will discuss the recent progress in the study of pathogen recognition by TLRs, RLRs and NLRs and their signalling pathways.

Modeling the dynamical interaction between epidemics on overlay networks

NASA Astrophysics Data System (ADS)

Marceau, Vincent; Noël, Pierre-André; Hébert-Dufresne, Laurent; Allard, Antoine; Dubé, Louis J.

2011-08-01

Epidemics seldom occur as isolated phenomena. Typically, two or more viral agents spread within the same host population and may interact dynamically with each other. We present a general model where two viral agents interact via an immunity mechanism as they propagate simultaneously on two networks connecting the same set of nodes. By exploiting a correspondence between the propagation dynamics and a dynamical process performing progressive network generation, we develop an analytical approach that accurately captures the dynamical interaction between epidemics on overlay networks. The formalism allows for overlay networks with arbitrary joint degree distribution and overlap. To illustrate the versatility of our approach, we consider a hypothetical delayed intervention scenario in which an immunizing agent is disseminated in a host population to hinder the propagation of an undesirable agent (e.g., the spread of preventive information in the context of an emerging infectious disease).

Themes from variation: probing the commonalities of symbiotic associations.

PubMed

Saffo, Mary Beth

2002-04-01

Research on symbiosis (including antagonistic and mutualistic associations) wrestles, directly or indirectly, with the paradox: why are symbiotic associations so prevalent in the biosphere in the face of ubiquitous immune or antibiotic defenses among organisms? The symposium "Living Together: the Dynamics of Symbiotic Interactions" considered several questions: 1. How do symbiotic species partners come together? Do symbioses share similar patterns of signal recognition and response? 2. What roles do nutrients and metabolites play in symbiotic interactions, and how are metabolic exchanges affected by environmental changes? 3. In what ways do the dynamics of multispecies symbioses differ from two-species associations? 4. How do antagonistic (parasitic, pathogenic) symbioses differ from mutualistic ones? In what ways do changes in the biotic and physical environment affect the evolutionary balance of symbiotic associations? 5. What are the coevolutionary patterns of symbiotic associations? 6. Which research techniques, and strategies of experimental design, might be useful across a broad range of symbiotic associations?Two themes emerged from the symposium. First, all the participants have incorporated multiple techniques and perspectives into their work, approaches which facilitate the understanding of symbiotic dynamics at several levels of biological organization. Secondly, many of the papers addressed genetic and environmental variation in symbiotic interactions. Such approaches are useful tools for analysis of the mechanics of interspecies interactions and for characterization of the most important factors which influence them. They provide us with the tools to evaluate symbioses in a world of complexity, variation and change.

Interactions between Autophagy and Inhibitory Cytokines

PubMed Central

Wu, Tian-tian; Li, Wei-Min; Yao, Yong-Ming

2016-01-01

Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy. PMID:27313501

Host-pathogen interactions between the human innate immune system and Candida albicans—understanding and modeling defense and evasion strategies

PubMed Central

Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F.; Dandekar, Thomas; Schuster, Stefan

2015-01-01

The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. PMID:26175718

Tunneling Nanotubes: Intimate Communication between Myeloid Cells.

PubMed

Dupont, Maeva; Souriant, Shanti; Lugo-Villarino, Geanncarlo; Maridonneau-Parini, Isabelle; Vérollet, Christel

2018-01-01

Tunneling nanotubes (TNT) are dynamic connections between cells, which represent a novel route for cell-to-cell communication. A growing body of evidence points TNT towards a role for intercellular exchanges of signals, molecules, organelles, and pathogens, involving them in a diverse array of functions. TNT form among several cell types, including neuronal cells, epithelial cells, and almost all immune cells. In myeloid cells (e.g., macrophages, dendritic cells, and osteoclasts), intercellular communication via TNT contributes to their differentiation and immune functions. Importantly, TNT enable myeloid cells to communicate with a targeted neighboring or distant cell, as well as with other cell types, therefore creating a complex variety of cellular exchanges. TNT also contribute to pathogen spread as they serve as "corridors" from a cell to another. Herein, we addressed the complexity of the definition and in vitro characterization of TNT in innate immune cells, the different processes involved in their formation, and their relevance in vivo . We also assess our current understanding of how TNT participate in immune surveillance and the spread of pathogens, with a particular interest for HIV-1. Overall, despite recent progress in this growing research field, we highlight that further investigation is needed to better unveil the role of TNT in both physiological and pathological conditions.

Perception of pathogenic or beneficial bacteria and their evasion of host immunity: pattern recognition receptors in the frontline

PubMed Central

Trdá, Lucie; Boutrot, Freddy; Claverie, Justine; Brulé, Daphnée; Dorey, Stephan; Poinssot, Benoit

2015-01-01

Plants are continuously monitoring the presence of microorganisms to establish an adapted response. Plants commonly use pattern recognition receptors (PRRs) to perceive microbe- or pathogen-associated molecular patterns (MAMPs/PAMPs) which are microorganism molecular signatures. Located at the plant plasma membrane, the PRRs are generally receptor-like kinases (RLKs) or receptor-like proteins (RLPs). MAMP detection will lead to the establishment of a plant defense program called MAMP-triggered immunity (MTI). In this review, we overview the RLKs and RLPs that assure early recognition and control of pathogenic or beneficial bacteria. We also highlight the crucial function of PRRs during plant-microbe interactions, with a special emphasis on the receptors of the bacterial flagellin and peptidoglycan. In addition, we discuss the multiple strategies used by bacteria to evade PRR-mediated recognition. PMID:25904927

Using process algebra to develop predator-prey models of within-host parasite dynamics.

PubMed

McCaig, Chris; Fenton, Andy; Graham, Andrea; Shankland, Carron; Norman, Rachel

2013-07-21

As a first approximation of immune-mediated within-host parasite dynamics we can consider the immune response as a predator, with the parasite as its prey. In the ecological literature of predator-prey interactions there are a number of different functional responses used to describe how a predator reproduces in response to consuming prey. Until recently most of the models of the immune system that have taken a predator-prey approach have used simple mass action dynamics to capture the interaction between the immune response and the parasite. More recently Fenton and Perkins (2010) employed three of the most commonly used prey-dependent functional response terms from the ecological literature. In this paper we make use of a technique from computing science, process algebra, to develop mathematical models. The novelty of the process algebra approach is to allow stochastic models of the population (parasite and immune cells) to be developed from rules of individual cell behaviour. By using this approach in which individual cellular behaviour is captured we have derived a ratio-dependent response similar to that seen in the previous models of immune-mediated parasite dynamics, confirming that, whilst this type of term is controversial in ecological predator-prey models, it is appropriate for models of the immune system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir–Host Populations

PubMed Central

Plowright, Raina K.; Peel, Alison J.; Streicker, Daniel G.; Gilbert, Amy T.; McCallum, Hamish; Wood, James; Baker, Michelle L.; Restif, Olivier

2016-01-01

Progress in combatting zoonoses that emerge from wildlife is often constrained by limited knowledge of the biology of pathogens within reservoir hosts. We focus on the host–pathogen dynamics of four emerging viruses associated with bats: Hendra, Nipah, Ebola, and Marburg viruses. Spillover of bat infections to humans and domestic animals often coincides with pulses of viral excretion within bat populations, but the mechanisms driving such pulses are unclear. Three hypotheses dominate current research on these emerging bat infections. First, pulses of viral excretion could reflect seasonal epidemic cycles driven by natural variations in population densities and contact rates among hosts. If lifelong immunity follows recovery, viruses may disappear locally but persist globally through migration; in either case, new outbreaks occur once births replenish the susceptible pool. Second, epidemic cycles could be the result of waning immunity within bats, allowing local circulation of viruses through oscillating herd immunity. Third, pulses could be generated by episodic shedding from persistently infected bats through a combination of physiological and ecological factors. The three scenarios can yield similar patterns in epidemiological surveys, but strategies to predict or manage spillover risk resulting from each scenario will be different. We outline an agenda for research on viruses emerging from bats that would allow for differentiation among the scenarios and inform development of evidence-based interventions to limit threats to human and animal health. These concepts and methods are applicable to a wide range of pathogens that affect humans, domestic animals, and wildlife. PMID:27489944

Laboratory simulation reveals significant impacts of ocean acidification on microbial community composition and host-pathogen interactions between the blood clam and Vibrio harveyi.

PubMed

Zha, Shanjie; Liu, Saixi; Su, Wenhao; Shi, Wei; Xiao, Guoqiang; Yan, Maocang; Liu, Guangxu

2017-12-01

It has been suggested that climate change may promote the outbreaks of diseases in the sea through altering the host susceptibility, the pathogen virulence, and the host-pathogen interaction. However, the impacts of ocean acidification (OA) on the pathogen components of bacterial community and the host-pathogen interaction of marine bivalves are still poorly understood. Therefore, 16S rRNA high-throughput sequencing and host-pathogen interaction analysis between blood clam (Tegillarca granosa) and Vibrio harveyi were conducted in the present study to gain a better understanding of the ecological impacts of ocean acidification. The results obtained revealed a significant impact of ocean acidification on the composition of microbial community at laboratory scale. Notably, the abundance of Vibrio, a major group of pathogens to many marine organisms, was significantly increased under ocean acidification condition. In addition, the survival rate and haemolytic activity of V. harveyi were significantly higher in the presence of haemolymph of OA treated T. granosa, indicating a compromised immunity of the clam and enhanced virulence of V. harveyi under future ocean acidification scenarios. Conclusively, the results obtained in this study suggest that future ocean acidification may increase the risk of Vibrio pathogen infection for marine bivalve species, such as blood clams. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Anopheles innate immune system in the defense against malaria infection

PubMed Central

Clayton, April M.; Dong, Yuemei; Dimopoulos, George

2014-01-01

The multifaceted innate immune system of insects is capable of fighting infection by a variety of pathogens including those causing human malaria. Malaria transmission by the Anopheles mosquito depends on the Plasmodium parasite’s successful completion of its lifecycle in the insect vector, a process that involves interactions with several tissues and cell types as well as with the mosquito’s innate immune system. This review will discuss our current understanding of the Anopheles mosquito’s innate immune responses against the malaria parasite Plasmodium and the influence of the insect’s intestinal microbiota on parasite infection. PMID:23988482

Adaptive Immunity to Cryptococcus neoformans Infections

PubMed Central

Mukaremera, Liliane; Nielsen, Kirsten

2017-01-01

The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of fungal pathogens with different phenotypic and genotypic diversity that cause disease in immunocompromised patients as well as in healthy individuals. The immune response resulting from the interaction between Cryptococcus and the host immune system is a key determinant of the disease outcome. The species C. neoformans causes the majority of human infections, and therefore almost all immunological studies focused on C. neoformans infections. Thus, this review presents current understanding on the role of adaptive immunity during C. neoformans infections both in humans and in animal models of disease. PMID:29333430

Temporal dynamics, diversity, and interplay in three components of the virodiversity of a Mallard population: influenza A virus, avian paramyxovirus and avian coronavirus.

PubMed

Wille, Michelle; Avril, Alexis; Tolf, Conny; Schager, Anna; Larsson, Sara; Borg, Olivia; Olsen, Björn; Waldenström, Jonas

2015-01-01

Multiple infections, or simultaneous infection of a host with multiple parasites, are the rule rather than the exception. Interactions between co-occurring pathogens in a population may be mutualistic, competitive or facilitative. For some pathogen combinations, these interrelated effects will have epidemiological consequences; however this is as yet poorly incorporated into practical disease ecology. For example, screening of Mallards for influenza A viruses (IAV) have repeatedly revealed high prevalence and large subtype diversity in the Northern Hemisphere. Other studies have identified avian paramyxovirus type 1 (APMV-1) and coronaviruses (CoVs) in Mallards, but without making inferences on the larger viral assemblage. In this study we followed 144 wild Mallards across an autumn season in a natural stopover site and constructed infection histories of IAV, APMV-1 and CoV. There was a high prevalence of IAV, comprising of 27 subtype combinations, while APMV-1 had a comparatively low prevalence (with a peak of 2%) and limited strain variation, similar to previous findings. Avian CoVs were common, with prevalence up to 12%, and sequence analysis identified different putative genetic lineages. An investigation of the dynamics of co-infections revealed a synergistic effect between CoV and IAV, whereby CoV prevalence was higher given that the birds were co-infected with IAV. There were no interactive effects between IAV and APMV-1. Disease dynamics are the result of an interplay between parasites, host immune responses, and resources; and is imperative that we begin to include all factors to better understand infectious disease risk. Copyright © 2014 Elsevier B.V. All rights reserved.

The role of TGF-β signaling and apoptosis in innate and adaptive immunity in zebrafish: a systems biology approach.

PubMed

Lin, Che; Lin, Chin-Nan; Wang, Yu-Chao; Liu, Fang-Yu; Chuang, Yung-Jen; Lan, Chung-Yu; Hsieh, Wen-Ping; Chen, Bor-Sen

2014-10-24

The immune system is a key biological system present in vertebrates. Exposure to pathogens elicits various defensive immune mechanisms that protect the host from potential threats and harmful substances derived from pathogens such as parasites, bacteria, and viruses. The complex immune system of humans and many other vertebrates can be divided into two major categories: the innate and the adaptive immune systems. At present, analysis of the complex interactions between the two subsystems that regulate host defense and inflammatory responses remains challenging. Based on time-course microarray data following primary and secondary infection of zebrafish by Candida albicans, we constructed two intracellular protein-protein interaction (PPI) networks for primary and secondary responses of the host. 57 proteins and 341 PPIs were identified for primary infection while 90 proteins and 385 PPIs were identified for secondary infection. There were 20 proteins in common while 37 and 70 proteins specific to primary and secondary infection. By inspecting the hub proteins of each network and comparing significant changes in the number of linkages between the two PPI networks, we identified TGF-β signaling and apoptosis as two of the main functional modules involved in primary and secondary infection. Our initial in silico analyses pave the way for further investigation into the interesting roles played by the TGF-β signaling pathway and apoptosis in innate and adaptive immunity in zebrafish. Such insights could lead to therapeutic advances and improved drug design in the continual battle against infectious diseases.

