Impact of Childhood Malnutrition on Host Defense and Infection.

PubMed

Ibrahim, Marwa K; Zambruni, Mara; Melby, Christopher L; Melby, Peter C

2017-10-01

The global impact of childhood malnutrition is staggering. The synergism between malnutrition and infection contributes substantially to childhood morbidity and mortality. Anthropometric indicators of malnutrition are associated with the increased risk and severity of infections caused by many pathogens, including viruses, bacteria, protozoa, and helminths. Since childhood malnutrition commonly involves the inadequate intake of protein and calories, with superimposed micronutrient deficiencies, the causal factors involved in impaired host defense are usually not defined. This review focuses on literature related to impaired host defense and the risk of infection in primary childhood malnutrition. Particular attention is given to longitudinal and prospective cohort human studies and studies of experimental animal models that address causal, mechanistic relationships between malnutrition and host defense. Protein and micronutrient deficiencies impact the hematopoietic and lymphoid organs and compromise both innate and adaptive immune functions. Malnutrition-related changes in intestinal microbiota contribute to growth faltering and dysregulated inflammation and immune function. Although substantial progress has been made in understanding the malnutrition-infection synergism, critical gaps in our understanding remain. We highlight the need for mechanistic studies that can lead to targeted interventions to improve host defense and reduce the morbidity and mortality of infectious diseases in this vulnerable population. Copyright © 2017 American Society for Microbiology.

Central importance of immunoglobulin A in host defense against Giardia spp.

PubMed

Langford, T Dianne; Housley, Michael P; Boes, Marianne; Chen, Jianzhu; Kagnoff, Martin F; Gillin, Frances D; Eckmann, Lars

2002-01-01

The protozoan pathogen Giardia is an important cause of parasitic diarrheal disease worldwide. It colonizes the lumen of the small intestine, suggesting that effective host defenses must act luminally. Immunoglobulin A (IgA) antibodies are presumed to be important for controlling Giardia infection, but direct evidence for this function is lacking. B-cell-independent effector mechanisms also exist and may be equally important for antigiardial host defense. To determine the importance of the immunoglobulin isotypes that are transported into the intestinal lumen, IgA and IgM, for antigiardial host defense, we infected gene-targeted mice lacking IgA-expressing B-cells, IgM-secreting B-cells, or all B-cells as controls with Giardia muris or Giardia lamblia GS/M-83-H7. We found that IgA-deficient mice could not eradicate either G. muris or G. lamblia infection, demonstrating that IgA is required for their clearance. Furthermore, although neither B-cell-deficient nor IgA-deficient mice could clear G. muris infections, IgA-deficient mice controlled infection significantly better than B-cell-deficient mice, suggesting the existence of B-cell-dependent but IgA-independent antigiardial defenses. In contrast, mice deficient for secreted IgM antibodies cleared G. muris infection normally, indicating that they have no unique functions in antigiardial host defense. These data, together with the finding that B-cell-deficient mice have some, albeit limited, residual capacity to control G. muris infection, show that IgA-dependent host defenses are central for eradicating Giardia spp. Moreover, B-cell-dependent but IgA-independent and B-cell-independent antigiardial host defenses exist but are less important for controlling infection.

Fibrinogen Is at the Interface of Host Defense and Pathogen Virulence in Staphylococcus aureus Infection

PubMed Central

Ko, Ya-Ping; Flick, Matthew J.

2017-01-01

Fibrinogen not only plays a pivotal role in hemostasis but also serves key roles in antimicrobial host defense. As a rapidly assembled provisional matrix protein, fibrin(ogen) can function as an early line of host protection by limiting bacterial growth, suppressing dissemination of microbes to distant sites, and mediating host bacterial killing. Fibrinogen-mediated host antimicrobial activity occurs predominantly through two general mechanisms, namely, fibrin matrices functioning as a protective barrier and fibrin(ogen) directly or indirectly driving host protective immune function. The potential of fibrin to limit bacterial infection and disease has been countered by numerous bacterial species evolving and maintaining virulence factors that engage hemostatic system components within vertebrate hosts. Bacterial factors have been isolated that simply bind fibrinogen or fibrin, promote fibrin polymer formation, or promote fibrin dissolution. Staphylococcus aureus is an opportunistic gram-positive bacterium, the causative agent of a wide range of human infectious diseases, and a prime example of a pathogen exquisitely sensitive to host fibrinogen. Indeed, current data suggest fibrinogen serves as a context-dependent determinant of host defense or pathogen virulence in Staphylococcus infection whose ultimate contribution is dictated by the expression of S. aureus virulence factors, the path of infection, and the tissue microenvironment. PMID:27056151

Increased host aggression as an induced defense against slave-making ants

PubMed Central

Pennings, Pleuni S.; Foitzik, Susanne

2011-01-01

Slave-making ants reduce the fitness of surrounding host colonies through regular raids, causing the loss of brood and frequently queen and worker death. Consequently, hosts developed defenses against slave raids such as specific recognition and aggression toward social parasites, and indeed, we show that host ants react more aggressively toward slavemakers than toward nonparasitic competitors. Permanent behavioral defenses can be costly, and if social parasite impact varies in time and space, inducible defenses, which are only expressed after slavemaker detection, can be adaptive. We demonstrate for the first time an induced defense against slave-making ants: Cues from the slavemaker Protomognathus americanus caused an unspecific but long-lasting behavioral response in Temnothorax host ants. A 5-min within-nest encounter with a dead slavemaker raised the aggression level in T. longispinosus host colonies. Contrarily, encounters with nonparasitic competitors did not elicit aggressive responses toward non-nestmates. Increased aggression can be adaptive if a slavemaker encounter reliably indicates a forthcoming attack and if aggression increases postraid survival. Host aggression was elevated over 3 days, showing the ability of host ants to remember parasite encounters. The response disappeared after 2 weeks, possibly because by then the benefits of increased aggression counterbalance potential costs associated with it. PMID:22476194

Chemerin regulation and role in host defense.

PubMed

Zabel, Brian A; Kwitniewski, Mateusz; Banas, Magdalena; Zabieglo, Katarzyna; Murzyn, Krzysztof; Cichy, Joanna

2014-01-01

Chemerin is a widely distributed multifunctional secreted protein implicated in immune cell migration, adipogenesis, osteoblastogenesis, angiogenesis, myogenesis, and glucose homeostasis. Chemerin message is regulated by nuclear receptor agonists, metabolic signaling proteins and intermediates, and proinflammatory cytokines. Following translation chemerin is secreted as an inactive pro-protein, and its secretion can be regulated depending on cell type. Chemerin bioactivity is largely dependent on carboxyl-terminal proteolytic processing and removal of inhibitory residues. Chemerin is abundant in human epidermis where it is well-placed to provide barrier protection. In host defense, chemerin plays dual roles as a broad spectrum antimicrobial protein and as a leukocyte attractant for macrophages, dendritic cells, and NK cells. Here we review the mechanisms underlying chemerin regulation and its function in host defense.

Insights from human studies into the host defense against candidiasis.

PubMed

Filler, Scott G

2012-04-01

Candida spp. are the most common cause of mucosal and disseminated fungal infections in humans. Studies using mutant strains of mice have provided initial information about the roles of dectin-1, CARD9, and Th17 cytokines in the host defense against candidiasis. Recent technological advances have resulted in the identification of mutations in specific genes that predispose humans to develop candidal infection. The analysis of individuals with these mutations demonstrates that dectin-1 is critical for the host defense against vulvovaginal candidiasis and candidal colonization of the gastrointestinal tract. They also indicate that CARD9 is important for preventing both mucosal and disseminated candidiasis, whereas the Th17 response is necessary for the defense against mucocutaneous candidiasis. This article reviews the recent studies of genetic defects in humans that result in an increased susceptibility to candidiasis and discusses how these studies provide new insight into the host defense against different types of candidal infections. Copyright © 2011 Elsevier Ltd. All rights reserved.