Plant-Associated Symbiotic Burkholderia Species Lack Hallmark Strategies Required in Mammalian Pathogenesis

PubMed Central

Fong, Stephanie; Yerrapragada, Shailaja; Estrada-de los Santos, Paulina; Yang, Paul; Song, Nannie; Kano, Stephanie; de Faria, Sergio M.; Dakora, Felix D.; Weinstock, George; Hirsch, Ann M.

2014-01-01

Burkholderia is a diverse and dynamic genus, containing pathogenic species as well as species that form complex interactions with plants. Pathogenic strains, such as B. pseudomallei and B. mallei, can cause serious disease in mammals, while other Burkholderia strains are opportunistic pathogens, infecting humans or animals with a compromised immune system. Although some of the opportunistic Burkholderia pathogens are known to promote plant growth and even fix nitrogen, the risk of infection to infants, the elderly, and people who are immunocompromised has not only resulted in a restriction on their use, but has also limited the application of non-pathogenic, symbiotic species, several of which nodulate legume roots or have positive effects on plant growth. However, recent phylogenetic analyses have demonstrated that Burkholderia species separate into distinct lineages, suggesting the possibility for safe use of certain symbiotic species in agricultural contexts. A number of environmental strains that promote plant growth or degrade xenobiotics are also included in the symbiotic lineage. Many of these species have the potential to enhance agriculture in areas where fertilizers are not readily available and may serve in the future as inocula for crops growing in soils impacted by climate change. Here we address the pathogenic potential of several of the symbiotic Burkholderia strains using bioinformatics and functional tests. A series of infection experiments using Caenorhabditis elegans and HeLa cells, as well as genomic characterization of pathogenic loci, show that the risk of opportunistic infection by symbiotic strains such as B. tuberum is extremely low. PMID:24416172

A stochastic spatial model of HIV dynamics with an asymmetric battle between the virus and the immune system

NASA Astrophysics Data System (ADS)

Lin, Hai; Shuai, J. W.

2010-04-01

A stochastic spatial model based on the Monte Carlo approach is developed to study the dynamics of human immunodeficiency virus (HIV) infection. We aim to propose a more detailed and realistic simulation frame by incorporating many important features of HIV dynamics, which include infections, replications and mutations of viruses, antigen recognitions, activations and proliferations of lymphocytes, and diffusions, encounters and interactions of virions and lymphocytes. Our model successfully reproduces the three-phase pattern observed in HIV infection, and the simulation results for the time distribution from infection to AIDS onset are also in good agreement with the clinical data. The interactions of viruses and the immune system in all the three phases are investigated. We assess the relative importance of various immune system components in the acute phase. The dynamics of how the two important factors, namely the viral diversity and the asymmetric battle between HIV and the immune system, result in AIDS are investigated in detail with the model.

RHIM-based protein:protein interactions in anti-microbial defence against programmed cell death by necroptosis.

PubMed

Baker, Max O D G; Shanmugam, Nirukshan; Pham, Chi L L; Strange, Merryn; Steain, Megan; Sunde, Margaret

2018-05-05

The Receptor-interacting protein kinase Homotypic Interaction Motif (RHIM) is an amino acid sequence that mediates multiple protein:protein interactions in the mammalian programmed cell death pathway known as necroptosis. At least one key RHIM-based complex has been shown to have a functional amyloid fibril structure, which provides a stable hetero-oligomeric platform for downstream signaling. RHIMs and related motifs are present in immunity-related proteins across nature, from viruses to fungi to metazoans. Necroptosis is a hallmark feature of cellular clearance of infection. For this reason, numerous pathogens, including viruses and bacteria, have developed varied methods to modulate necroptosis, focusing on inhibiting RHIM:RHIM interactions, and thus their downstream cell death effects. This review will discuss current understanding of RHIM:RHIM interactions in normal cellular activation of necroptosis, from a structural and cell biology perspective. It will compare the mechanisms by which pathogens subvert these interactions in order to maintain their replicative and infective cycles and consider the similarities between RHIMs and other functional amyloid-forming proteins associated with cell death and innate immunity. It will discuss the implications of the heteromeric nature and structure of RHIM-based amyloid complexes in the context of other functional amyloids. Copyright © 2018. Published by Elsevier Ltd.

Regulatory role of periodontal ligament fibroblasts for innate immune cell function and differentiation.

PubMed

Konermann, Anna; Stabenow, Dirk; Knolle, Percy A; Held, Stefanie A E; Deschner, James; Jäger, Andreas

2012-10-01

Innate immunity is crucial for an effective host defense against pathogenic microorganisms in periodontal tissues. As periodontal ligament (PDL) cells synthesize immunomodulatory cytokines, the aim of this in vitro study was to investigate whether these cells can interact with innate immune cells. Resting and inflammatory primed (IL-1β, TNF-α, HMGB1) human PDL cells were co-cultured with human monocyte-derived dendritic cells or macrophages. Migration, phenotypic maturation and modulation of phagocytosis of Porphyromonas gingivalis by immune cells were investigated upon co-culture with PDL cells and/or their released soluble factors. PDL cells interacted with immune cells under both non-inflammatory and inflammatory conditions. Immune cell migration was significantly enhanced by co-culture with PDL cells, which also affected their phenotypic maturation both through cell-cell contact and through released soluble mediators. The dendritic cell maturation markers CD83 and CD86 were upregulated as much as both 'alternatively activated' M2 macrophage maturation markers CD23 and CD163. In contrast, the 'classically activated' M1 macrophage maturation marker CD64 was downregulated. Finally, PDL cells significantly enhanced the phagocytosis of Porphyromonas gingivalis by immune cells. Our experiments revealed that PDL cells are not only structural elements of the periodontium, but actively influence immune responses by interaction with innate immune cells.

Immune-Neuroendocrine Interactions and Autoimmune Diseases

PubMed Central

Jara, Luis J.; Navarro, Carmen; Medina, Gabriela; Vera-Lastra, Olga; Blanco, Francisco

2006-01-01

The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD. PMID:17162354

Crosstalk among Jasmonate, Salicylate and Ethylene Signaling Pathways in Plant Disease and Immune Responses.

PubMed

Yang, You-Xin; Ahammed, Golam J; Wu, Caijun; Fan, Shu-ying; Zhou, Yan-Hong

2015-01-01

Phytohormone crosstalk is crucial for plant defenses against pathogens and insects in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. These low molecular mass signals critically trigger and modulate plant resistance against biotrophic as well as necrotrophic pathogens through a complex signaling network that even involves participation of other hormones. Crosstalk among SA, JA and ET is mediated by different molecular players, considered as integral part of these crosscommunicating signal transduction pathways. Recent progress has revealed that the positive versus negative interactions among those pathways ultimately enable a plant to fine-tune its defense against specific aggressors. On the other hand, pathogens have evolved strategies to manipulate the signaling network to their favour in order to intensify virulence on host plant. Here we review recent advances and current knowledge on the role of classical primary defense hormones SA, JA and ET as well as their synergistic and antagonistic interaction in plant disease and immune responses. Crosstalk with other hormones such as abscisic acid, auxin, brassinosteroids, cytokinins and melatonin is also discussed mainly in plant disease resistance. In addition to our keen focus on hormonal crosstalk, this review also highlights potential implication of positive and negative regulatory interactions for developing an efficient disease management strategy through manipulation of hormone signaling in plant.

Bifidobacterial surface-exopolysaccharide facilitates commensal-host interaction through immune modulation and pathogen protection

PubMed Central

Fanning, Saranna; Hall, Lindsay J.; Cronin, Michelle; Zomer, Aldert; MacSharry, John; Goulding, David; O'Connell Motherway, Mary; Shanahan, Fergus; Nally, Kenneth; Dougan, Gordon; van Sinderen, Douwe

2012-01-01

Bifidobacteria comprise a significant proportion of the human gut microbiota. Several bifidobacterial strains are currently used as therapeutic interventions, claiming various health benefits by acting as probiotics. However, the precise mechanisms by which they maintain habitation within their host and consequently provide these benefits are not fully understood. Here we show that Bifidobacterium breve UCC2003 produces a cell surface-associated exopolysaccharide (EPS), the biosynthesis of which is directed by either half of a bidirectional gene cluster, thus leading to production of one of two possible EPSs. Alternate transcription of the two opposing halves of this cluster appears to be the result of promoter reorientation. Surface EPS provided stress tolerance and promoted in vivo persistence, but not initial colonization. Marked differences were observed in host immune response: strains producing surface EPS (EPS+) failed to elicit a strong immune response compared with EPS-deficient variants. Specifically, EPS production was shown to be linked to the evasion of adaptive B-cell responses. Furthermore, presence of EPS+ B. breve reduced colonization levels of the gut pathogen Citrobacter rodentium. Our data thus assigns a pivotal and beneficial role for EPS in modulating various aspects of bifidobacterial–host interaction, including the ability of commensal bacteria to remain immunologically silent and in turn provide pathogen protection. This finding enforces the probiotic concept and provides mechanistic insights into health-promoting benefits for both animal and human hosts. PMID:22308390

A Recombinant Horseshoe Crab Plasma Lectin Recognizes Specific Pathogen-Associated Molecular Patterns of Bacteria through Rhamnose

PubMed Central

Ng, Sim-Kun; Huang, Yu-Tsyr; Lee, Yuan-Chuan; Low, Ee-Ling; Chiu, Cheng-Hsun; Chen, Shiu-Ling; Mao, Liang-Chi; Chang, Margaret Dah-Tsyr

2014-01-01

Horseshoe crab is an ancient marine arthropod that, in the absence of a vertebrate-like immune system, relies solely on innate immune responses by defense molecules found in hemolymph plasma and granular hemocytes for host defense. A plasma lectin isolated from the hemolymph of Taiwanese Tachypleus tridentatus recognizes bacteria and lipopolysaccharides (LPSs), yet its structure and mechanism of action remain unclear, largely because of limited availability of horseshoe crabs and the lack of a heterogeneous expression system. In this study, we have successfully expressed and purified a soluble and functional recombinant horseshoe crab plasma lectin (rHPL) in an Escherichia coli system. Interestingly, rHPL bound not only to bacteria and LPSs like the native HPL but also to selective medically important pathogens isolated from clinical specimens, such as Gram-negative Pseudomonas aeruginosa and Klebsiella pneumoniae and Gram-positive Streptococcus pneumoniae serotypes. The binding was demonstrated to occur through a specific molecular interaction with rhamnose in pathogen-associated molecular patterns (PAMPs) on the bacterial surface. Additionally, rHPL inhibited the growth of P. aeruginosa PAO1 in a concentration-dependent manner. The results suggest that a specific protein-glycan interaction between rHPL and rhamnosyl residue may further facilitate development of novel diagnostic and therapeutic strategies for microbial pathogens. PMID:25541995

Transcriptome landscape of a bacterial pathogen under plant immunity.

PubMed

Nobori, Tatsuya; Velásquez, André C; Wu, Jingni; Kvitko, Brian H; Kremer, James M; Wang, Yiming; He, Sheng Yang; Tsuda, Kenichi

2018-03-27

Plant pathogens can cause serious diseases that impact global agriculture. The plant innate immunity, when fully activated, can halt pathogen growth in plants. Despite extensive studies into the molecular and genetic bases of plant immunity against pathogens, the influence of plant immunity in global pathogen metabolism to restrict pathogen growth is poorly understood. Here, we developed RNA sequencing pipelines for analyzing bacterial transcriptomes in planta and determined high-resolution transcriptome patterns of the foliar bacterial pathogen Pseudomonas syringae in Arabidopsis thaliana with a total of 27 combinations of plant immunity mutants and bacterial strains. Bacterial transcriptomes were analyzed at 6 h post infection to capture early effects of plant immunity on bacterial processes and to avoid secondary effects caused by different bacterial population densities in planta We identified specific "immune-responsive" bacterial genes and processes, including those that are activated in susceptible plants and suppressed by plant immune activation. Expression patterns of immune-responsive bacterial genes at the early time point were tightly linked to later bacterial growth levels in different host genotypes. Moreover, we found that a bacterial iron acquisition pathway is commonly suppressed by multiple plant immune-signaling pathways. Overexpression of a P. syringae sigma factor gene involved in iron regulation and other processes partially countered bacterial growth restriction during the plant immune response triggered by AvrRpt2. Collectively, this study defines the effects of plant immunity on the transcriptome of a bacterial pathogen and sheds light on the enigmatic mechanisms of bacterial growth inhibition during the plant immune response.

Sucrose and invertases, a part of the plant defense response to the biotic stresses

PubMed Central

Tauzin, Alexandra S.; Giardina, Thierry

2014-01-01

Sucrose is the main form of assimilated carbon which is produced during photosynthesis and then transported from source to sink tissues via the phloem. This disaccharide is known to have important roles as signaling molecule and it is involved in many metabolic processes in plants. Essential for plant growth and development, sucrose is engaged in plant defense by activating plant immune responses against pathogens. During infection, pathogens reallocate the plant sugars for their own needs forcing the plants to modify their sugar content and triggering their defense responses. Among enzymes that hydrolyze sucrose and alter carbohydrate partitioning, invertases have been reported to be affected during plant-pathogen interactions. Recent highlights on the role of invertases in the establishment of plant defense responses suggest a more complex regulation of sugar signaling in plant-pathogen interaction. PMID:25002866

Different subsets of natural killer T cells may vary in their roles in health and disease

PubMed Central

Kumar, Vipin; Delovitch, Terry L

2014-01-01

Natural killer T cells (NKT) can regulate innate and adaptive immune responses. Type I and type II NKT cell subsets recognize different lipid antigens presented by CD1d, an MHC class-I-like molecule. Most type I NKT cells express a semi-invariant T-cell receptor (TCR), but a major subset of type II NKT cells reactive to a self antigen sulphatide use an oligoclonal TCR. Whereas TCR-α dominates CD1d-lipid recognition by type I NKT cells, TCR-α and TCR-β contribute equally to CD1d-lipid recognition by type II NKT cells. These variable modes of NKT cell recognition of lipid–CD1d complexes activate a host of cytokine-dependent responses that can either exacerbate or protect from disease. Recent studies of chronic inflammatory and autoimmune diseases have led to a hypothesis that: (i) although type I NKT cells can promote pathogenic and regulatory responses, they are more frequently pathogenic, and (ii) type II NKT cells are predominantly inhibitory and protective from such responses and diseases. This review focuses on a further test of this hypothesis by the use of recently developed techniques, intravital imaging and mass cytometry, to analyse the molecular and cellular dynamics of type I and type II NKT cell antigen-presenting cell motility, interaction, activation and immunoregulation that promote immune responses leading to health versus disease outcomes. PMID:24428389

Host protein BSL1 associates with Phytophthora infestans RXLR effector AVR2 and the Solanum demissum Immune receptor R2 to mediate disease resistance.