Use of experimental airborne infections for monitoring altered host defenses.

PubMed Central

Gardner, D E

1982-01-01

The success or failure of the respiratory system to defend itself against airborne infectious agents largely depends upon the efficiency of the pulmonary defenses to maintain sterility and to dispose of unwanted substances. Both specific and nonspecific host defenses cooperate in the removal and inactivation of such agents. Several studies have shown that these defenses are vulnerable to a wide range of environmental agents and that there is a good relationship between exposure to pollutant and the impaired resistance to pulmonary disease. There are numerous immunological, biochemical and physiological techniques that are routinely used to identify and to characterize individual impairments of these defenses. Based on these effects, various hypotheses are proposed as to what health consequences could be expected from these effects. The ultimate test is whether the host, with its compromised defense mechanisms, is still capable of sustaining the total injury and continuing to defend itself against opportunistic pathogens. This paper describes the use of an experimental airborne infectious disease model capable of predicting subtle changes in host defenses at concentrations below which there are any other overt toxicological effects. Such sensitivity is possible because the model measure not just a single "health" parameter, but instead is capable of reflecting the total responses caused by the test chemical. Images FIGURE 3. PMID:7060549

An orthologue of the host-defense protein psoriasin (S100A7) is expressed in frog skin.

PubMed

Matthijs, Severine; Hernalsteens, Jean-Pierre; Roelants, Kim

2017-02-01

Host-defense peptides and proteins are vital for first line protection against bacteria. Most host-defense peptides and proteins common in vertebrates have been studied primarily in mammals, while their orthologues in non-mammalian vertebrates received less attention. We found that the European Common Frog Rana temporaria expresses a protein in its skin that is evolutionarily related to the host-defense protein S100A7. This prompted us to test if the encoded protein, which is an important microbicidal protein in human skin, shows similar activity in frogs. The R. temporaria protein lacks the zinc-binding sites that are key to the antimicrobial activity of human S100A7 at neutral pH. However, despite being less potent, the R. temporaria protein does compromise bacterial membranes at low pH, similar to its human counterpart. We postulate that, while amphibian S100A7 likely serves other functions, the capacity to compromise bacterial cell membranes evolved early in tetrapod evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dectin-1 plays an important role in host defense against systemic Candida glabrata infection.

PubMed

Chen, Si Min; Shen, Hui; Zhang, Teng; Huang, Xin; Liu, Xiao Qi; Guo, Shi Yu; Zhao, Jing Jun; Wang, Chun Fang; Yan, Lan; Xu, Guo Tong; Jiang, Yuan Ying; An, Mao Mao

2017-11-17

Candida glabrata is the second most common pathogen of severe candidiasis in immunocompromised hosts, following C. albicans. Although C. glabrata and C. albicans belong to the same genus, they are phylogenetically distinct. C-type lectin receptors (CLRs), acting as pattern-recognition receptors (PRRs), play critical roles in host defense against C. albicans infections. However, our understanding of the specific roles of CLRs in host defense against C. glabrata is limited. Here, we explored the potential roles of the C-type lectins Dectin-1 and Dectin-2 in host defense against C. glabrata. We found that both Dectin-1-deficient mice (Dectin-1 -/- ) and Dectin-2-deficient mice (Dectin-2 -/- ) are more susceptible to C. glabrata infection. Dectin-1confers host higher sensitivity for sensing C. glabrata infections, while the effect of Dectin-2 in the host defense against C. glabrata is infection dose dependent. Dectin-1 is required for host myeloid cells recognition, killing of C. glabrata, and development of subsequent Th1 and Th17 cell-mediated adaptive immune response. Significantly impaired inflammatory responses such as inflammatory cells recruitment and cytokines release that were induced by C. glabrata were manifested in Dectin-1-deficient mice. Together, our study demonstrates that Dectin-1 plays an important role in host defense against systemic Candida glabrata infections, indicating a previous unknown control mechanism for this particular type of infection in host. Our study, therefore, provides new insights into the host defense against C. glabrata.

Invasive bark beetle-associated microbes degrade a host defensive monoterpene.

PubMed

Xu, Le-Tian; Lu, Min; Sun, Jiang-Hua

2016-04-01

Conifers respond to herbivore attack with defensive chemicals, which are toxic to both insects and their associated microorganisms. Microorganisms associated with insects have been widely reported to metabolize toxic chemicals, which may help both microorganisms and host insects overcome host conifer defense. Dendroctonus valens LeConte, an introduced exotic pest from North America to China, has killed millions of healthy pines. Alpha-pinene is the most abundant defensive monoterpene in Chinese Pinus tabuliformis. Although microorganisms associated with D. valens have already been investigated, little is known about their bioactivities when encountering host defensive monoterpenes. In this study, we evaluated the influences of different concentrations of α-pinene to D. valens and the three most frequently isolated yeasts and bacteria of D. valens, and further assayed microorganisms' capabilities to degrade α-pinene. Results showed that the gallery lengths and body weight changes of bark beetles were significantly affected by 6 mg/mL and 12 mg/mL of α-pinene applied in media compared to controls. The tolerance of experimental microorganisms to α-pinene varied depending on the microbial species. Two out of three yeast strains and all three bacterial strains degraded 20%-50% of α-pinene compared to controls in 24 h in vitro. The microorganisms capable of α-pinene degradation in vitro and their tolerance to high levels of α-pinene suggested that D. valens-associated microorganisms may help both microorganisms and the bark beetle overcome host α-pinene defense. © 2015 Institute of Zoology, Chinese Academy of Sciences.

Interaction between Pseudomonas aeruginosa and host defenses in cystic fibrosis.

PubMed

Marshall, B C; Carroll, K C

1991-03-01

The major causes of morbidity and mortality in cystic fibrosis are chronic pulmonary obstruction and infection. Mucoid Pseudomonas aeruginosa is the primary pathogen in up to 90% of these patients. Once Pseudomonas organisms colonize the airways, they are virtually never eradicated. No defect in systemic host defense has been elucidated, however, several mechanisms contribute to the breakdown in host defenses that allow persistence of this organism in the endobronchial space. These mechanisms involve both bacterial adaptation to an unfavorable host environment and impaired host response. P aeruginosa adapts to the host by expressing excessive mucoid exopolysaccharide and a less virulent form of lipopolysaccharide. These features make it less likely to cause systemic infection, yet still enable it to resist local host defenses. Mucociliary clearance becomes impaired due to abnormal viscoelastic properties of sputum, squamous metaplasia of the respiratory epithelium, and bronchiectasis. Despite a brisk antibody response to a variety of Pseudomonas antigens, several defects in antibody-mediated opsonophagocytosis have been identified. These include (1) development of antibody isotypes that are suboptimal at promoting phagocytosis, (2) formation of immune complexes that inhibit phagocytosis, and (3) proteolytic fragmentation of immunoglobulins in the endobronchial space. Complement-mediated opsonophagocytosis is also compromised by proteolytic cleavage of complement receptors from the cell surface of neutrophils and complement opsonins from the surface of Pseudomonas. The resultant chronic inflammation and infection lead to eventual obliteration of the airways.

Th17 cell cytokine secretion profile in host defense and autoimmunity.

PubMed

Graeber, Kristen E; Olsen, Nancy J

2012-02-01

The goal of this review is to examine the effector functions of Th17 cells in host defense and autoimmunity. Published literature on Th17 cells was reviewed with a focus on the secreted products that mediate effector activities of these cells. Th17 cells secrete an array of cytokines that contribute to host defense and that bridge the innate and adaptive arms of the immune response. When this subset of T cells is dysregulated, autoimmune phenomena develop that contribute to the manifestations of many autoimmune diseases. Th17 cells are positioned at a crossroads between innate and adaptive immunity and provide mediators that are essential for host defense. Current interest in harnessing this system for treatment of autoimmune disease will be challenged by the need to avoid abrogating these many protective functions.

The bacteriome-mycobiome interaction and antifungal host defense.

PubMed

Oever, Jaap Ten; Netea, Mihai G

2014-11-01

Large communities of microorganisms, collectively termed the microbiome, inhabit our body surfaces. With the advent of next-generation sequencing, the diversity and abundance of these communities are being unravelled. Besides an imporant role in metabolic processes, the microbiome is essential for proper functioning of our immune system, including the defense against fungi. Despite the progress of the past years, studies aimed at characterizing our fungal colonizers (the mycobiome) are limited; nevertheless fungi are important players of the microbiome, either as a cofactor in disease or as potential pathogens. In this review, we describe the role of the bacterial microbiome in antifungal host defense. On the one hand, bacteria provide colonization resistance to fungi, inhibit Candida virulence by preventing yeast-hyphal transition and contribute to epithelial integrity, all factors are important for the pathogenesis of invasive fungal disease. On the other hand, several bacterial species modulate mucosal (antifungal) immune responses. Murine studies demonstrate important effects of the microbiome on the antifungal responses of T-helper 17 cells, regulatory T cells and innate lymphoid cells. Inferred from these studies, perturbation of the healthy microbiome should be avoided and microbiome manipulation and interventions based on bacteria-derived pathways involved in immunomodulation are attractive options for modulating antifungal host defense. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evolution of Caenorhabditis elegans host defense under selection by the bacterial parasite Serratia marcescens.

PubMed

Penley, McKenna J; Ha, Giang T; Morran, Levi T

2017-01-01

Parasites can impose strong selection on hosts. In response, some host populations have adapted via the evolution of defenses that prevent or impede infection by parasites. However, host populations have also evolved life history shifts that maximize host fitness despite infection. Outcrossing and self-fertilization can have contrasting effects on evolutionary trajectories of host populations. While selfing and outcrossing are known to affect the rate at which host populations adapt in response to parasites, these mating systems may also influence the specific traits that underlie adaptation to parasites. Here, we determined the role of evolved host defense versus altered life history,in mixed mating (selfing and outcrossing) and obligately outcrossing C. elegans host populations after experimental evolution with the bacterial parasite, S. marcescens. Similar to previous studies, we found that both mixed mating and obligately outcrossing host populations adapted to S. marcescens exposure, and that the obligately outcrossing populations exhibited the greatest rates of adaptation. Regardless of the host population mating system, exposure to parasites did not significantly alter reproductive timing or total fecundity over the course of experimental evolution. However, both mixed mating and obligately outcrossing host populations exhibited significantly reduced mortality rates in the presence of the parasite after experimental evolution. Therefore, adaptation in both the mixed mating and obligately outcrossing populations was driven, at least in part, by the evolution of increased host defense and not changes in host life history. Thus, the host mating system altered the rate of adaptation, but not the nature of adaptive change in the host populations.

Evolution of Caenorhabditis elegans host defense under selection by the bacterial parasite Serratia marcescens

PubMed Central

Penley, McKenna J.; Ha, Giang T.; Morran, Levi T.

2017-01-01

Parasites can impose strong selection on hosts. In response, some host populations have adapted via the evolution of defenses that prevent or impede infection by parasites. However, host populations have also evolved life history shifts that maximize host fitness despite infection. Outcrossing and self-fertilization can have contrasting effects on evolutionary trajectories of host populations. While selfing and outcrossing are known to affect the rate at which host populations adapt in response to parasites, these mating systems may also influence the specific traits that underlie adaptation to parasites. Here, we determined the role of evolved host defense versus altered life history,in mixed mating (selfing and outcrossing) and obligately outcrossing C. elegans host populations after experimental evolution with the bacterial parasite, S. marcescens. Similar to previous studies, we found that both mixed mating and obligately outcrossing host populations adapted to S. marcescens exposure, and that the obligately outcrossing populations exhibited the greatest rates of adaptation. Regardless of the host population mating system, exposure to parasites did not significantly alter reproductive timing or total fecundity over the course of experimental evolution. However, both mixed mating and obligately outcrossing host populations exhibited significantly reduced mortality rates in the presence of the parasite after experimental evolution. Therefore, adaptation in both the mixed mating and obligately outcrossing populations was driven, at least in part, by the evolution of increased host defense and not changes in host life history. Thus, the host mating system altered the rate of adaptation, but not the nature of adaptive change in the host populations. PMID:28792961

Too much of a good thing: How modulating LTB4 actions restore host defense in homeostasis or disease.

PubMed

Brandt, Stephanie L; Serezani, C Henrique

2017-10-01

The ability to regulate inflammatory pathways and host defense mechanisms is critical for maintaining homeostasis and responding to infections and tissue injury. While unbalanced inflammation is detrimental to the host; inadequate inflammation might not provide effective signals required to eliminate pathogens. On the other hand, aberrant inflammation could result in organ damage and impair host defense. The lipid mediator leukotriene B 4 (LTB 4 ) is a potent neutrophil chemoattractant and recently, its role as a dominant molecule that amplifies many arms of phagocyte antimicrobial effector function has been unveiled. However, excessive LTB 4 production contributes to disease severity in chronic inflammatory diseases such as diabetes and arthritis, which could potentially be involved in poor host defense in these groups of patients. In this review we discuss the cellular and molecular programs elicited during LTB 4 production and actions on innate immunity host defense mechanisms as well as potential therapeutic strategies to improve host defense. Copyright © 2017 Elsevier Ltd. All rights reserved.

Listeria phospholipases subvert host autophagic defenses by stalling pre-autophagosomal structures

PubMed Central

Tattoli, Ivan; Sorbara, Matthew T; Yang, Chloe; Tooze, Sharon A; Philpott, Dana J; Girardin, Stephen E

2013-01-01

Listeria can escape host autophagy defense pathways through mechanisms that remain poorly understood. We show here that in epithelial cells, Listeriolysin (LLO)-dependent cytosolic escape of Listeria triggered a transient amino-acid starvation host response characterized by GCN2 phosphorylation, ATF3 induction and mTOR inhibition, the latter favouring a pro-autophagic cellular environment. Surprisingly, rapid recovery of mTOR signalling was neither sufficient nor necessary for Listeria avoidance of autophagic targeting. Instead, we observed that Listeria phospholipases PlcA and PlcB reduced autophagic flux and phosphatidylinositol 3-phosphate (PI3P) levels, causing pre-autophagosomal structure stalling and preventing efficient targeting of cytosolic bacteria. In co-infection experiments, wild-type Listeria protected PlcA/B-deficient bacteria from autophagy-mediated clearance. Thus, our results uncover a critical role for Listeria phospholipases C in the inhibition of autophagic flux, favouring bacterial escape from host autophagic defense. PMID:24162724

Consequences of interspecific variation in defenses and herbivore host choice for the ecology and evolution of Inga, a speciose rainforest tree.

PubMed

Coley, Phyllis D; Endara, María-José; Kursar, Thomas A

2018-06-01

We summarize work on a speciose Neotropical tree genus, Inga (Fabaceae), examining how interspecific variation in anti-herbivore defenses may have evolved, how defenses shape host choice by herbivores and how they might regulate community composition and influence species radiations. Defenses of expanding leaves include secondary metabolites, extrafloral nectaries, rapid leaf expansion, trichomes, and synchrony and timing of leaf production. These six classes of defenses are orthogonal, supporting independent evolutionary trajectories. Moreover, only trichomes show a phylogenetic signature, suggesting evolutionary lability in nearly all defenses. The interspecific diversity in secondary metabolite profiles does not arise from the evolution of novel compounds, but from novel combinations of common compounds, presumably due to changes in gene regulation. Herbivore host choice is determined by plant defensive traits, not host phylogeny. Neighboring plants escape each other's pests if their defenses differ enough, thereby enforcing the high local diversity typical of tropical forests. Related herbivores feed on hosts with similar defenses, implying that there are phylogenetic constraints placed on the herbivore traits that are associated with host use. Divergence in defensive traits among Inga appears to be driven by herbivore pressure. However, the lack of congruence between herbivore and host phylogeny suggests that herbivores are tracking defenses, choosing hosts based on traits for which they already have adaptations. There is, therefore, an asymmetry in the host-herbivore evolutionary arms race.