PubMed

Saunders, Diane G O; Breen, Susan; Win, Joe; Schornack, Sebastian; Hein, Ingo; Bozkurt, Tolga O; Champouret, Nicolas; Vleeshouwers, Vivianne G A A; Birch, Paul R J; Gilroy, Eleanor M; Kamoun, Sophien

2012-08-01

Plant pathogens secrete effector proteins to modulate plant immunity and promote host colonization. Plant nucleotide binding leucine-rich repeat (NB-LRR) immunoreceptors recognize specific pathogen effectors directly or indirectly. Little is known about how NB-LRR proteins recognize effectors of filamentous plant pathogens, such as Phytophthora infestans. AVR2 belongs to a family of 13 sequence-divergent P. infestans RXLR effectors that are differentially recognized by members of the R2 NB-LRR family in Solanum demissum. We report that the putative plant phosphatase BSU-LIKE PROTEIN1 (BSL1) is required for R2-mediated perception of AVR2 and resistance to P. infestans. AVR2 associates with BSL1 and mediates the interaction of BSL1 with R2 in planta, possibly through the formation of a ternary complex. Strains of P. infestans that are virulent on R2 potatoes express an unrecognized form, Avr2-like (referred to as A2l). A2L can still interact with BSL1 but does not promote the association of BSL1 with R2. Our findings show that recognition of the P. infestans AVR2 effector by the NB-LRR protein R2 requires the putative phosphatase BSL1. This reveals that, similar to effectors of phytopathogenic bacteria, recognition of filamentous pathogen effectors can be mediated via a host protein that interacts with both the effector and the NB-LRR immunoreceptor.

Dynamic miRNA-mRNA regulations are essential for maintaining Drosophila immune homeostasis during Micrococcus luteus infection.

PubMed

Wei, Guanyun; Sun, Lianjie; Li, Ruimin; Li, Lei; Xu, Jiao; Ma, Fei

2018-04-01

Pathogen bacteria infections can lead to dynamic changes of microRNA (miRNA) and mRNA expression profiles, which may control synergistically the outcome of immune responses. To reveal the role of dynamic miRNA-mRNA regulation in Drosophila innate immune responses, we have detailedly analyzed the paired miRNA and mRNA expression profiles at three time points during Drosophila adult males with Micrococcus luteus (M. luteus) infection using RNA- and small RNA-seq data. Our results demonstrate that differentially expressed miRNAs and mRNAs represent extensively dynamic changes over three time points during Drosophila with M. luteus infection. The pathway enrichment analysis indicates that differentially expressed genes are involved in diverse signaling pathways, including Toll and Imd as well as orther signaling pathways at three time points during Drosophila with M. luteus infection. Remarkably, the dynamic change of miRNA expression is delayed by compared to mRNA expression change over three time points, implying that the "time" parameter should be considered when the function of miRNA/mRNA is further studied. In particular, the dynamic miRNA-mRNA regulatory networks have shown that miRNAs may synergistically regulate gene expressions of different signaling pathways to promote or inhibit innate immune responses and maintain homeostasis in Drosophila, and some new regulators involved in Drosophila innate immune response have been identified. Our findings strongly suggest that miRNA regulation is a key mechanism involved in fine-tuning cooperatively gene expressions of diverse signaling pathways to maintain innate immune response and homeostasis in Drosophila. Taken together, the present study reveals a novel role of dynamic miRNA-mRNA regulation in immune response to bacteria infection, and provides a new insight into the underlying molecular regulatory mechanism of Drosophila innate immune responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Getting to PTI of bacterial RNAs: Triggering plant innate immunity by extracellular RNAs from bacteria.

PubMed

Park, Yong-Soon; Lee, Boyoung; Ryu, Choong-Min

2016-07-02

Defense against diverse biotic and abiotic stresses requires the plant to distinguish between self and non-self signaling molecules. Pathogen/microbe-associated molecular patterns (PAMPs/MAMPs) are pivotal for triggering innate immunity in plants. Unlike in animals and humans, the precise roles of nucleic acids in plant innate immunity are unclear. We therefore investigated the effects of infiltration of total Pseudomonas syringae pv. tomato DC3000 (Pto DC3000) RNAs into Arabidopsis plants. The pathogen population was 10-fold lower in bacterial RNAs pre-treated Arabidopsis plants than in the control. Bacterial RNAs purity was confirmed by physical (sonication) and chemical (RNase A and proteinase K digestion) methods. The perception of bacterial RNAs, especially rRNAs, positively regulated mitogen-activated protein kinase (MAPK) and induced a reactive oxygen species burst, callose deposition, salicylic acid (SA) and jasmonic acid (JA) signaling, and defense-related genes. Therefore, bacterial RNAs function as a new MAMP that activates plant innate immunity, providing a new paradigm for plant-microbe interactions.

Peracetic Acid Treatment Generates Potent Inactivated Oral Vaccines from a Broad Range of Culturable Bacterial Species

PubMed Central

Moor, Kathrin; Wotzka, Sandra Y.; Toska, Albulena; Diard, Médéric; Hapfelmeier, Siegfried; Slack, Emma

2016-01-01

Our mucosal surfaces are the main sites of non-vector-borne pathogen entry, as well as the main interface with our commensal microbiota. We are still only beginning to understand how mucosal adaptive immunity interacts with commensal and pathogenic microbes to influence factors such as infectivity, phenotypic diversity, and within-host evolution. This is in part due to difficulties in generating specific mucosal adaptive immune responses without disrupting the mucosal microbial ecosystem itself. Here, we present a very simple tool to generate inactivated mucosal vaccines from a broad range of culturable bacteria. Oral gavage of 1010 peracetic acid-inactivated bacteria induces high-titer-specific intestinal IgA in the absence of any measurable inflammation or species invasion. As a proof of principle, we demonstrate that this technique is sufficient to provide fully protective immunity in the murine model of invasive non-typhoidal Salmonellosis, even in the face of severe innate immune deficiency. PMID:26904024

Does plant immunity play a critical role during initiation of the legume-rhizobium symbiosis?

PubMed

Tóth, Katalin; Stacey, Gary

2015-01-01

Plants are exposed to many different microbes in their habitats. These microbes may be benign or pathogenic, but in some cases they are beneficial for the host. The rhizosphere provides an especially rich palette for colonization by beneficial (associative and symbiotic) microorganisms, which raises the question as to how roots can distinguish such 'friends' from possible 'foes' (i.e., pathogens). Plants possess an innate immune system that can recognize pathogens, through an arsenal of protein receptors, including receptor-like kinases (RLKs) and receptor-like proteins (RLPs) located at the plasma membrane. In addition, the plant host has intracellular receptors (so called NBS-LRR proteins or R proteins) that directly or indirectly recognize molecules released by microbes into the plant cell. A successful cooperation between legume plants and rhizobia leads to beneficial symbiotic interaction. The key rhizobial, symbiotic signaling molecules [lipo-chitooligosaccharide Nod factors (NF)] are perceived by the host legume plant using lysin motif-domain containing RLKs. Perception of the symbiotic NFs trigger signaling cascades leading to bacterial infection and accommodation of the symbiont in a newly formed root organ, the nodule, resulting in a nitrogen-fixing root nodule symbiosis. The net result of this symbiosis is the intracellular colonization of the plant with thousands of bacteria; a process that seems to occur in spite of the immune ability of plants to prevent pathogen infection. In this review, we discuss the potential of the invading rhizobial symbiont to actively avoid this innate immune response, as well as specific examples of where the plant immune response may modulate rhizobial infection and host range.

Plant Proteomics and Peptidomics in Host-Pathogen Interactions: The Weapons Used by Each Side.

PubMed

Silva, Fabiana Aparecida Cavalcante; de Sousa Oliveira, Melquisedec; de Souza, Juliana Maria; Martins, Paulo Geovani Silva; Pestana-Calsa, Maria Clara; Junior, Tercilio Calsa

2017-01-01

Environmental biotic stress factors act continuously on plants, through multiple molecular interactions that eventually lead to the establishment and progress of symbiotic or pathogenic complex interactions. Proteins and peptides play noteworthy roles in such biological processes, usually being the main effectors since the initial recognizing and elicitor functions until the following transduction, gene regulation and physiological responses activities. Ranging from specific regulators to direct antimicrobial agents, plant or pathogen proteins and peptides comprise the arsenal available to each side in this biological war, resulting from the genetic coding potential inherited by each one. Post-translational research tools have widely contributed with valuable information on how the plant proteome works to achieve, maintain and adjust plant immunity in order to properly cope with the challenging pathogenic derived proteomes. These key proteins and peptides have great biotechnological potential since they represent distinctive features of each pathogen group (fungi, bacteria, viruses and other) in response to molecules of defense of host plants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Plant immunity against viruses: antiviral immune receptors in focus.

PubMed

Calil, Iara P; Fontes, Elizabeth P B

2017-03-01

Among the environmental limitations that affect plant growth, viruses cause major crop losses worldwide and represent serious threats to food security. Significant advances in the field of plant-virus interactions have led to an expansion of potential strategies for genetically engineered resistance in crops during recent years. Nevertheless, the evolution of viral virulence represents a constant challenge in agriculture that has led to a continuing interest in the molecular mechanisms of plant-virus interactions that affect disease or resistance. This review summarizes the molecular mechanisms of the antiviral immune system in plants and the latest breakthroughs reported in plant defence against viruses. Particular attention is given to the immune receptors and transduction pathways in antiviral innate immunity. Plants counteract viral infection with a sophisticated innate immune system that resembles the non-viral pathogenic system, which is broadly divided into pathogen-associated molecular pattern (PAMP)-triggered immunity and effector-triggered immunity. An additional recently uncovered virus-specific defence mechanism relies on host translation suppression mediated by a transmembrane immune receptor. In all cases, the recognition of the virus by the plant during infection is central for the activation of these innate defences, and, conversely, the detection of host plants enables the virus to activate virulence strategies. Plants also circumvent viral infection through RNA interference mechanisms by utilizing small RNAs, which are often suppressed by co-evolving virus suppressors. Additionally, plants defend themselves against viruses through hormone-mediated defences and activation of the ubiquitin-26S proteasome system (UPS), which alternatively impairs and facilitates viral infection. Therefore, plant defence and virulence strategies co-evolve and co-exist; hence, disease development is largely dependent on the extent and rate at which these opposing signals emerge in host and non-host interactions. A deeper understanding of plant antiviral immunity may facilitate innovative biotechnological, genetic and breeding approaches for crop protection and improvement. © The Author 2016. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane-association and innate antiviral immunity

PubMed Central

Liu, Helene Minyi; Loo, Yueh-Ming; Horner, Stacy M.; Zornetzer, Gregory A.; Katze, Michael G.; Gale, Michael

2012-01-01

Summary RIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, anti-viral signalling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or “translocon” containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signalling during acute RNA virus infection. 14-3-3ε is essential for the stable interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and initiation of innate immunity against hepatitis C virus and other pathogenic RNA viruses. Our results define 14-3-3ε as a key component of a RIG-I translocon required for innate antiviral immunity. PMID:22607805

The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity.

PubMed

Liu, Helene Minyi; Loo, Yueh-Ming; Horner, Stacy M; Zornetzer, Gregory A; Katze, Michael G; Gale, Michael

2012-05-17

RIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or "translocon" containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signaling during acute RNA virus infection. 14-3-3ε is essential for the stable interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and initiation of innate immunity against hepatitis C virus and other pathogenic RNA viruses. Our results define 14-3-3ε as a key component of a RIG-I translocon required for innate antiviral immunity. Copyright © 2012 Elsevier Inc. All rights reserved.

Bacterial effectors target the common signaling partner BAK1 to disrupt multiple MAMP receptor-signaling complexes and impede plant immunity.

PubMed

Shan, Libo; He, Ping; Li, Jianming; Heese, Antje; Peck, Scott C; Nürnberger, Thorsten; Martin, Gregory B; Sheen, Jen

2008-07-17

Successful pathogens have evolved strategies to interfere with host immune systems. For example, the ubiquitous plant pathogen Pseudomonas syringae injects two sequence-distinct effectors, AvrPto and AvrPtoB, to intercept convergent innate immune responses stimulated by multiple microbe-associated molecular patterns (MAMPs). However, the direct host targets and precise molecular mechanisms of bacterial effectors remain largely obscure. We show that AvrPto and AvrPtoB bind the Arabidopsis receptor-like kinase BAK1, a shared signaling partner of both the flagellin receptor FLS2 and the brassinosteroid receptor BRI1. This targeting interferes with ligand-dependent association of FLS2 with BAK1 during infection. It also impedes BAK1-dependent host immune responses to diverse other MAMPs and brassinosteroid signaling. Significantly, the structural basis of AvrPto-BAK1 interaction appears to be distinct from AvrPto-Pto association required for effector-triggered immunity. These findings uncover a unique strategy of bacterial pathogenesis where virulence effectors block signal transmission through a key common component of multiple MAMP-receptor complexes.