The C-terminal sequence of several human serine proteases encodes host defense functions.

PubMed

Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Walse, Björn; Svensson, Bo; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

2011-01-01

Serine proteases of the S1 family have maintained a common structure over an evolutionary span of more than one billion years, and evolved a variety of substrate specificities and diverse biological roles, involving digestion and degradation, blood clotting, fibrinolysis and epithelial homeostasis. We here show that a wide range of C-terminal peptide sequences of serine proteases, particularly from the coagulation and kallikrein systems, share characteristics common with classical antimicrobial peptides of innate immunity. Under physiological conditions, these peptides exert antimicrobial effects as well as immunomodulatory functions by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, selected peptides are protective against lipopolysaccharide-induced shock. Moreover, these S1-derived host defense peptides exhibit helical structures upon binding to lipopolysaccharide and also permeabilize liposomes. The results uncover new and fundamental aspects on host defense functions of serine proteases present particularly in blood and epithelia, and provide tools for the identification of host defense molecules of therapeutic interest. Copyright © 2011 S. Karger AG, Basel.

Chemical defense of early life stages of benthic marine invertebrates.

PubMed

Lindquist, Niels

2002-10-01

Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

Reed warbler hosts fine-tune their defenses to track three decades of cuckoo decline.

PubMed

Thorogood, Rose; Davies, Nicholas B

2013-12-01

Interactions between avian hosts and brood parasites can provide a model for how animals adapt to a changing world. Reed warbler (Acrocephalus scirpaceus) hosts employ costly defenses to combat parasitism by common cuckoos (Cuculus canorus). During the past three decades cuckoos have declined markedly across England, reducing parasitism at our study site (Wicken Fen) from 24% of reed warbler nests in 1985 to 1% in 2012. Here we show with experiments that host mobbing and egg rejection defenses have tracked this decline in local parasitism risk: the proportion of reed warbler pairs mobbing adult cuckoos (assessed by responses to cuckoo mounts and models) has declined from 90% to 38%, and the proportion rejecting nonmimetic cuckoo eggs (assessed by responses to model eggs) has declined from 61% to 11%. This is despite no change in response to other nest enemies or mimetic model eggs. Individual variation in both defenses is predicted by parasitism risk during the host's egg-laying period. Furthermore, the response of our study population to temporal variation in parasitism risk can also explain spatial variation in egg rejection behavior in other populations across Europe. We suggest that spatial and temporal variation in parasitism risk has led to the evolution of plasticity in reed warbler defenses. © 2013 The Authors. Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Herbivore Oral Secreted Bacteria Trigger Distinct Defense Responses in Preferred and Non-Preferred Host Plants.

PubMed

Wang, Jie; Chung, Seung Ho; Peiffer, Michelle; Rosa, Cristina; Hoover, Kelli; Zeng, Rensen; Felton, Gary W

2016-06-01

Insect symbiotic bacteria affect host physiology and mediate plant-insect interactions, yet there are few clear examples of symbiotic bacteria regulating defense responses in different host plants. We hypothesized that plants would induce distinct defense responses to herbivore- associated bacteria. We evaluated whether preferred hosts (horsenettle) or non-preferred hosts (tomato) respond similarly to oral secretions (OS) from the false potato beetle (FPB, Leptinotarsa juncta), and whether the induced defense triggered by OS was due to the presence of symbiotic bacteria in OS. Both horsenettle and tomato damaged by antibiotic (AB) treated larvae showed higher polyphenol oxidase (PPO) activity than those damaged by non-AB treated larvae. In addition, application of OS from AB treated larvae induced higher PPO activity compared with OS from non-AB treated larvae or water treatment. False potato beetles harbor bacteria that may provide abundant cues that can be recognized by plants and thus mediate corresponding defense responses. Among all tested bacterial isolates, the genera Pantoea, Acinetobacter, Enterobacter, and Serratia were found to suppress PPO activity in tomato, while only Pantoea sp. among these four isolates was observed to suppress PPO activity in horsenettle. The distinct PPO suppression caused by symbiotic bacteria in different plants was similar to the pattern of induced defense-related gene expression. Pantoea inoculated FPB suppressed JA-responsive genes and triggered a SA-responsive gene in both tomato and horsenettle. However, Enterobacter inoculated FPB eliminated JA-regulated gene expression and elevated SA-regulated gene expression in tomato, but did not show evident effects on the expression levels of horsenettle defense-related genes. These results indicate that suppression of plant defenses by the bacteria found in the oral secretions of herbivores may be a more widespread phenomenon than previously indicated.

Effects of parasite pressure on parasite mortality and reproductive output in a rodent-flea system: inferring host defense trade-offs.

PubMed

Warburton, Elizabeth M; Kam, Michael; Bar-Shira, Enav; Friedman, Aharon; Khokhlova, Irina S; Koren, Lee; Asfur, Mustafa; Geffen, Eli; Kiefer, Daniel; Krasnov, Boris R; Degen, A Allan

2016-09-01

Evaluating host resistance via parasite fitness helps place host-parasite relationships within evolutionary and ecological contexts; however, few studies consider both these processes simultaneously. We investigated how different levels of parasite pressure affect parasite mortality and reproductive success in relationship to host defense efforts, using the rodent Gerbillus nanus and the flea Xenopsylla conformis as a host-parasite system. Fifteen immune-naïve male rodents were infested with 20, 50, or 100 fleas for four weeks. During this time number of new imagoes produced per adult flea (our flea reproductive output metric), flea mortality, and change in circulating anti-flea immunoglobulin G (our measure of adaptive immune defense) were monitored. Three hypotheses guided this work: (1) increasing parasite pressure would heighten host defenses; (2) parasite mortality would increase and parasite reproductive output would decrease with increasing investment in host defense; and (3) hosts under high parasite pressure could invest in behavioral and/or immune responses. We predicted that at high infestation levels (a) parasite mortality would increase; (b) flea reproductive output per individual would decrease; and (c) host circulating anti-flea antibody levels would increase. The hypotheses were partially supported. Flea mortality significantly increased and flea reproductive output significantly decreased as flea pressure increased. Host adaptive immune defense did not significantly change with increasing flea pressure. Therefore, we inferred that investment in host behavioral defense, either alone or in combination with density-dependent effects, may be more efficient at increasing flea mortality and decreasing flea reproductive output than antibody production during initial infestation in this system.

DNA-sensing inflammasomes: regulation of bacterial host defense and the gut microbiota.

PubMed

Man, Si Ming; Karki, Rajendra; Kanneganti, Thirumala-Devi

2016-06-01

DNA sensors are formidable immune guardians of the host. At least 14 cytoplasmic DNA sensors have been identified in recent years, each with specialized roles in driving inflammation and/or cell death. Of these, AIM2 is a sensor of dsDNA, and forms an inflammasome complex to activate the cysteine protease caspase-1, mediates the release of the proinflammatory cytokines IL-1β and IL-18, and induces pyroptosis. The inflammasome sensor NLRP3 can also respond to DNA in the forms of oxidized mitochondrial DNA and the DNA derivative RNA:DNA hybrids produced by bacteria, whereas the putative inflammasome sensor IFI16 responds to viral DNA in the nucleus. Although inflammasomes provoke inflammation for anti-microbial host defense, they must also maintain homeostasis with commensal microbiota. Here, we outline recent advances highlighting the complex relationship between DNA-sensing inflammasomes, bacterial host defense and the gut microbiota. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reed Warbler Hosts Fine-Tune their Defenses to Track Three Decades of Cuckoo Decline

PubMed Central

Thorogood, Rose; Davies, Nicholas B

2013-01-01

Interactions between avian hosts and brood parasites can provide a model for how animals adapt to a changing world. Reed warbler (Acrocephalus scirpaceus) hosts employ costly defenses to combat parasitism by common cuckoos (Cuculus canorus). During the past three decades cuckoos have declined markedly across England, reducing parasitism at our study site (Wicken Fen) from 24% of reed warbler nests in 1985 to 1% in 2012. Here we show with experiments that host mobbing and egg rejection defenses have tracked this decline in local parasitism risk: the proportion of reed warbler pairs mobbing adult cuckoos (assessed by responses to cuckoo mounts and models) has declined from 90% to 38%, and the proportion rejecting nonmimetic cuckoo eggs (assessed by responses to model eggs) has declined from 61% to 11%. This is despite no change in response to other nest enemies or mimetic model eggs. Individual variation in both defenses is predicted by parasitism risk during the host’s egg-laying period. Furthermore, the response of our study population to temporal variation in parasitism risk can also explain spatial variation in egg rejection behavior in other populations across Europe. We suggest that spatial and temporal variation in parasitism risk has led to the evolution of plasticity in reed warbler defenses. PMID:24299407

Host Defense Peptide Resistance Contributes to Colonization and Maximal Intestinal Pathology by Crohn's Disease-Associated Adherent-Invasive Escherichia coli

PubMed Central

McPhee, Joseph B.; Small, Cherrie L.; Reid-Yu, Sarah A.; Brannon, John R.; Le Moual, Hervé

2014-01-01

Host defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associated Escherichia coli commonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasive E. coli (AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to α-helical cationic peptides and α- and β-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6, arlA, which encodes a Mig-14 family protein implicated in defensin resistance, and arlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut. PMID:24866805

Disentangling Detoxification: Gene Expression Analysis of Feeding Mountain Pine Beetle Illuminates Molecular-Level Host Chemical Defense Detoxification Mechanisms

PubMed Central

Robert, Jeanne A.; Pitt, Caitlin; Bonnett, Tiffany R.; Yuen, Macaire M. S.; Keeling, Christopher I.; Bohlmann, Jörg; Huber, Dezene P. W.

2013-01-01

The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae) that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq) of mountain pine beetle male and female adults either starved or fed in male-female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S-transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle. PMID:24223726

Disentangling detoxification: gene expression analysis of feeding mountain pine beetle illuminates molecular-level host chemical defense detoxification mechanisms.

PubMed

Robert, Jeanne A; Pitt, Caitlin; Bonnett, Tiffany R; Yuen, Macaire M S; Keeling, Christopher I; Bohlmann, Jörg; Huber, Dezene P W

2013-01-01

The mountain pine beetle, Dendroctonus ponderosae, is a native species of bark beetle (Coleoptera: Curculionidae) that caused unprecedented damage to the pine forests of British Columbia and other parts of western North America and is currently expanding its range into the boreal forests of central and eastern Canada and the USA. We conducted a large-scale gene expression analysis (RNA-seq) of mountain pine beetle male and female adults either starved or fed in male-female pairs for 24 hours on lodgepole pine host tree tissues. Our aim was to uncover transcripts involved in coniferophagous mountain pine beetle detoxification systems during early host colonization. Transcripts of members from several gene families significantly increased in insects fed on host tissue including: cytochromes P450, glucosyl transferases and glutathione S-transferases, esterases, and one ABC transporter. Other significantly increasing transcripts with potential roles in detoxification of host defenses included alcohol dehydrogenases and a group of unexpected transcripts whose products may play an, as yet, undiscovered role in host colonization by mountain pine beetle.

Chapter 13. Physiology and ecology of host defense against microbial invaders

USDA-ARS?s Scientific Manuscript database

Insects mount a complex hierarchy of defenses that pathogens must overcome before successful infection is achieved. Behavioral avoidance and antiseptic behaviors by host insects reduce the degree of encounters between the insect and pathogens. Any pathogen that contacts or establishes on a potentia...

Proteolytic Activation Transforms Heparin Cofactor II into a Host Defense Molecule

PubMed Central

Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Tollefsen, Douglas M.; Malmsten, Martin; Mörgelin, Matthias

2013-01-01

The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic. In this study, we demonstrate a previously unknown role for HCII in host defense. Proteolytic cleavage of the molecule induced a conformational change, thereby inducing endotoxin-binding and antimicrobial properties. Analyses employing representative peptide epitopes mapped these effects to helices A and D. Mice deficient in HCII showed increased susceptibility to invasive infection by Pseudomonas aeruginosa, along with a significantly increased cytokine response. Correspondingly, decreased levels of HCII were observed in wild-type animals challenged with bacteria or endotoxin. In humans, proteolytically cleaved HCII forms were detected during wounding and in association with bacteria. Thus, the protease-induced uncovering of cryptic epitopes in HCII, which transforms the molecule into a host defense factor, represents a previously unknown regulatory mechanism in HCII biology and innate immunity. PMID:23656734

Proteolytic activation transforms heparin cofactor II into a host defense molecule.

PubMed

Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Tollefsen, Douglas M; Malmsten, Martin; Mörgelin, Matthias; Schmidtchen, Artur

2013-06-15

The abundant serine proteinase inhibitor heparin cofactor II (HCII) has been proposed to inhibit extravascular thrombin. However, the exact physiological role of this plasma protein remains enigmatic. In this study, we demonstrate a previously unknown role for HCII in host defense. Proteolytic cleavage of the molecule induced a conformational change, thereby inducing endotoxin-binding and antimicrobial properties. Analyses employing representative peptide epitopes mapped these effects to helices A and D. Mice deficient in HCII showed increased susceptibility to invasive infection by Pseudomonas aeruginosa, along with a significantly increased cytokine response. Correspondingly, decreased levels of HCII were observed in wild-type animals challenged with bacteria or endotoxin. In humans, proteolytically cleaved HCII forms were detected during wounding and in association with bacteria. Thus, the protease-induced uncovering of cryptic epitopes in HCII, which transforms the molecule into a host defense factor, represents a previously unknown regulatory mechanism in HCII biology and innate immunity.

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.

Dead bacteria reverse antibiotic-induced host defense impairment in burns.

PubMed

Chen, Lee-Wei; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei

2014-10-01

Burn patients can incur high rates of hospital-acquired infections. The mechanism of antibiotic exposure on inducing infection vulnerability has not been determined. This study aimed to examine the effects of antibiotic treatment on host defense mechanisms. First we treated C57/BL6 mice with combined antibiotic treatment after 30% to 35% total body surface area burn. Animals were sacrificed at 48 hours after sham or thermal injury treatment. Bacterial counts in intestinal lumen and mucosa were measured. Next, we treated animals with or without oral dead Escherichia coli or Staphylococcus aureus supplementation to stimulate Toll-like receptor in the intestinal mucosa. Toll-like receptor 4, antibacterial protein expression, nuclear factor (NF)-κB DNA-binding activity, and bacteria-killing activity in the intestinal mucosa; intestinal permeability; bacterial translocation to mesenteric lymph nodes; Klebsiella pneumoniae translocation; interleukin-6 in the blood; and phagocytic activity of alveolar macrophages, were assessed. Thermal injury increased microflora and NF-κB DNA-binding activity of the intestine. Systemic antibiotic treatment decreased gut microflora and increased bacterial translocation to mesenteric lymph nodes, intestinal permeability, and interleukin-6 levels in the blood. Antibiotic treatment also decreased bacteria-killing activity in intestinal mucosa and phagocytic activity of alveolar macrophages. Oral dead E coli and S aureus supplementation induced NF-κB DNA-binding activity, Toll-like receptor 4, and antibacterial protein expression of the intestinal mucosa. Taken together with the fact that dead bacteria reversed antibiotic-induced K pneumoniae translocation and intestinal and pulmonary defense impairment, we conclude that combined antibiotic treatment results in systemic host defense impairment in burns through the decrease in intestinal flora. We suggest that dead bacteria supplementation could induce nondefensin protein expression and

The Phytophthora cactorum genome provides insights into the adaptation to host defense compounds and fungicides.