The function of the Mediator complex in plant immunity.

PubMed

An, Chuanfu; Mou, Zhonglin

2013-03-01

Upon pathogen infection, plants undergo dramatic transcriptome reprogramming to shift from normal growth and development to immune response. During this rapid process, the multiprotein Mediator complex has been recognized as an important player to fine-tune gene-specific and pathway-specific transcriptional reprogramming by acting as an adaptor/coregulator between sequence-specific transcription factor and RNA polymerase II (RNAPII). Here, we review current understanding of the role of five functionally characterized Mediator subunits (MED8, MED15, MED16, MED21 and MED25) in plant immunity. All these Mediator subunits positively regulate resistance against leaf-infecting biotrophic bacteria or necrotrophic fungi. While MED21 appears to regulate defense against fungal pathogens via relaying signals from upstream regulators and chromatin modification to RNAPII, the other four Mediator subunits locate at different positions of the defense network to convey phytohormone signal(s). Fully understanding the role of Mediator in plant immunity needs to characterize more Mediator subunits in both Arabidopsis and other plant species. Identification of interacting proteins of Mediator subunits will further help to reveal their specific regulatory mechanisms in plant immunity.

[Aspects of the innate immune response to intramammary Staphylococcus aureus infections in cattle].

PubMed

Pereyra, Elizabet A L; Dallard, Bibiana E; Calvinho, Luis F

2014-01-01

Staphylococcus aureus is the pathogen most frequently isolated from bovine mastitis worldwide, causing chronic intramammary infections that limit profitable dairying. The objective of this article is to characterize the mechanisms involved in S. aureus mammary gland infections considering two different aspects of the infectious process; on the one hand, the aspects involved in the host innate immune response and on the other hand, the capacity of this organism to evade the immune system and interact with different cell types. The exploration of S. aureus interactions with the immune response of bovine mammary gland will help identify targets to outline new preventive or curative alternatives for intramammary infections caused by this organism. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.

The AvrE superfamily: ancestral type III effectors involved in suppression of pathogen-associated molecular pattern-triggered immunity.

PubMed

Degrave, Alexandre; Siamer, Sabrina; Boureau, Tristan; Barny, Marie-Anne

2015-10-01

The AvrE superfamily of type III effectors (T3Es) is widespread among type III-dependent phytobacteria and plays a crucial role during bacterial pathogenesis. Members of the AvrE superfamily are vertically inherited core effectors, indicating an ancestral acquisition of these effectors in bacterial plant pathogens. AvrE-T3Es contribute significantly to virulence by suppressing pathogen-associated molecular pattern (PAMP)-triggered immunity. They inhibit salicylic acid-mediated plant defences, interfere with vesicular trafficking and promote bacterial growth in planta. AvrE-T3Es elicit cell death in both host and non-host plants independent of any known plant resistance protein, suggesting an original interaction with the plant immune system. Recent studies in yeast have indicated that they activate protein phosphatase 2A and inhibit serine palmitoyl transferase, the first enzyme of the sphingolipid biosynthesis pathway. In this review, we describe the current picture that has emerged from studies of the different members of this fascinating large family. © 2015 BSPP AND JOHN WILEY & SONS LTD.

Immunology of Gut Mucosal Vaccines

PubMed Central

Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

2011-01-01

Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

Extending the the behavioral immune system to political psychology: are political conservatism and disgust sensitivity really related?

PubMed

Tybur, Joshua M; Merriman, Leslie A; Hooper, Ann E Caldwell; McDonald, Melissa M; Navarrete, Carlos David

2010-10-26

Previous research suggests that several individual and cultural level attitudes, cognitions, and societal structures may have evolved to mitigate the pathogen threats posed by intergroup interactions. It has been suggested that these anti-pathogen defenses are at the root of conservative political ideology. Here, we test a hypothesis that political conservatism functions as a pathogen-avoidance strategy. Across three studies, we consistently find no relationship between sensitivity to pathogen disgust and multiple measures of political conservatism. These results are contrasted with theoretical perspectives suggesting a relationship between conservatism and pathogen avoidance, and with previous findings of a relationship between conservatism and disgust sensitivity.

Neuro-immune interactions in inflammation and host defense: Implications for transplantation.

PubMed

Chavan, Sangeeta S; Ma, Pingchuan; Chiu, Isaac M

2018-03-01

Sensory and autonomic neurons of the peripheral nervous system (PNS) play a critical role in regulating the immune system during tissue inflammation and host defense. Recent studies have identified the molecular mechanisms underlying the bidirectional communication between the nervous system and the immune system. Here, we highlight the studies that demonstrate the importance of the neuro-immune interactions in health and disease. Nociceptor sensory neurons detect immune mediators to produce pain, and release neuropeptides that act on the immune system to regulate inflammation. In parallel, neural reflex circuits including the vagus nerve-based inflammatory reflex are physiological regulators of inflammatory responses and cytokine production. In transplantation, neuro-immune communication could significantly impact the processes of host-pathogen defense, organ rejection, and wound healing. Emerging approaches to target the PNS such as bioelectronics could be useful in improving the outcome of transplantation. Therefore, understanding how the nervous system shapes the immune response could have important therapeutic ramifications for transplantation medicine. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

MORPHOLOGICAL CHANGES IN MICE LIVER IN DYNAMICS OF CONCANAVALIN A - INDUCED HEPATITIS.

PubMed

Pavlovych, S I; Makogon, N V; Grushka, N G; Bryzgina, T M; Janchiy, R I

The injure of the liver tissue and its infiltration by cells of the innate and adaptive immunity in dynamics of Con A-induced hepatitis in mice was studied. The semiquantitative method of damage rate of microcirculation channel and liver parenchyma was used, leukocyte liver infiltration and cellular composition of infiltrates were investigated also. Primary liver reaction to the Con-A was the inflammatory changes in the vascular bed, followed by disturbances in the parenchyma.The sufficient increasing of leukocyte migration to the liver was revealed. Besides, the neutrophile infiltration was increased first with a maximum at 6 hours of the experiment (63,9 ±4,6%, p<0,001 to the control level) ,and then the lymphocyte infiltration was increased with creation of manycellular lymphocytemacrophage infiltrates (62% at 48 hours comparing to 6 hours of experiment) and sufficient quantity of plasma cells population (4,9%, p<0,05 comparing to 6 hours of experiment). The obtained data gives the base to suggest that the elevated infiltration of liver tissue by leukocytes, particularly by lymphocytes and monocytes, together with necrotic death increasing creats the conditions for effective intracellular interaction and immune response to autoantigenes. This can be the essential pathogenic mechanism of development of autoimmune liver deseases.

Monitoring Extracellular Vesicle Cargo Active Uptake by Imaging Flow Cytometry.

PubMed

Ofir-Birin, Yifat; Abou Karam, Paula; Rudik, Ariel; Giladi, Tal; Porat, Ziv; Regev-Rudzki, Neta

2018-01-01

Extracellular vesicles are essential for long distance cell-cell communication. They function as carriers of different compounds, including proteins, lipids and nucleic acids. Pathogens, like malaria parasites ( Plasmodium falciparum, Pf ), excel in employing vesicle release to mediate cell communication in diverse processes, particularly in manipulating the host response. Establishing research tools to study the interface between pathogen-derived vesicles and their host recipient cells will greatly benefit the scientific community. Here, we present an imaging flow cytometry (IFC) method for monitoring the uptake of malaria-derived vesicles by host immune cells. By staining different cargo components, we were able to directly track the cargo's internalization over time and measure the kinetics of its delivery. Impressively, we demonstrate that this method can be used to specifically monitor the translocation of a specific protein within the cellular milieu upon internalization of parasitic cargo; namely, we were able to visually observe how uptaken parasitic Pf -DNA cargo leads to translocation of transcription factor IRF3 from the cytosol to the nucleus within the recipient immune cell. Our findings demonstrate that our method can be used to study cellular dynamics upon vesicle uptake in different host-pathogen and pathogen-pathogen systems.

Host–Multi-Pathogen Warfare: Pathogen Interactions in Co-infected Plants

PubMed Central

Abdullah, Araz S.; Moffat, Caroline S.; Lopez-Ruiz, Francisco J.; Gibberd, Mark R.; Hamblin, John; Zerihun, Ayalsew

2017-01-01

Studies of plant–pathogen interactions have historically focused on simple models of infection involving single host-single disease systems. However, plant infections often involve multiple species and/or genotypes and exhibit complexities not captured in single host-single disease systems. Here, we review recent insights into co-infection systems focusing on the dynamics of host-multi-pathogen interactions and the implications for host susceptibility/resistance. In co-infection systems, pathogen interactions include: (i) Competition, in which competing pathogens develop physical barriers or utilize toxins to exclude competitors from resource-dense niches; (ii) Cooperation, whereby pathogens beneficially interact, by providing mutual biochemical signals essential for pathogenesis, or through functional complementation via the exchange of resources necessary for survival; (iii) Coexistence, whereby pathogens can stably coexist through niche specialization. Furthermore, hosts are also able to, actively or passively, modulate niche competition through defense responses that target at least one pathogen. Typically, however, virulent pathogens subvert host defenses to facilitate infection, and responses elicited by one pathogen may be modified in the presence of another pathogen. Evidence also exists, albeit rare, of pathogens incorporating foreign genes that broaden niche adaptation and improve virulence. Throughout this review, we draw upon examples of co-infection systems from a range of pathogen types and identify outstanding questions for future innovation in disease control strategies. PMID:29118773

Neutrophils: Between Host Defence, Immune Modulation, and Tissue Injury

PubMed Central

Kruger, Philipp; Saffarzadeh, Mona; Weber, Alexander N. R.; Rieber, Nikolaus; Radsak, Markus; von Bernuth, Horst; Benarafa, Charaf; Roos, Dirk; Skokowa, Julia; Hartl, Dominik

2015-01-01

Neutrophils, the most abundant human immune cells, are rapidly recruited to sites of infection, where they fulfill their life-saving antimicrobial functions. While traditionally regarded as short-lived phagocytes, recent findings on long-term survival, neutrophil extracellular trap (NET) formation, heterogeneity and plasticity, suppressive functions, and tissue injury have expanded our understanding of their diverse role in infection and inflammation. This review summarises our current understanding of neutrophils in host-pathogen interactions and disease involvement, illustrating the versatility and plasticity of the neutrophil, moving between host defence, immune modulation, and tissue damage. PMID:25764063

Integrating Antimicrobial Therapy with Host Immunity to Fight Drug-Resistant Infections: Classical vs. Adaptive Treatment

PubMed Central

Gjini, Erida; Brito, Patricia H.

2016-01-01

Antimicrobial resistance of infectious agents is a growing problem worldwide. To prevent the continuing selection and spread of drug resistance, rational design of antibiotic treatment is needed, and the question of aggressive vs. moderate therapies is currently heatedly debated. Host immunity is an important, but often-overlooked factor in the clearance of drug-resistant infections. In this work, we compare aggressive and moderate antibiotic treatment, accounting for host immunity effects. We use mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic treatment. We compare classical (fixed dose and duration) and adaptive (coupled to pathogen load) treatment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of resistant bacteria. Our analysis and simulations uncover effective treatment strategies that promote synergy between the host immune system and the antimicrobial drug in clearing infection. Both in classical and adaptive treatment, we quantify how treatment timing and the strength of the immune response determine the success of moderate therapies. We explain key parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of resistance management. Emphasizing the sensitivity of treatment outcomes to the balance between external antibiotic intervention and endogenous natural defenses, our study calls for more empirical attention to host immunity processes. PMID:27078624

A Systems Biology Methodology Combining Transcriptome and Interactome Datasets to Assess the Implications of Cytokinin Signaling for Plant Immune Networks.

PubMed

Kunz, Meik; Dandekar, Thomas; Naseem, Muhammad

2017-01-01

Cytokinins (CKs) play an important role in plant growth and development. Also, several studies highlight the modulatory implications of CKs for plant-pathogen interaction. However, the underlying mechanisms of CK mediating immune networks in plants are still not fully understood. A detailed analysis of high-throughput transcriptome (RNA-Seq and microarrays) datasets under modulated conditions of plant CKs and its mergence with cellular interactome (large-scale protein-protein interaction data) has the potential to unlock the contribution of CKs to plant defense. Here, we specifically describe a detailed systems biology methodology pertinent to the acquisition and analysis of various omics datasets that delineate the role of plant CKs in impacting immune pathways in Arabidopsis.

Anti-Immune Strategies of Pathogenic Fungi

PubMed Central

Marcos, Caroline M.; de Oliveira, Haroldo C.; de Melo, Wanessa de Cássia M. Antunes; da Silva, Julhiany de Fátima; Assato, Patrícia A.; Scorzoni, Liliana; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Mendes-Giannini, Maria J. S.; Fusco-Almeida, Ana M.

2016-01-01

Pathogenic fungi have developed many strategies to evade the host immune system. Multiple escape mechanisms appear to function together to inhibit attack by the various stages of both the adaptive and the innate immune response. Thus, after entering the host, such pathogens fight to overcome the immune system to allow their survival, colonization and spread to different sites of infection. Consequently, the establishment of a successful infectious process is closely related to the ability of the pathogen to modulate attack by the immune system. Most strategies employed to subvert or exploit the immune system are shared among different species of fungi. In this review, we summarize the main strategies employed for immune evasion by some of the major pathogenic fungi. PMID:27896220

Regulatory Proteolysis in Arabidopsis-Pathogen Interactions.