PubMed

Yang, Min; Duan, Shengchang; Mei, Xinyue; Huang, Huichuan; Chen, Wei; Liu, Yixiang; Guo, Cunwu; Yang, Ting; Wei, Wei; Liu, Xili; He, Xiahong; Dong, Yang; Zhu, Shusheng

2018-04-25

Phytophthora cactorum is a homothallic oomycete pathogen, which has a wide host range and high capability to adapt to host defense compounds and fungicides. Here we report the 121.5 Mb genome assembly of the P. cactorum using the third-generation single-molecule real-time (SMRT) sequencing technology. It is the second largest genome sequenced so far in the Phytophthora genera, which contains 27,981 protein-coding genes. Comparison with other Phytophthora genomes showed that P. cactorum had a closer relationship with P. parasitica, P. infestans and P. capsici. P. cactorum has similar gene families in the secondary metabolism and pathogenicity-related effector proteins compared with other oomycete species, but specific gene families associated with detoxification enzymes and carbohydrate-active enzymes (CAZymes) underwent expansion in P. cactorum. P. cactorum had a higher utilization and detoxification ability against ginsenosides-a group of defense compounds from Panax notoginseng-compared with the narrow host pathogen P. sojae. The elevated expression levels of detoxification enzymes and hydrolase activity-associated genes after exposure to ginsenosides further supported that the high detoxification and utilization ability of P. cactorum play a crucial role in the rapid adaptability of the pathogen to host plant defense compounds and fungicides.

Trans-suppression of defense DEFB1 gene in intestinal epithelial cells following Cryptosporidium parvum infection is associated with host delivery of parasite Cdg7_FLc_1000 RNA.

PubMed

Ming, Zhenping; Gong, Ai-Yu; Wang, Yang; Zhang, Xin-Tian; Li, Min; Dolata, Courtney E; Chen, Xian-Ming

2018-03-01

To counteract host immunity, Cryptosporidium parvum has evolved multiple strategies to suppress host antimicrobial defense. One such strategy is to reduce the production of the antimicrobial peptide beta-defensin 1 (DEFB1) by host epithelial cells but the underlying mechanisms remain unclear. Recent studies demonstrate that a panel of parasite RNA transcripts of low protein-coding potential are delivered into infected host cells and may modulate host gene transcription. Using in vitro models of intestinal cryptosporidiosis, in this study, we analyzed the expression profile of host beta-defensin genes in host cells following infection. We found that C. parvum infection caused a significant downregulation of the DEFB1 gene. Interestingly, downregulation of DEFB1 gene was associated with host delivery of Cdg7_FLc_1000 RNA transcript, a C. parvum RNA that has previously demonstrated to be delivered into the nuclei of infected host cells. Knockdown of Cdg7_FLc_1000 in host cells could attenuate the trans-suppression of host DEFB1 gene and decreased the parasite burden. Therefore, our data suggest that trans-suppression of DEFB1 gene in intestinal epithelial cells following C. parvum infection involves host delivery of parasite Cdg7_FLc_1000 RNA, a process that may be relevant to the epithelial defense evasion by C. parvum at the early stage of infection.

Acute radiation syndrome (ARS) - treatment of the reduced host defense.

PubMed

Heslet, Lars; Bay, Christiane; Nepper-Christensen, Steen

2012-01-01

The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes. Review of the current literature. The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage's important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS. Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least <2 Gy by prompt dosing of 250-400 μg GM-CSF/m(2) or 5 μg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF < 300 mcg per day for at least 14-21 days. The present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary

Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections.

PubMed

Findlay, Fern; Proudfoot, Lorna; Stevens, Craig; Barlow, Peter G

2016-01-01

Cationic Host Defense Peptides (HDP, also known as antimicrobial peptides) are crucial components of the innate immune system and possess broad-spectrum antibacterial, antiviral, and immunomodulatory activities. They can contribute to the rapid clearance of biological agents through direct killing of the organisms, inhibition of pro-inflammatory mediators such as lipopolysaccharide, and by modulating the inflammatory response to infection. Category A biological agents and materials, as classified by the United States National Institutes for Health, the US Centers for Disease Control and Prevention, and the US Department of Homeland Security, carry the most severe threat in terms of human health, transmissibility, and preparedness. As such, there is a pressing need for novel frontline approaches for prevention and treatment of diseases caused by these organisms, and exploiting the broad antimicrobial activity exhibited by cationic host defense peptides represents an exciting priority area for clinical research. This review will summarize what is known about the antimicrobial and antiviral effects of the two main families of cationic host defense peptides, cathelicidins, and defensins in the context of Category A biological agents which include, but are not limited to; anthrax (Bacillus anthracis), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis). In addition, we highlight priority areas, particularly emerging viral infections, where more extensive research is urgently required.

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.

Peroxidasin contributes to lung host defense by direct binding and killing of gram-negative bacteria.

PubMed

Shi, Ruizheng; Cao, Zehong; Li, Hong; Graw, Jochen; Zhang, Guogang; Thannickal, Victor J; Cheng, Guangjie

2018-05-01

Innate immune recognition is classically mediated by the interaction of host pattern-recognition receptors and pathogen-associated molecular patterns; this triggers a series of downstream signaling events that facilitate killing and elimination of invading pathogens. In this report, we provide the first evidence that peroxidasin (PXDN; also known as vascular peroxidase-1) directly binds to gram-negative bacteria and mediates bactericidal activity, thus, contributing to lung host defense. PXDN contains five leucine-rich repeats and four immunoglobulin domains, which allows for its interaction with lipopolysaccharide, a membrane component of gram-negative bacteria. Bactericidal activity of PXDN is mediated via its capacity to generate hypohalous acids. Deficiency of PXDN results in a failure to eradicate Pseudomonas aeruginosa and increased mortality in a murine model of Pseudomonas lung infection. These observations indicate that PXDN mediates previously unrecognized host defense functions against gram-negative bacterial pathogens.

Microbial pathogens trigger host DNA double-strand breaks whose abundance is reduced by plant defense responses.

PubMed

Song, Junqi; Bent, Andrew F

2014-04-01

Immune responses and DNA damage repair are two fundamental processes that have been characterized extensively, but the links between them remain largely unknown. We report that multiple bacterial, fungal and oomycete plant pathogen species induce double-strand breaks (DSBs) in host plant DNA. DNA damage detected by histone γ-H2AX abundance or DNA comet assays arose hours before the disease-associated necrosis caused by virulent Pseudomonas syringae pv. tomato. Necrosis-inducing paraquat did not cause detectable DSBs at similar stages after application. Non-pathogenic E. coli and Pseudomonas fluorescens bacteria also did not induce DSBs. Elevation of reactive oxygen species (ROS) is common during plant immune responses, ROS are known DNA damaging agents, and the infection-induced host ROS burst has been implicated as a cause of host DNA damage in animal studies. However, we found that DSB formation in Arabidopsis in response to P. syringae infection still occurs in the absence of the infection-associated oxidative burst mediated by AtrbohD and AtrbohF. Plant MAMP receptor stimulation or application of defense-activating salicylic acid or jasmonic acid failed to induce a detectable level of DSBs in the absence of introduced pathogens, further suggesting that pathogen activities beyond host defense activation cause infection-induced DNA damage. The abundance of infection-induced DSBs was reduced by salicylic acid and NPR1-mediated defenses, and by certain R gene-mediated defenses. Infection-induced formation of γ-H2AX still occurred in Arabidopsis atr/atm double mutants, suggesting the presence of an alternative mediator of pathogen-induced H2AX phosphorylation. In summary, pathogenic microorganisms can induce plant DNA damage. Plant defense mechanisms help to suppress rather than promote this damage, thereby contributing to the maintenance of genome integrity in somatic tissues.

Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery.

PubMed

Wang, Li-Fong; Lin, You-Sheng; Huang, Nan-Chieh; Yu, Chia-Yi; Tsai, Wei-Lun; Chen, Jih-Jung; Kubota, Toru; Matsuoka, Mayumi; Chen, Siang-Ru; Yang, Chih-Shiang; Lu, Ruo-Wei; Lin, Yi-Ling; Chang, Tsung-Hsien

2015-03-01

Hydroxychloroquine (HCQ) is an antimalarial drug also used in treating autoimmune diseases. Its antiviral activity was demonstrated in restricting HIV infection in vitro; however, the clinical implications remain controversial. Infection with dengue virus (DENV) is a global public health problem, and we lack an antiviral drug for DENV. Here, we evaluated the anti-DENV potential of treatment with HCQ. Immunofluorescence assays demonstrated that HCQ could inhibit DENV serotype 1-4 infection in vitro. RT-qPCR analysis of HCQ-treated cells showed induced expression of interferon (IFN)-related antiviral proteins and certain inflammatory cytokines. Mechanistic study suggested that HCQ activated the innate immune signaling pathways of IFN-β, AP-1, and NFκB. Knocking down mitochondrial antiviral signaling protein (MAVS), inhibiting TANK binding kinase 1 (TBK1)/inhibitor-κB kinase ɛ (IKKɛ), and blocking type I IFN receptor reduced the efficiency of HCQ against DENV-2 infection. Furthermore, HCQ significantly induced cellular production of reactive oxygen species (ROS), which was involved in the host defense system. Suppression of ROS production attenuated the innate immune activation and anti-DENV-2 effect of HCQ. In summary, HCQ triggers the host defense machinery by inducing ROS- and MAVS-mediated innate immune activation against DENV infection and may be a candidate drug for DENV infection.

Early Birds in Korea: Exporting Defense AT and L Has Far Reaching Impact

DTIC Science & Technology

2015-11-01

studying the Defense AT&L magazine published for the U.S. Depart-ment of Defense (DoD) by the Defense Acquisition University (DAU). The study club’s...April Publications of the Early Birds Study group draw information and inspiration from Defense AT&L magazine . Collage of Early Birds Study Group...study club name. The club established two main objectives: (1) study the De- fense AT&L magazine published in English to learn advanced defense

Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

PubMed Central

Netea, Mihai G.; Mouton, Johan W.; Melchers, Willem J. G.; Verweij, Paul E.; de Hoog, G. Sybren

2014-01-01

SUMMARY Among the melanized fungi, the so-called “black yeasts” and their filamentous relatives are particularly significant as agents of severe phaeohyphomycosis, chromoblastomycosis, and mycetoma in humans and animals. The pathogenicity and virulence of these fungi may differ significantly between closely related species. The factors which probably are of significance for pathogenicity include the presence of melanin and carotene, formation of thick cell walls and meristematic growth, presence of yeast-like phases, thermo- and perhaps also osmotolerance, adhesion, hydrophobicity, assimilation of aromatic hydrocarbons, and production of siderophores. Host defense has been shown to rely mainly on the ingestion and elimination of fungal cells by cells of the innate immune system, especially neutrophils and macrophages. However, there is increasing evidence supporting a role of T-cell-mediated immune responses, with increased interleukin-10 (IL-10) and low levels of gamma interferon (IFN-γ) being deleterious during the infection. There are no standardized therapies for treatment. It is therefore important to obtain in vitro susceptibilities of individual patients' fungal isolates in order to provide useful information for selection of appropriate treatment protocols. This article discusses the pathogenesis and host defense factors for these fungi and their severity, chronicity, and subsequent impact on treatment and prevention of diseases in human or animal hosts. PMID:24982320

Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections

PubMed Central

Findlay, Fern; Proudfoot, Lorna; Stevens, Craig

2016-01-01

Cationic Host Defense Peptides (HDP, also known as antimicrobial peptides) are crucial components of the innate immune system and possess broad-spectrum antibacterial, antiviral, and immunomodulatory activities. They can contribute to the rapid clearance of biological agents through direct killing of the organisms, inhibition of pro-inflammatory mediators such as lipopolysaccharide, and by modulating the inflammatory response to infection. Category A biological agents and materials, as classified by the United States National Institutes for Health, the US Centers for Disease Control and Prevention, and the US Department of Homeland Security, carry the most severe threat in terms of human health, transmissibility, and preparedness. As such, there is a pressing need for novel frontline approaches for prevention and treatment of diseases caused by these organisms, and exploiting the broad antimicrobial activity exhibited by cationic host defense peptides represents an exciting priority area for clinical research. This review will summarize what is known about the antimicrobial and antiviral effects of the two main families of cationic host defense peptides, cathelicidins, and defensins in the context of Category A biological agents which include, but are not limited to; anthrax (Bacillus anthracis), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis). In addition, we highlight priority areas, particularly emerging viral infections, where more extensive research is urgently required. PMID:27315342

A RECENT HOST RANGE EXPANSION IN JUNONIA COENIA HÜBNER (NYMPHALIDAE): OVIPOSITION PREFERENCE, SURVIVAL, GROWTH, AND CHEMICAL DEFENSE.

PubMed

Camara, Mark D

1997-06-01

This paper reports on an investigation of two populations of Junonia coenia, the buckeye butterfly, one that feeds on the species' typical host plant (Plantago lanceolata) and one that utilizes a novel host plant (Kickxia elatine). I examined these populations for local adaptive responses in terms of oviposition behavior, growth, and chemical defense, on both P. lanceolata and K. elatine. In addition, I examined the genetic architecture underlying these traits using a full-sib quantitative genetic analysis. I found that a significant majority of females prefer the host plant species found at their collection sites in oviposition tests, but that there is no evidence that they are locally adapted in growth performance, as measured by fifth-instar and pupal weights and development times. Neither are there correlations between oviposition preferences of females and the growth performance or levels of chemical defense of their offspring. The two populations studied do, however, show specialization in terms of the levels of chemical defense they sequester from their host plants. I argue that these results indicate that natural enemies are the normal barriers to host range expansion in this oligophagous herbivore because a breakdown in those barriers results in genetic changes that enhance resistance to predation. This is despite the fact that adaptive responses in physiology are unlikely to be limited by a lack of genetic variability; the genetic architecture among traits would be conducive to specialization in growth performance; and there are costs to chemical defense in this species. All these conditions would tend to argue that J. coenia harbors considerable potential for coevolutionary interactions with its chemically defended hosts, but this potential is not realized, probably because natural selection on diet breadth by natural enemies is much stronger than selection from host plants in this system. © 1997 The Society for the Study of Evolution.

Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-Mediated Oxidative Antimicrobial Offense.

PubMed

Wiemann, Philipp; Perevitsky, Adi; Lim, Fang Yun; Shadkchan, Yana; Knox, Benjamin P; Landero Figueora, Julio A; Choera, Tsokyi; Niu, Mengyao; Steinberger, Andrew J; Wüthrich, Marcel; Idol, Rachel A; Klein, Bruce S; Dinauer, Mary C; Huttenlocher, Anna; Osherov, Nir; Keller, Nancy P

2017-05-02

The Fenton-chemistry-generating properties of copper ions are considered a potent phagolysosome defense against pathogenic microbes, yet our understanding of underlying host/microbe dynamics remains unclear. We address this issue in invasive aspergillosis and demonstrate that host and fungal responses inextricably connect copper and reactive oxygen intermediate (ROI) mechanisms. Loss of the copper-binding transcription factor AceA yields an Aspergillus fumigatus strain displaying increased sensitivity to copper and ROI in vitro, increased intracellular copper concentrations, decreased survival in challenge with murine alveolar macrophages (AMΦs), and reduced virulence in a non-neutropenic murine model. ΔaceA survival is remediated by dampening of host ROI (chemically or genetically) or enhancement of copper-exporting activity (CrpA) in A. fumigatus. Our study exposes a complex host/microbe multifactorial interplay that highlights the importance of host immune status and reveals key targetable A. fumigatus counter-defenses. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effects of elicitors of host plant defenses on pear psylla (Cacopsylla pyricola: Psyllidae)

USDA-ARS?s Scientific Manuscript database

Pear psylla, Cacopsylla pyricola (Foerster) (Hemiptera: Psyllidae), is a key pest of cultivated pear (Pyrus communis L.) in North America and Europe. We examined the effects of foliar applications of three commercially available chemical elicitors of host-plant defenses, Actigard, Employ, and ODC, ...