PubMed

Pogány, Miklós; Dankó, Tamás; Kámán-Tóth, Evelin; Schwarczinger, Ildikó; Bozsó, Zoltán

2015-09-24

Approximately two and a half percent of protein coding genes in Arabidopsis encode enzymes with known or putative proteolytic activity. Proteases possess not only common housekeeping functions by recycling nonfunctional proteins. By irreversibly cleaving other proteins, they regulate crucial developmental processes and control responses to environmental changes. Regulatory proteolysis is also indispensable in interactions between plants and their microbial pathogens. Proteolytic cleavage is simultaneously used both by plant cells, to recognize and inactivate invading pathogens, and by microbes, to overcome the immune system of the plant and successfully colonize host cells. In this review, we present available results on the group of proteases in the model plant Arabidopsis thaliana whose functions in microbial pathogenesis were confirmed. Pathogen-derived proteolytic factors are also discussed when they are involved in the cleavage of host metabolites. Considering the wealth of review papers available in the field of the ubiquitin-26S proteasome system results on the ubiquitin cascade are not presented. Arabidopsis and its pathogens are conferred with abundant sets of proteases. This review compiles a list of those that are apparently involved in an interaction between the plant and its pathogens, also presenting their molecular partners when available.

Pathogenic Leptospira Species Acquire Factor H and Vitronectin via the Surface Protein LcpA

PubMed Central

da Silva, Ludmila Bezerra; Miragaia, Lidia dos Santos; Breda, Leandro Carvalho Dantas; Abe, Cecilia Mari; Schmidt, Mariana Costa Braga; Moro, Ana Maria; Monaris, Denize; Conde, Jonas Nascimento; Józsi, Mihály; Isaac, Lourdes; Abreu, Patrícia Antônia Estima

2014-01-01

Upon infection, pathogenic Leptospira species bind several complement regulators in order to overcome host innate immunity. We previously characterized a 20-kDa leptospiral surface protein which interacts with C4b binding protein (C4BP): leptospiral complement regulator-acquiring protein A (LcpA). Here we show that LcpA also interacts with human factor H (FH), which remains functionally active once bound to the protein. Antibodies directed against short consensus repeat 20 (SCR20) inhibited binding of FH to LcpA by approximately 90%, thus confirming that this particular domain is involved in the interaction. We have also shown for the first time that leptospires bind human vitronectin and that the interaction is mediated by LcpA. Coincubation with heparin blocked LcpA-vitronectin interaction in a dose-dependent manner, strongly suggesting that binding may occur through the heparin binding domains of vitronectin. LcpA also bound to the terminal pathway component C9 and inhibited Zn2+-induced polymerization and membrane attack complex (MAC) formation. Competitive binding assays indicated that LcpA interacts with C4BP, FH, and vitronectin through distinct sites. Taken together, our findings indicate that LcpA may play a role in leptospiral immune evasion. PMID:25534939

Pathogenic Leptospira species acquire factor H and vitronectin via the surface protein LcpA.

PubMed

da Silva, Ludmila Bezerra; Miragaia, Lidia Dos Santos; Breda, Leandro Carvalho Dantas; Abe, Cecilia Mari; Schmidt, Mariana Costa Braga; Moro, Ana Maria; Monaris, Denize; Conde, Jonas Nascimento; Józsi, Mihály; Isaac, Lourdes; Abreu, Patrícia Antônia Estima; Barbosa, Angela Silva

2015-03-01

Upon infection, pathogenic Leptospira species bind several complement regulators in order to overcome host innate immunity. We previously characterized a 20-kDa leptospiral surface protein which interacts with C4b binding protein (C4BP): leptospiral complement regulator-acquiring protein A (LcpA). Here we show that LcpA also interacts with human factor H (FH), which remains functionally active once bound to the protein. Antibodies directed against short consensus repeat 20 (SCR20) inhibited binding of FH to LcpA by approximately 90%, thus confirming that this particular domain is involved in the interaction. We have also shown for the first time that leptospires bind human vitronectin and that the interaction is mediated by LcpA. Coincubation with heparin blocked LcpA-vitronectin interaction in a dose-dependent manner, strongly suggesting that binding may occur through the heparin binding domains of vitronectin. LcpA also bound to the terminal pathway component C9 and inhibited Zn(2+)-induced polymerization and membrane attack complex (MAC) formation. Competitive binding assays indicated that LcpA interacts with C4BP, FH, and vitronectin through distinct sites. Taken together, our findings indicate that LcpA may play a role in leptospiral immune evasion. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Environmental controls, oceanography and population dynamics of pathogens and harmful algal blooms: connecting sources to human exposure.

PubMed

Dyble, Julianne; Bienfang, Paul; Dusek, Eva; Hitchcock, Gary; Holland, Fred; Laws, Ed; Lerczak, James; McGillicuddy, Dennis J; Minnett, Peter; Moore, Stephanie K; O'Kelly, Charles; Solo-Gabriele, Helena; Wang, John D

2008-11-07

Coupled physical-biological models are capable of linking the complex interactions between environmental factors and physical hydrodynamics to simulate the growth, toxicity and transport of infectious pathogens and harmful algal blooms (HABs). Such simulations can be used to assess and predict the impact of pathogens and HABs on human health. Given the widespread and increasing reliance of coastal communities on aquatic systems for drinking water, seafood and recreation, such predictions are critical for making informed resource management decisions. Here we identify three challenges to making this connection between pathogens/HABs and human health: predicting concentrations and toxicity; identifying the spatial and temporal scales of population and ecosystem interactions; and applying the understanding of population dynamics of pathogens/HABs to management strategies. We elaborate on the need to meet each of these challenges, describe how modeling approaches can be used and discuss strategies for moving forward in addressing these challenges.

Advances in imaging the innate and adaptive immune response to Toxoplasma gondii

PubMed Central

John, Beena; Weninger, Wolfgang; Hunter, Christopher A

2011-01-01

Toxoplasma gondii is an intracellular protozoan parasite that infects a wide variety of warm-blooded hosts and can have devastating effects in the developing fetus as well as the immunocompromised host. An appreciation of how this organism interacts with the host immune system is crucial to understanding the pathogenesis of this disease. The last decade has been marked by the application of various imaging techniques, such as bioluminescent imaging as well as confocal and multiphoton microscopy to study toxoplasmosis. The ability to manipulate parasites to express fluorescent/bioluminescent markers or model antigens/enzymes combined with the development of reporter mice that allow the detection of distinct immune populations have been crucial to the success of many of these studies. These approaches have permitted the visualization of parasites and immune cells in real-time and provided new insights into the nature of host–pathogen interactions. This article highlights some of the advances in imaging techniques, their strengths and weaknesses, and how these techniques have impacted our understanding of the interaction between parasites and various immune populations during toxoplasmosis. PMID:20860479

Overwintering Is Associated with Reduced Expression of Immune Genes and Higher Susceptibility to Virus Infection in Honey Bees

PubMed Central

Steinmann, Nadja; Corona, Miguel; Neumann, Peter; Dainat, Benjamin

2015-01-01

The eusocial honey bee, Apis mellifera, has evolved remarkable abilities to survive extreme seasonal differences in temperature and availability of resources by dividing the worker caste into two groups that differ in physiology and lifespan: summer and winter bees. Most of the recent major losses of managed honey bee colonies occur during the winter, suggesting that winter bees may have compromised immune function and higher susceptibility to diseases. We tested this hypothesis by comparing the expression of eight immune genes and naturally occurring infection levels of deformed wing virus (DWV), one of the most widespread viruses in A. mellifera populations, between summer and winter bees. Possible interactions between immune response and physiological activity were tested by measuring the expression of vitellogenin and methyl farnesoate epoxidase, a gene coding for the last enzyme involved in juvenile hormone biosynthesis. Our data show that high DWV loads in winter bees correlate with reduced expression of genes involved in the cellular immune response and physiological activity and high expression of humoral immune genes involved in antibacterial defense compared with summer bees. This expression pattern could reflect evolutionary adaptations to resist bacterial pathogens and economize energy during the winter under a pathogen landscape with reduced risk of pathogenic viral infections. The outbreak of Varroa destructor infestation could have overcome these adaptations by promoting the transmission of viruses. Our results suggest that reduced cellular immune function during the winter may have increased honey bee’s susceptibility to DWV. These results contribute to our understanding of honey bee colony losses in temperate regions. PMID:26121358

The role of inflammation in depression: from evolutionary imperative to modern treatment target.

PubMed

Miller, Andrew H; Raison, Charles L

2016-01-01

Crosstalk between inflammatory pathways and neurocircuits in the brain can lead to behavioural responses, such as avoidance and alarm, that are likely to have provided early humans with an evolutionary advantage in their interactions with pathogens and predators. However, in modern times, such interactions between inflammation and the brain appear to drive the development of depression and may contribute to non-responsiveness to current antidepressant therapies. Recent data have elucidated the mechanisms by which the innate and adaptive immune systems interact with neurotransmitters and neurocircuits to influence the risk for depression. Here, we detail our current understanding of these pathways and discuss the therapeutic potential of targeting the immune system to treat depression.

Transcriptional response of Musca domestica larvae to bacterial infection.

PubMed

Tang, Ting; Li, Xiang; Yang, Xue; Yu, Xue; Wang, Jianhui; Liu, Fengsong; Huang, Dawei

2014-01-01

The house fly Musca domestica, a cosmopolitan dipteran insect, is a significant vector for human and animal bacterial pathogens, but little is known about its immune response to these pathogens. To address this issue, we inoculated the larvae with a mixture of Escherichia coli and Staphylococcus aureus and profiled the transcriptome 6, 24, and 48 h thereafter. Many genes known to controlling innate immunity in insects were induced following infection, including genes encoding pattern recognition proteins (PGRPs), various components of the Toll and IMD signaling pathways and of the proPO-activating and redox systems, and multiple antimicrobial peptides. Interestingly, we also uncovered a large set of novel immune response genes including two broad-spectrum antimicrobial peptides (muscin and domesticin), which might have evolved to adapt to house-fly's unique ecological environments. Finally, genes mediating oxidative phosphorylation were repressed at 48 h post-infection, suggesting disruption of energy homeostasis and mitochondrial function at the late stages of infection. Collectively, our data reveal dynamic changes in gene expression following bacterial infection in the house fly, paving the way for future in-depth analysis of M. domestica's immune system.

Scaling laws describe memories of host-pathogen riposte in the HIV population.

PubMed

Barton, John P; Kardar, Mehran; Chakraborty, Arup K

2015-02-17

The enormous genetic diversity and mutability of HIV has prevented effective control of this virus by natural immune responses or vaccination. Evolution of the circulating HIV population has thus occurred in response to diverse, ultimately ineffective, immune selection pressures that randomly change from host to host. We show that the interplay between the diversity of human immune responses and the ways that HIV mutates to evade them results in distinct sets of sequences defined by similar collectively coupled mutations. Scaling laws that relate these sets of sequences resemble those observed in linguistics and other branches of inquiry, and dynamics reminiscent of neural networks are observed. Like neural networks that store memories of past stimulation, the circulating HIV population stores memories of host-pathogen combat won by the virus. We describe an exactly solvable model that captures the main qualitative features of the sets of sequences and a simple mechanistic model for the origin of the observed scaling laws. Our results define collective mutational pathways used by HIV to evade human immune responses, which could guide vaccine design.

Modelling the impact of vaccination on curtailing Haemophilus influenzae serotype 'a'.

PubMed

Konini, Angjelina; Moghadas, Seyed M

2015-12-21

Haemophilus influenzae serotype a (Hia) is a human-restricted bacterial pathogen transmitted via direct contacts with an infectious individual. Currently, there is no vaccine available for prevention of Hia, and the disease is treated with antibiotics upon diagnosis. With ongoing efforts for the development of an anti-Hia protein-polysaccharide conjugated vaccine, we sought to investigate the effect of vaccination on curtailing Hia infection. We present the first stochastic model of Hia transmission and control dynamics, and parameterize it using available estimates in the literature. Since both naturally acquired and vaccine-induced immunity wane with time, model simulations show three important results. First, vaccination of only newborns cannot eliminate the pathogen from the population, even when a booster program is implemented with a high coverage. Second, achieving and maintaining a sufficiently high level of herd immunity for pathogen elimination requires vaccination of susceptible individuals in addition to a high vaccination coverage of newborns. Third, for a low vaccination rate of susceptible individuals, a high coverage of booster dose may be needed to raise the level of herd immunity for Hia eradication. Our findings highlight the importance of vaccination and timely boosting of the individual׳s immunity within the expected duration of vaccine-induced protection against Hia. When an anti-Hia vaccine becomes available, enhanced surveillance of Hia incidence and herd immunity could help determine vaccination rates and timelines for booster doses necessary to eliminate Hia from affected populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Membrane rafts: a potential gateway for bacterial entry into host cells.

PubMed

Hartlova, Anetta; Cerveny, Lukas; Hubalek, Martin; Krocova, Zuzana; Stulik, Jiri

2010-04-01

Pathogenic bacteria have developed various mechanisms to evade host immune defense systems. Invasion of pathogenic bacteria requires interaction of the pathogen with host receptors, followed by activation of signal transduction pathways and rearrangement of the cytoskeleton to facilitate bacterial entry. Numerous bacteria exploit specialized plasma membrane microdomains, commonly called membrane rafts, which are rich in cholesterol, sphingolipids and a special set of signaling molecules which allow entry to host cells and establishment of a protected niche within the host. This review focuses on the current understanding of the raft hypothesis and the means by which pathogenic bacteria subvert membrane microdomains to promote infection.

Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function

PubMed Central

Hajishengallis, George; Wang, Min; Liang, Shuang; Triantafilou, Martha; Triantafilou, Kathy

2008-01-01

We report a mechanism of microbial evasion of Toll-like receptor (TLR)-mediated immunity that depends on CXCR4 exploitation. Specifically, the oral/systemic pathogen Porphyromonas gingivalis induces cross-talk between CXCR4 and TLR2 in human monocytes or mouse macrophages and undermines host defense. This is accomplished through its surface fimbriae, which induce CXCR4/TLR2 co-association in lipid rafts and interact with both receptors: Binding to CXCR4 induces cAMP-dependent protein kinase A (PKA) signaling, which in turn inhibits TLR2-mediated proinflammatory and antimicrobial responses to the pathogen. This outcome enables P. gingivalis to resist clearance in vitro and in vivo and thus to promote its adaptive fitness. However, a specific CXCR4 antagonist abrogates this immune evasion mechanism and offers a promising counterstrategy for the control of P. gingivalis periodontal or systemic infections. PMID:18765807

Recent Advances in Aptamers Targeting Immune System.

PubMed

Hu, Piao-Ping

2017-02-01

The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

Ambient ozone and pulmonary innate immunity

PubMed Central

Al-Hegelan, Mashael; Tighe, Robert M.; Castillo, Christian; Hollingsworth, John W.

2013-01-01

Ambient ozone is a criteria air pollutant that impacts both human morbidity and mortality. The effect of ozone inhalation includes both toxicity to lung tissue and alteration of the host immunologic response. The innate immune system facilitates immediate recognition of both foreign pathogens and tissue damage. Emerging evidence supports that ozone can modify the host innate immune response and that this response to inhaled ozone is dependent on genes of innate immunity. Improved understanding of the complex interaction between environmental ozone and host innate immunity will provide fundamental insight into the pathogenesis of inflammatory airways disease. We review the current evidence supporting that environmental ozone inhalation: (1) modifies cell types required for intact innate immunity, (2) is partially dependent on genes of innate immunity, (3) primes pulmonary innate immune responses to LPS, and (4) contributes to innate-adaptive immune system cross-talk. PMID:21132467

The transcriptome of Spodoptera exigua larvae exposed to different types of microbes.

PubMed

Pascual, Laura; Jakubowska, Agata K; Blanca, Jose M; Cañizares, Joaquin; Ferré, Juan; Gloeckner, Gernot; Vogel, Heiko; Herrero, Salvador

2012-08-01

We have obtained and characterized the transcriptome of Spodoptera exigua larvae with special emphasis on pathogen-induced genes. In order to obtain a highly representative transcriptome, we have pooled RNA from diverse insect colonies, conditions and tissues. Sequenced cDNA included samples from 3 geographically different colonies. Enrichment of RNA from pathogen-related genes was accomplished by exposing larvae to different pathogenic and non-pathogenic microbial agents such as the bacteria Bacillus thuringiensis, Micrococcus luteus, and Escherichia coli, the yeast Saccharomyces cerevisiae, and the S. exigua nucleopolyhedrovirus (SeMNPV). In addition, to avoid the loss of tissue-specific genes we included cDNA from the midgut, fat body, hemocytes and integument derived from pathogen exposed insects. RNA obtained from the different types of samples was pooled, normalized and sequenced. Analysis of the sequences obtained using the Roche 454 FLX and Sanger methods has allowed the generation of the largest public set of ESTs from S. exigua, including a large group of immune genes, and the identification of an important number of SSR (simple sequence repeats) and SNVs (single nucleotide variants: SNPs and INDELs) with potential use as genetic markers. Moreover, data mining has allowed the discovery of novel RNA viruses with potential influence in the insect population dynamics and the larval interactions with the microbial pesticides that are currently in use for the biological control of this pest. Copyright © 2012 Elsevier Ltd. All rights reserved.

Synergistic Parasite-Pathogen Interactions Mediated by Host Immunity Can Drive the Collapse of Honeybee Colonies

PubMed Central

Nazzi, Francesco; Brown, Sam P.; Annoscia, Desiderato; Del Piccolo, Fabio; Di Prisco, Gennaro; Varricchio, Paola; Della Vedova, Giorgio; Cattonaro, Federica; Caprio, Emilio; Pennacchio, Francesco

2012-01-01

The health of the honeybee and, indirectly, global crop production are threatened by several biotic and abiotic factors, which play a poorly defined role in the induction of widespread colony losses. Recent descriptive studies suggest that colony losses are often related to the interaction between pathogens and other stress factors, including parasites. Through an integrated analysis of the population and molecular changes associated with the collapse of honeybee colonies infested by the parasitic mite Varroa destructor, we show that this parasite can de-stabilise the within-host dynamics of Deformed wing virus (DWV), transforming a cryptic and vertically transmitted virus into a rapidly replicating killer, which attains lethal levels late in the season. The de-stabilisation of DWV infection is associated with an immunosuppression syndrome, characterized by a strong down-regulation of the transcription factor NF-κB. The centrality of NF-κB in host responses to a range of environmental challenges suggests that this transcription factor can act as a common currency underlying colony collapse that may be triggered by different causes. Our results offer an integrated account for the multifactorial origin of honeybee losses and a new framework for assessing, and possibly mitigating, the impact of environmental challenges on honeybee health. PMID:22719246

Active Suppression of Early Immune Response in Tobacco by the Human Pathogen Salmonella Typhimurium

PubMed Central

Shirron, Natali; Yaron, Sima

2011-01-01

The persistence of enteric pathogens on plants has been studied extensively, mainly due to the potential hazard of human pathogens such as Salmonella enterica being able to invade and survive in/on plants. Factors involved in the interactions between enteric bacteria and plants have been identified and consequently it was hypothesized that plants may be vectors or alternative hosts for enteric pathogens. To survive, endophytic bacteria have to escape the plant immune systems, which function at different levels through the plant-bacteria interactions. To understand how S. enterica survives endophyticaly we conducted a detailed analysis on its ability to elicit or evade the plant immune response. The models of this study were Nicotiana tabacum plants and cells suspension exposed to S. enterica serovar Typhimurium. The plant immune response was analyzed by looking at tissue damage and by testing oxidative burst and pH changes. It was found that S. Typhimurium did not promote disease symptoms in the contaminated plants. Live S. Typhimurium did not trigger the production of an oxidative burst and pH changes by the plant cells, while heat killed or chloramphenicol treated S. Typhimurium and purified LPS of Salmonella were significant elicitors, indicating that S. Typhimurium actively suppress the plant response. By looking at the plant response to mutants defective in virulence factors we showed that the suppression depends on secreted factors. Deletion of invA reduced the ability of S. Typhimurium to suppress oxidative burst and pH changes, indicating that a functional SPI1 TTSS is required for the suppression. This study demonstrates that plant colonization by S. Typhimurium is indeed an active process. S. Typhimurium utilizes adaptive strategies of altering innate plant perception systems to improve its fitness in the plant habitat. All together these results suggest a complex mechanism for perception of S. Typhimurium by plants. PMID:21541320

The genomic and epidemiological dynamics of human influenza A virus.

PubMed

Rambaut, Andrew; Pybus, Oliver G; Nelson, Martha I; Viboud, Cecile; Taubenberger, Jeffery K; Holmes, Edward C

2008-05-29

The evolutionary interaction between influenza A virus and the human immune system, manifest as 'antigenic drift' of the viral haemagglutinin, is one of the best described patterns in molecular evolution. However, little is known about the genome-scale evolutionary dynamics of this pathogen. Similarly, how genomic processes relate to global influenza epidemiology, in which the A/H3N2 and A/H1N1 subtypes co-circulate, is poorly understood. Here through an analysis of 1,302 complete viral genomes sampled from temperate populations in both hemispheres, we show that the genomic evolution of influenza A virus is characterized by a complex interplay between frequent reassortment and periodic selective sweeps. The A/H3N2 and A/H1N1 subtypes exhibit different evolutionary dynamics, with diverse lineages circulating in A/H1N1, indicative of weaker antigenic drift. These results suggest a sink-source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions.

A note on the effects of replenishment of depleted cells on HIV infection dynamics: A graph-theoretic approach

NASA Astrophysics Data System (ADS)

Mukwembi, Simon

2008-02-01

We study the effects of the rate of replacement of dead cells by either healthy cells or by infected cells on HIV infection dynamics through a graph-theoretic approach. Our framework takes into account a reasonable amount of the immune action to any pathogen and the local cell interactions that occur in the lymph nodes. Our results, in an extremal case where dead cells are highly likely to be replaced by healthy cells, show that all cells become healthy in a finite number of steps of given order and infection stops propagating. Further, for this extremal case, we give an algebraic formula for the number of infected cells at any given time in the HIV progression. We also find a sufficient condition, determined by dead cell replacement rate, which guarantees that an infected patient is continually positive, and give bounds on the number of infected, healthy and dead cells at any given time. We apply our theoretical results to a recently proposed model of the HIV infection dynamics.

Temperature and population density: interactional effects of environmental factors on phenotypic plasticity, immune defenses, and disease resistance in an insect pest.

PubMed

Silva, Farley W S; Elliot, Simon L

2016-06-01

Temperature and crowding are key environmental factors mediating the transmission and epizooty of infectious disease in ectotherm animals. The host physiology may be altered in a temperature-dependent manner and thus affects the pathogen development and course of diseases within an individual and host population, or the transmission rates (or infectivity) of pathogens shift linearly with the host population density. To our understanding, the knowledge of interactive and synergistic effects of temperature and population density on the host-pathogen system is limited. Here, we tested the interactional effects of these environmental factors on phenotypic plasticity, immune defenses, and disease resistance in the velvetbean caterpillar Anticarsia gemmatalis . Upon egg hatching, caterpillars were reared in thermostat-controlled chambers in a 2 × 4 factorial design: density (1 or 8 caterpillars/pot) and temperature (20, 24, 28, or 32°C). Of the immune defenses assessed, encapsulation response was directly affected by none of the environmental factors; capsule melanization increased with temperature in both lone- and group-reared caterpillars, although the lone-reared ones presented the most evident response, and hemocyte numbers decreased with temperature regardless of the population density. Temperature, but not population density, affected considerably the time from inoculation to death of velvetbean caterpillar. Thus, velvetbean caterpillars succumbed to Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) more quickly at higher temperatures than at lower temperatures. As hypothesized, temperature likely affected caterpillars' movement rates, and thus the contact between conspecifics, which in turn affected the phenotypic expression of group-reared caterpillars. Our results suggest that environmental factors, mainly temperature, strongly affect both the course of disease in velvetbean caterpillar population and its defenses against pathogens. As a soybean pest, velvetbean caterpillar may increase its damage on soybean fields under a scenario of global warming as caterpillars may reach the developmental resistance faster, and thus decrease their susceptibility to biological control by AgMNPV.

Statistical Physics of T-Cell Development and Pathogen Specificity

NASA Astrophysics Data System (ADS)

Košmrlj, Andrej; Kardar, Mehran; Chakraborty, Arup K.

2013-04-01

In addition to an innate immune system that battles pathogens in a nonspecific fashion, higher organisms, such as humans, possess an adaptive immune system to combat diverse (and evolving) microbial pathogens. Remarkably, the adaptive immune system mounts pathogen-specific responses, which can be recalled upon reinfection with the same pathogen. It is difficult to see how the adaptive immune system can be preprogrammed to respond specifically to a vast and unknown set of pathogens. Although major advances have been made in understanding pertinent molecular and cellular phenomena, the precise principles that govern many aspects of an immune response are largely unknown. We discuss complementary approaches from statistical mechanics and cell biology that can shed light on how key components of the adaptive immune system, T cells, develop to enable pathogen-specific responses against many diverse pathogens. The mechanistic understanding that emerges has implications for how host genetics may influence the development of T cells with differing responses to the human immunodeficiency virus (HIV) infection.

Local interactions lead to pathogen-driven change to host population dynamics.

PubMed

Boots, Michael; Childs, Dylan; Reuman, Daniel C; Mealor, Michael

2009-10-13

Individuals tend to interact more strongly with nearby individuals or within particular social groups. Recent theoretical advances have demonstrated that these within-population relationships can have fundamental implications for ecological and evolutionary dynamics. In particular, contact networks are crucial to the spread and evolution of disease. However, the theory remains largely untested experimentally. Here, we manipulate habitat viscosity and thereby the frequency of local interactions in an insect-pathogen model system in which the virus had previously been shown to have little effect on host population dynamics. At high viscosity, the pathogen caused the collapse of dominant and otherwise stable host generation cycles. Modeling shows that this collapse can be explained by an increase in the frequency of intracohort interactions relative to intercohort interactions, leading to more disease transmission. Our work emphasizes that spatial structure can subtly mediate intraspecific competition and the effects of natural enemies. A decrease in dispersal in a population may actually (sometimes rather counterintuitively) intensify the effects of parasites. Broadly, because anthropological and environmental change often cause changes in population mixing, our work highlights the potential for dramatic changes in the effects of parasites on host populations.

A downy mildew effector attenuates salicylic acid-triggered immunity in Arabidopsis by interacting with the host mediator complex.

PubMed

Caillaud, Marie-Cécile; Asai, Shuta; Rallapalli, Ghanasyam; Piquerez, Sophie; Fabro, Georgina; Jones, Jonathan D G

2013-12-01

Plants are continually exposed to pathogen attack but usually remain healthy because they can activate defences upon perception of microbes. However, pathogens have evolved to overcome plant immunity by delivering effectors into the plant cell to attenuate defence, resulting in disease. Recent studies suggest that some effectors may manipulate host transcription, but the specific mechanisms by which such effectors promote susceptibility remain unclear. We study the oomycete downy mildew pathogen of Arabidopsis, Hyaloperonospora arabidopsidis (Hpa), and show here that the nuclear-localized effector HaRxL44 interacts with Mediator subunit 19a (MED19a), resulting in the degradation of MED19a in a proteasome-dependent manner. The Mediator complex of ∼25 proteins is broadly conserved in eukaryotes and mediates the interaction between transcriptional regulators and RNA polymerase II. We found MED19a to be a positive regulator of immunity against Hpa. Expression profiling experiments reveal transcriptional changes resembling jasmonic acid/ethylene (JA/ET) signalling in the presence of HaRxL44, and also 3 d after infection with Hpa. Elevated JA/ET signalling is associated with a decrease in salicylic acid (SA)-triggered immunity (SATI) in Arabidopsis plants expressing HaRxL44 and in med19a loss-of-function mutants, whereas SATI is elevated in plants overexpressing MED19a. Using a PR1::GUS reporter, we discovered that Hpa suppresses PR1 expression specifically in cells containing haustoria, into which RxLR effectors are delivered, but not in nonhaustoriated adjacent cells, which show high PR1::GUS expression levels. Thus, HaRxL44 interferes with Mediator function by degrading MED19, shifting the balance of defence transcription from SA-responsive defence to JA/ET-signalling, and enhancing susceptibility to biotrophs by attenuating SA-dependent gene expression.

A Downy Mildew Effector Attenuates Salicylic Acid–Triggered Immunity in Arabidopsis by Interacting with the Host Mediator Complex

PubMed Central

Caillaud, Marie-Cécile; Asai, Shuta; Rallapalli, Ghanasyam; Piquerez, Sophie; Fabro, Georgina; Jones, Jonathan D. G.

2013-01-01

Plants are continually exposed to pathogen attack but usually remain healthy because they can activate defences upon perception of microbes. However, pathogens have evolved to overcome plant immunity by delivering effectors into the plant cell to attenuate defence, resulting in disease. Recent studies suggest that some effectors may manipulate host transcription, but the specific mechanisms by which such effectors promote susceptibility remain unclear. We study the oomycete downy mildew pathogen of Arabidopsis, Hyaloperonospora arabidopsidis (Hpa), and show here that the nuclear-localized effector HaRxL44 interacts with Mediator subunit 19a (MED19a), resulting in the degradation of MED19a in a proteasome-dependent manner. The Mediator complex of ∼25 proteins is broadly conserved in eukaryotes and mediates the interaction between transcriptional regulators and RNA polymerase II. We found MED19a to be a positive regulator of immunity against Hpa. Expression profiling experiments reveal transcriptional changes resembling jasmonic acid/ethylene (JA/ET) signalling in the presence of HaRxL44, and also 3 d after infection with Hpa. Elevated JA/ET signalling is associated with a decrease in salicylic acid (SA)–triggered immunity (SATI) in Arabidopsis plants expressing HaRxL44 and in med19a loss-of-function mutants, whereas SATI is elevated in plants overexpressing MED19a. Using a PR1::GUS reporter, we discovered that Hpa suppresses PR1 expression specifically in cells containing haustoria, into which RxLR effectors are delivered, but not in nonhaustoriated adjacent cells, which show high PR1::GUS expression levels. Thus, HaRxL44 interferes with Mediator function by degrading MED19, shifting the balance of defence transcription from SA-responsive defence to JA/ET-signalling, and enhancing susceptibility to biotrophs by attenuating SA-dependent gene expression. PMID:24339748

The race between infection and immunity - how do pathogens set the pace?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ribiero, Ruy M

2009-01-01

Infection is often referred to as a race between pathogen and immune response. This metaphor suggests that slower growing pathogens should be more easily controlled. However, a growing body ofevidence shows that many chronic infections are caused by failure to control slow growing pathogens. The slow growth of pathogens appears to directly affect the kinetics of the immune response. Compared with the response to fast growing pathogens, the T cell response to slow pathogens is delayed in its initiation, lymphocyte expansion is slow and the response often fails to clear the pathogen, leading to chronic infection. Understanding the 'rules ofthemore » race' for slow growing pathogens has important implications for vaccine design and immune control of many chronic infections.« less

Differential Coexpression Analysis Reveals Extensive Rewiring of Arabidopsis Gene Coexpression in Response to Pseudomonas syringae Infection

PubMed Central

Jiang, Zhenhong; Dong, Xiaobao; Li, Zhi-Gang; He, Fei; Zhang, Ziding

2016-01-01

Plant defense responses to pathogens involve massive transcriptional reprogramming. Recently, differential coexpression analysis has been developed to study the rewiring of gene networks through microarray data, which is becoming an important complement to traditional differential expression analysis. Using time-series microarray data of Arabidopsis thaliana infected with Pseudomonas syringae, we analyzed Arabidopsis defense responses to P. syringae through differential coexpression analysis. Overall, we found that differential coexpression was a common phenomenon of plant immunity. Genes that were frequently involved in differential coexpression tend to be related to plant immune responses. Importantly, many of those genes have similar average expression levels between normal plant growth and pathogen infection but have different coexpression partners. By integrating the Arabidopsis regulatory network into our analysis, we identified several transcription factors that may be regulators of differential coexpression during plant immune responses. We also observed extensive differential coexpression between genes within the same metabolic pathways. Several metabolic pathways, such as photosynthesis light reactions, exhibited significant changes in expression correlation between normal growth and pathogen infection. Taken together, differential coexpression analysis provides a new strategy for analyzing transcriptional data related to plant defense responses and new insights into the understanding of plant-pathogen interactions. PMID:27721457

Card9 mediates susceptibility to intestinal pathogens through microbiota modulation and control of bacterial virulence.

PubMed

Lamas, Bruno; Michel, Marie-Laure; Waldschmitt, Nadine; Pham, Hang-Phuong; Zacharioudaki, Vassiliki; Dupraz, Louise; Delacre, Myriam; Natividad, Jane M; Costa, Gregory Da; Planchais, Julien; Sovran, Bruno; Bridonneau, Chantal; Six, Adrien; Langella, Philippe; Richard, Mathias L; Chamaillard, Mathias; Sokol, Harry

2017-08-08

In association with innate and adaptive immunity, the microbiota controls the colonisation resistance against intestinal pathogens. Caspase recruitment domain 9 ( CARD9 ), a key innate immunity gene, is required to shape a normal gut microbiota. Card9 -/- mice are more susceptible to the enteric mouse pathogen Citrobacter rodentium that mimics human infections with enteropathogenic and enterohaemorrhagic Escherichia coli . Here, we examined how CARD9 controls C. rodentium infection susceptibility through microbiota-dependent and microbiota-independent mechanisms. C. rodentium infection was assessed in conventional and germ-free (GF) wild-type (WT) and Card9 -/- mice. To explore the impact of Card9 -/- microbiota in infection susceptibility, GF WT mice were colonised with WT (WT→GF) or Card9 -/- ( Card9 -/- →GF) microbiota before C. rodentium infection. Microbiota composition was determined by 16S rDNA gene sequencing. Inflammation severity was determined by histology score and lipocalin level. Microbiota-host immune system interactions were assessed by quantitative PCR analysis. CARD9 controls pathogen virulence in a microbiota-independent manner by supporting a specific humoral response. Higher susceptibility to C. rodentium -induced colitis was observed in Card9 -/- →GF mice. The microbiota of Card9 -/- mice failed to outcompete the monosaccharide-consuming C. rodentium , worsening the infection severity. A polysaccharide-enriched diet counteracted the ecological advantage of C. rodentium and the defective pathogen-specific antibody response in Card9 -/- mice. CARD9 modulates the susceptibility to intestinal infection by controlling the pathogen virulence in a microbiota-dependent and microbiota-independent manner. Genetic susceptibility to intestinal pathogens can be overridden by diet intervention that restores humoural immunity and a competing microbiota. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Structural Basis for Dual-Inhibition Mechanism of a Non-Classical Kazal-Type Serine Protease Inhibitor from Horseshoe Crab in Complex with Subtilisin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shenoy, Rajesh T.; Thangamani, Saravanan; Velazquez-Campoy, Adrian

2011-04-26

Serine proteases play a crucial role in host-pathogen interactions. In the innate immune system of invertebrates, multi-domain protease inhibitors are important for the regulation of host-pathogen interactions and antimicrobial activities. Serine protease inhibitors, 9.3-kDa CrSPI isoforms 1 and 2, have been identified from the hepatopancreas of the horseshoe crab, Carcinoscorpius rotundicauda. The CrSPIs were biochemically active, especially CrSPI-1, which potently inhibited subtilisin (Ki=1.43 nM). CrSPI has been grouped with the non-classical Kazal-type inhibitors due to its unusual cysteine distribution. Here we report the crystal structure of CrSPI-1 in complex with subtilisin at 2.6 Å resolution and the results of biophysicalmore » interaction studies. The CrSPI-1 molecule has two domains arranged in an extended conformation. These two domains act as heads that independently interact with two separate subtilisin molecules, resulting in the inhibition of subtilisin activity at a ratio of 1:2 (inhibitor to protease). Each subtilisin molecule interacts with the reactive site loop from each domain of CrSPI-1 through a standard canonical binding mode and forms a single ternary complex. In addition, we propose the substrate preferences of each domain of CrSPI-1. Domain 2 is specific towards the bacterial protease subtilisin, while domain 1 is likely to interact with the host protease, Furin. Elucidation of the structure of the CrSPI-1: subtilisin (1:2) ternary complex increases our understanding of host-pathogen interactions in the innate immune system at the molecular level and provides new strategies for immunomodulation.« less

Protein interaction networks at the host-microbe interface in Diaphorina citri, the insect vector of the citrus greening pathogen.

PubMed

Ramsey, J S; Chavez, J D; Johnson, R; Hosseinzadeh, S; Mahoney, J E; Mohr, J P; Robison, F; Zhong, X; Hall, D G; MacCoss, M; Bruce, J; Cilia, M

2017-02-01

The Asian citrus psyllid ( Diaphorina citri) is the insect vector responsible for the worldwide spread of ' Candidatus Liberibacter asiaticus' (CLas), the bacterial pathogen associated with citrus greening disease. Developmental changes in the insect vector impact pathogen transmission, such that D. citri transmission of CLas is more efficient when bacteria are acquired by nymphs when compared with adults. We hypothesize that expression changes in the D. citri immune system and commensal microbiota occur during development and regulate vector competency. In support of this hypothesis, more proteins, with greater fold changes, were differentially expressed in response to CLas in adults when compared with nymphs, including insect proteins involved in bacterial adhesion and immunity. Compared with nymphs, adult insects had a higher titre of CLas and the bacterial endosymbionts Wolbachia, Profftella and Carsonella. All Wolbachia and Profftella proteins differentially expressed between nymphs and adults are upregulated in adults, while most differentially expressed Carsonella proteins are upregulated in nymphs. Discovery of protein interaction networks has broad applicability to the study of host-microbe relationships. Using protein interaction reporter technology, a D. citri haemocyanin protein highly upregulated in response to CLas was found to physically interact with the CLas coenzyme A (CoA) biosynthesis enzyme phosphopantothenoylcysteine synthetase/decarboxylase. CLas pantothenate kinase, which catalyses the rate-limiting step of CoA biosynthesis, was found to interact with a D. citri myosin protein. Two Carsonella enzymes involved in histidine and tryptophan biosynthesis were found to physically interact with D. citri proteins. These co-evolved protein interaction networks at the host-microbe interface are highly specific targets for controlling the insect vector responsible for the spread of citrus greening.

Protein interaction networks at the host–microbe interface in Diaphorina citri, the insect vector of the citrus greening pathogen

PubMed Central

Chavez, J. D.; Johnson, R.; Hosseinzadeh, S.; Mahoney, J. E.; Mohr, J. P.; Robison, F.; Zhong, X.; Hall, D. G.; MacCoss, M.; Bruce, J.; Cilia, M.

2017-01-01

The Asian citrus psyllid (Diaphorina citri) is the insect vector responsible for the worldwide spread of ‘Candidatus Liberibacter asiaticus’ (CLas), the bacterial pathogen associated with citrus greening disease. Developmental changes in the insect vector impact pathogen transmission, such that D. citri transmission of CLas is more efficient when bacteria are acquired by nymphs when compared with adults. We hypothesize that expression changes in the D. citri immune system and commensal microbiota occur during development and regulate vector competency. In support of this hypothesis, more proteins, with greater fold changes, were differentially expressed in response to CLas in adults when compared with nymphs, including insect proteins involved in bacterial adhesion and immunity. Compared with nymphs, adult insects had a higher titre of CLas and the bacterial endosymbionts Wolbachia, Profftella and Carsonella. All Wolbachia and Profftella proteins differentially expressed between nymphs and adults are upregulated in adults, while most differentially expressed Carsonella proteins are upregulated in nymphs. Discovery of protein interaction networks has broad applicability to the study of host–microbe relationships. Using protein interaction reporter technology, a D. citri haemocyanin protein highly upregulated in response to CLas was found to physically interact with the CLas coenzyme A (CoA) biosynthesis enzyme phosphopantothenoylcysteine synthetase/decarboxylase. CLas pantothenate kinase, which catalyses the rate-limiting step of CoA biosynthesis, was found to interact with a D. citri myosin protein. Two Carsonella enzymes involved in histidine and tryptophan biosynthesis were found to physically interact with D. citri proteins. These co-evolved protein interaction networks at the host–microbe interface are highly specific targets for controlling the insect vector responsible for the spread of citrus greening. PMID:28386418

Deciphering the landscape of host barriers to Listeria monocytogenes infection

PubMed Central

Zhang, Ting; Abel, Sören; Abel zur Wiesch, Pia; Sasabe, Jumpei; Davis, Brigid M.; Higgins, Darren E.; Waldor, Matthew K.

2017-01-01

Listeria monocytogenes is a common food-borne pathogen that can disseminate from the intestine and infect multiple organs. Here, we used sequence tag-based analysis of microbial populations (STAMP) to investigate L. monocytogenes population dynamics during infection. We created a genetically barcoded library of murinized L. monocytogenes and then used deep sequencing to track the pathogen’s dissemination routes and quantify its founding population (Nb) sizes in different organs. We found that the pathogen disseminates from the gastrointestinal tract to distal sites through multiple independent routes and that Nb sizes vary greatly among tissues, indicative of diverse host barriers to infection. Unexpectedly, comparative analyses of sequence tags revealed that fecally excreted organisms are largely derived from the very small number of L. monocytogenes cells that colonize the gallbladder. Immune depletion studies suggest that distinct innate immune cells restrict the pathogen’s capacity to establish replicative niches in the spleen and liver. Finally, studies in germ-free mice suggest that the microbiota plays a critical role in the development of the splenic, but not the hepatic, barriers that prevent L. monocytogenes from seeding these organs. Collectively, these observations illustrate the potency of the STAMP approach to decipher the impact of host factors on population dynamics of pathogens during infection. PMID:28559314

Dual RNA regulatory control of a Staphylococcus aureus virulence factor.

PubMed

Chabelskaya, Svetlana; Bordeau, Valérie; Felden, Brice

2014-04-01

In pathogens, the accurate programming of virulence gene expression is essential for infection. It is achieved by sophisticated arrays of regulatory proteins and ribonucleic acids (sRNAs), but in many cases their contributions and connections are not yet known. Based on genetic, biochemical and structural evidence, we report that the expression pattern of a Staphylococcus aureus host immune evasion protein is enabled by the collaborative actions of RNAIII and small pathogenicity island RNA D (SprD). Their combined expression profiles during bacterial growth permit early and transient synthesis of Sbi to avoid host immune responses. Together, these two sRNAs use antisense mechanisms to monitor Sbi expression at the translational level. Deletion analysis combined with structural analysis of RNAIII in complex with its novel messenger RNA (mRNA) target indicate that three distant RNAIII domains interact with distinct sites of the sbi mRNA and that two locations are deep in the sbi coding region. Through distinct domains, RNAIII lowers production of two proteins required for avoiding innate host immunity, staphylococcal protein A and Sbi. Toeprints and in vivo mutational analysis reveal a novel regulatory module within RNAIII essential for attenuation of Sbi translation. The sophisticated translational control of mRNA by two differentially expressed sRNAs ensures supervision of host immune escape by a major pathogen.

Autoacetylation of the Ralstonia solanacearum effector PopP2 targets a lysine residue essential for RRS1-R-mediated immunity in Arabidopsis.

PubMed

Tasset, Céline; Bernoux, Maud; Jauneau, Alain; Pouzet, Cécile; Brière, Christian; Kieffer-Jacquinod, Sylvie; Rivas, Susana; Marco, Yves; Deslandes, Laurent

2010-11-18

Type III effector proteins from bacterial pathogens manipulate components of host immunity to suppress defence responses and promote pathogen development. In plants, host proteins targeted by some effectors called avirulence proteins are surveyed by plant disease resistance proteins referred to as "guards". The Ralstonia solanacearum effector protein PopP2 triggers immunity in Arabidopsis following its perception by the RRS1-R resistance protein. Here, we show that PopP2 interacts with RRS1-R in the nucleus of living plant cells. PopP2 belongs to the YopJ-like family of cysteine proteases, which share a conserved catalytic triad that includes a highly conserved cysteine residue. The catalytic cysteine mutant PopP2-C321A is impaired in its avirulence activity although it is still able to interact with RRS1-R. In addition, PopP2 prevents proteasomal degradation of RRS1-R, independent of the presence of an integral PopP2 catalytic core. A liquid chromatography/tandem mass spectrometry analysis showed that PopP2 displays acetyl-transferase activity leading to its autoacetylation on a particular lysine residue, which is well conserved among all members of the YopJ family. These data suggest that this lysine residue may correspond to a key binding site for acetyl-coenzyme A required for protein activity. Indeed, mutation of this lysine in PopP2 abolishes RRS1-R-mediated immunity. In agreement with the guard hypothesis, our results favour the idea that activation of the plant immune response by RRS1-R depends not only on the physical interaction between the two proteins but also on its perception of PopP2 enzymatic activity.

Investigating the effect of key mutations on the conformational dynamics of toll-like receptor dimers through molecular dynamics simulations and protein structure networks.

PubMed

Mahita, Jarjapu; Sowdhamini, Ramanathan

2018-04-01

The Toll-like receptors (TLRs) are critical components of the innate immune system due to their ability to detect conserved pathogen-associated molecular patterns, present in bacteria, viruses, and other microorganisms. Ligand detection by TLRs leads to a signaling cascade, mediated by interactions among TIR domains present in the receptors, the bridging adaptors and sorting adaptors. The BB loop is a highly conserved region present in the TIR domain and is crucial for mediating interactions among TIR domain-containing proteins. Mutations in the BB loop of the Toll-like receptors, such as the A795P mutation in TLR3 and the P712H mutation (Lps d mutation) in TLR4, have been reported to disrupt or alter downstream signaling. While the phenotypic effect of these mutations is known, the underlying effect of these mutations on the structure, dynamics and interactions with other TIR domain-containing proteins is not well understood. Here, we have attempted to investigate the effect of the BB loop mutations on the dimer form of TLRs, using TLR2 and TLR3 as case studies. Our results based on molecular dynamics simulations, protein-protein interaction analyses and protein structure network analyses highlight significant differences between the dimer interfaces of the wild-type and mutant forms and provide a logical reasoning for the effect of these mutations on adaptor binding to TLRs. Furthermore, it also leads us to propose a hypothesis for the differential requirement of signaling and bridging adaptors by TLRs. This could aid in further understanding of the mechanisms governing such signaling pathways. © 2018 Wiley Periodicals, Inc.

Special issue Oceans and Humans Health: the ecology of marine opportunists.

PubMed

Burge, Colleen A; Kim, Catherine J S; Lyles, Jillian M; Harvell, C Drew

2013-05-01

Opportunistic marine pathogens, like opportunistic terrestrial pathogens, are ubiquitous in the environment (waters, sediments, and organisms) and only cause disease in immune-compromised or stressed hosts. In this review, we discuss four host-pathogen interactions within the marine environment that are typically considered opportunistic: sea fan coral-fungus, eelgrass-Labyrinthula zosterae, sea fan-Labyrinthulomycetes, and hard clam-Quahog Parasite Unknown with particular focus on disease ecology, parasite pathology, host response, and known associated environmental conditions. Disease is a natural part of all ecosystems; however, in some cases, a shift in the balance between the host, pathogen, and the environment may lead to epizootics in natural or cultured populations. In marine systems, host-microbe interactions are less understood than their terrestrial counterparts. The biological and physical changes to the world's oceans, coupled with other anthropogenic influences, will likely lead to more opportunistic diseases in the marine environment.

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions.

PubMed

Hebecker, Betty; Vlaic, Sebastian; Conrad, Theresia; Bauer, Michael; Brunke, Sascha; Kapitan, Mario; Linde, Jörg; Hube, Bernhard; Jacobsen, Ilse D

2016-11-03

Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses.

Dual-species transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions

PubMed Central

Hebecker, Betty; Vlaic, Sebastian; Conrad, Theresia; Bauer, Michael; Brunke, Sascha; Kapitan, Mario; Linde, Jörg; Hube, Bernhard; Jacobsen, Ilse D.

2016-01-01

Candida albicans is a common cause of life-threatening fungal bloodstream infections. In the murine model of systemic candidiasis, the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To better understand these organ-specific differences in host-pathogen interaction, we performed gene expression profiling of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We observed a delayed transcriptional immune response accompanied by late induction of fungal stress response genes in the kidneys. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptome resembling response to phagocytosis, suggesting that phagocytes contribute significantly to fungal control in the liver. Notably, C. albicans hypha-associated genes were upregulated in the absence of visible filamentation in the liver, indicating an uncoupling of gene expression and morphology and a morphology-independent effect by hypha-associated genes in this organ. Consistently, integration of host and pathogen transcriptional data in an inter-species gene regulatory network indicated connections of C. albicans cell wall remodelling and metabolism to the organ-specific immune responses. PMID:27808111

An Evolution-Based Screen for Genetic Differentiation between Anopheles Sister Taxa Enriches for Detection of Functional Immune Factors

PubMed Central

Takashima, Eizo; Williams, Marni; Eiglmeier, Karin; Pain, Adrien; Guelbeogo, Wamdaogo M.; Gneme, Awa; Brito-Fravallo, Emma; Holm, Inge; Lavazec, Catherine; Sagnon, N’Fale; Baxter, Richard H.; Riehle, Michelle M.; Vernick, Kenneth D.

2015-01-01

Nucleotide variation patterns across species are shaped by the processes of natural selection, including exposure to environmental pathogens. We examined patterns of genetic variation in two sister species, Anopheles gambiae and Anopheles coluzzii, both efficient natural vectors of human malaria in West Africa. We used the differentiation signature displayed by a known coordinate selective sweep of immune genes APL1 and TEP1 in A. coluzzii to design a population genetic screen trained on the sweep, classified a panel of 26 potential immune genes for concordance with the signature, and functionally tested their immune phenotypes. The screen results were strongly predictive for genes with protective immune phenotypes: genes meeting the screen criteria were significantly more likely to display a functional phenotype against malaria infection than genes not meeting the criteria (p = 0.0005). Thus, an evolution-based screen can efficiently prioritize candidate genes for labor-intensive downstream functional testing, and safely allow the elimination of genes not meeting the screen criteria. The suite of immune genes with characteristics similar to the APL1-TEP1 selective sweep appears to be more widespread in the A. coluzzii genome than previously recognized. The immune gene differentiation may be a consequence of adaptation of A. coluzzii to new pathogens encountered in its niche expansion during the separation from A. gambiae, although the role, if any of natural selection by Plasmodium is unknown. Application of the screen allowed identification of new functional immune factors, and assignment of new functions to known factors. We describe biochemical binding interactions between immune proteins that underlie functional activity for malaria infection, which highlights the interplay between pathogen specificity and the structure of immune complexes. We also find that most malaria-protective immune factors display phenotypes for either human or rodent malaria, with broad specificity a rarity. PMID:26633695

The plant host pathogen interface: cell wall and membrane dynamics of pathogen-induced responses.

PubMed

Day, Brad; Graham, Terry

2007-10-01

Perception of pathogens by their hosts is the outcome of a highly coordinated and sophisticated surveillance network, tightly regulated by both host and pathogen elicitors, effectors, and signaling processes. In this article, we focus on two relatively well-studied host-pathogens systems, one involving a bacterial-plant interaction (Pseudomonas syringae-Arabidopsis) and the other involving an oomycete-plant interaction (Phytophthora sojae-soybean). We discuss the status of current research related to events occurring at the host-pathogen interface in these two systems, and how these events influence the organization and activation of resistance responses in the respective hosts. This recent research has revealed that in addition to the previously identified resistance machinery (R-proteins, molecular chaperones, etc.), the dynamics of the cell wall, membrane trafficking, and the actin cytoskeleton are intimately associated with the activation of resistance in plants. Specifically, in Arabidopsis, a possible connection between the actin machinery and R-protein- mediated induction of disease resistance is described. In the case of the P. sojae-soybean interaction, we describe the fact that a classical basal resistance elicitor, the cell wall glucan elicitor from the pathogen, can directly activate host hypersensitive cell death, which is apparently modulated in a race-specific manner by the presence of R genes in the host.

Understanding the immune system architecture and transcriptome responses to southern rice black-streaked dwarf virus in Sogatella furcifera.

PubMed

Wang, Lin; Tang, Nan; Gao, Xinlei; Guo, Dongyang; Chang, Zhaoxia; Fu, Yating; Akinyemi, Ibukun A; Wu, Qingfa

2016-11-02

Sogatella furcifera, the white-backed planthopper (WBPH), has become one of the most destructive pests in rice production owing to its plant sap-sucking behavior and efficient transmission of Southern rice black-streaked dwarf virus (SRBSDV) in a circulative, propagative and persistent manner. The dynamic and complex SRBSDV-WBPH-rice plant interaction is still poorly understood. In this study, based on a homology-based genome-wide analysis, 348 immune-related genes belonging to 28 families were identified in WBPH. A transcriptome analysis of non-viruliferous (NVF) and viruliferous groups with high viral titers (HVT) and median viral titers (MVT) revealed that feeding on SRBSDV-infected rice plants has a significant impact on gene expression, regardless of viral titers in insects. We identified 278 up-regulated and 406 down-regulated genes shared among the NVF, MVT, and HVT groups and detected significant down-regulation of primary metabolism-related genes and oxidoreductase. In viruliferous WBPH with viral titer-specific transcriptome changes, 1,906 and 1,467 genes exhibited strict monotonically increasing and decreasing expression, respectively. The RNAi pathway was the major antiviral response to increasing viral titers among diverse immune responses. These results clarify the responses of immune genes and the transcriptome of WBPH to SRBSDV and improve our knowledge of the functional relationship between pathogen, vector, and host.

Macrophage and T cell dynamics during the development and disintegration of mycobacterial granulomas.

PubMed

Egen, Jackson G; Rothfuchs, Antonio Gigliotti; Feng, Carl G; Winter, Nathalie; Sher, Alan; Germain, Ronald N

2008-02-01

Granulomas play a key role in host protection against mycobacterial pathogens, with their breakdown contributing to exacerbated disease. To better understand the initiation and maintenance of these structures, we employed both high-resolution multiplex static imaging and intravital multiphoton microscopy of Mycobacterium bovis BCG-induced liver granulomas. We found that Kupffer cells directly capture blood-borne bacteria and subsequently nucleate formation of a nascent granuloma by recruiting both uninfected liver-resident macrophages and blood-derived monocytes. Within the mature granuloma, these myeloid cell populations formed a relatively immobile cellular matrix that interacted with a highly dynamic effector T cell population. The efficient recruitment of these T cells was highly dependent on TNF-alpha-derived signals, which also maintained the granuloma structure through preferential effects on uninfected macrophage populations. By characterizing the migration of both innate and adaptive immune cells throughout the process of granuloma development, these studies provide a new perspective on the cellular events involved in mycobacterial containment and escape.

The Skin Microbiome: Is It Affected by UV-induced Immune Suppression?

PubMed Central

Patra, VijayKumar; Byrne, Scott N.; Wolf, Peter

2016-01-01

Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin’s microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs) that interfere with UV-induced immune suppression. PMID:27559331