Is the pathogenic ergot fungus a conditional defensive mutualist for its host grass?

PubMed

Wäli, Pauliina P; Wäli, Piippa R; Saikkonen, Kari; Tuomi, Juha

2013-01-01

It is well recognized, that outcomes of mutualistic plant-microorganism interactions are often context dependent and can range from mutualistic to antagonistic depending on conditions. Instead, seemingly pathogenic associations are generally considered only harmful to plants. The ergot fungus (Claviceps purpurea) is a common seed pathogen of grasses and cereals. Ergot sclerotia contain alkaloids which can cause severe toxicity in mammals when ingested, and thus the fungal infection might provide protection for the host plant against mammalian herbivores. Theoretically, the net effect of ergot infection would positively affect host seed set if the cost is not too high and the defensive effect is strong enough. According to our empirical data, this situation is plausible. First, we found no statistically significant seed loss in wild red fescue (Festuca rubra) inflorescences due to ergot infection, but the seed succession decreased along increasing number of sclerotia. Second, in a food choice experiment, sheep showed avoidance against forage containing ergot. Third, the frequency of ergot-infected inflorescences was higher in sheep pastures than surrounding ungrazed areas, indicating a protective effect against mammalian grazing. We conclude that, although ergot can primarily be categorized as a plant pathogen, ergot infection may sometimes represent indirect beneficial effects for the host plant. Ergot may thus serve as a conditional defensive mutualist for its host grass, and the pathogenic interaction may range from antagonistic to mutualistic depending on the situation.

Obligate Biotroph Pathogens of the Genus Albugo Are Better Adapted to Active Host Defense Compared to Niche Competitors

PubMed Central

Ruhe, Jonas; Agler, Matthew T.; Placzek, Aleksandra; Kramer, Katharina; Finkemeier, Iris; Kemen, Eric M.

2016-01-01

Recent research suggested that plants behave differently under combined versus single abiotic and biotic stress conditions in controlled environments. While this work has provided a glimpse into how plants might behave under complex natural conditions, it also highlights the need for field experiments using established model systems. In nature, diverse microbes colonize the phyllosphere of Arabidopsis thaliana, including the obligate biotroph oomycete genus Albugo, causal agent of the common disease white rust. Biotrophic, as well as hemibiotrophic plant pathogens are characterized by efficient suppression of host defense responses. Lab experiments have even shown that Albugo sp. can suppress non-host resistance, thereby enabling otherwise avirulent pathogen growth. We asked how a pathogen that is vitally dependent on a living host can compete in nature for limited niche space while paradoxically enabling colonization of its host plant for competitors? To address this question, we used a proteomics approach to identify differences and similarities between lab and field samples of Albugo sp.-infected and -uninfected A. thaliana plants. We could identify highly similar apoplastic proteomic profiles in both infected and uninfected plants. In wild plants, however, a broad range of defense-related proteins were detected in the apoplast regardless of infection status, while no or low levels of defense-related proteins were detected in lab samples. These results indicate that Albugo sp. do not strongly affect immune responses and leave distinct branches of the immune signaling network intact. To validate our findings and to get mechanistic insights, we tested a panel of A. thaliana mutant plants with induced or compromised immunity for susceptibility to different biotrophic pathogens. Our findings suggest that the biotroph pathogen Albugo selectively interferes with host defense under different environmental and competitive pressures to maintain its ecological niche

Avian Antimicrobial Host Defense Peptides: From Biology to Therapeutic Applications

PubMed Central

Zhang, Guolong; Sunkara, Lakshmi T.

2014-01-01

Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomoduatory properties. Because they act on the microbial membranes or host immune cells, HDPs pose a low risk of triggering microbial resistance and therefore, are being actively investigated as a novel class of antimicrobials and vaccine adjuvants. Cathelicidins and β-defensins are two major families of HDPs in avian species. More than a dozen HDPs exist in birds, with the genes in each HDP family clustered in a single chromosomal segment, apparently as a result of gene duplication and diversification. In contrast to their mammalian counterparts that adopt various spatial conformations, mature avian cathelicidins are mostly α-helical. Avian β-defensins, on the other hand, adopt triple-stranded β-sheet structures similar to their mammalian relatives. Besides classical β-defensins, a group of avian-specific β-defensin-related peptides, namely ovodefensins, exist with a different six-cysteine motif. Like their mammalian counterparts, avian cathelicidins and defensins are derived from either myeloid or epithelial origin expressed in a majority of tissues with broad-spectrum antibacterial and immune regulatory activities. Structure-function relationship studies with several avian HDPs have led to identification of the peptide analogs with potential for use as antimicrobials and vaccine adjuvants. Dietary modulation of endogenous HDP synthesis has also emerged as a promising alternative approach to disease control and prevention in chickens. PMID:24583933

Interplay between Herpesvirus Infection and Host Defense by PML Nuclear Bodies.

PubMed

Tavalai, Nina; Stamminger, Thomas

2009-12-01

In recent studies we and others have identified the cellular proteins PML, hDaxx, and Sp100, which form a subnuclear structure known as nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs), as host restriction factors that counteract herpesviral infections by inhibiting viral replication at different stages. The antiviral function of ND10, however, is antagonized by viral regulatory proteins (e.g., ICP0 of herpes simplex virus; IE1 of human cytomegalovirus) which induce either a modification or disruption of ND10. This review will summarize the current knowledge on how viral replication is inhibited by ND10 proteins. Furthermore, herpesviral strategies to defeat this host defense mechanism are discussed.

Alaskan Air Defense and Early Warning Systems Clear Air ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Alaskan Air Defense and Early Warning Systems - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP.

PubMed

Spanò, Stefania; Gao, Xiang; Hannemann, Sebastian; Lara-Tejero, María; Galán, Jorge E

2016-02-10

Cell-autonomous defense mechanisms are potent strategies that protect individual cells against intracellular pathogens. The Rab-family GTPase Rab32 was previously shown to restrict the intracellular human pathogen Salmonella Typhi, but its potential broader role in antimicrobial defense remains unknown. We show that Rab32 represents a general cell-autonomous, antimicrobial defense that is counteracted by two Salmonella effectors. Mice lacking Rab-32 or its nucleotide exchange factor BLOC-3 are permissive to S. Typhi infection and exhibit increased susceptibility to S. Typhimurium. S. Typhimurium counters this defense pathway by delivering two type III secretion effectors, SopD2, a Rab32 GAP, and GtgE, a specific Rab32 protease. An S. Typhimurium mutant strain lacking these two effectors exhibits markedly reduced virulence, which is fully restored in BLOC-3-deficient mice. These results demonstrate that a cell-autonomous, Rab32-dependent host defense pathway plays a central role in the defense against vacuolar pathogens and describe a mechanism evolved by a bacterial pathogen to counter it. Copyright © 2016 Elsevier Inc. All rights reserved.

Is the Pathogenic Ergot Fungus a Conditional Defensive Mutualist for Its Host Grass?

PubMed Central

Wäli, Pauliina P.; Wäli, Piippa R.; Saikkonen, Kari; Tuomi, Juha

2013-01-01

It is well recognized, that outcomes of mutualistic plant-microorganism interactions are often context dependent and can range from mutualistic to antagonistic depending on conditions. Instead, seemingly pathogenic associations are generally considered only harmful to plants. The ergot fungus (Claviceps purpurea) is a common seed pathogen of grasses and cereals. Ergot sclerotia contain alkaloids which can cause severe toxicity in mammals when ingested, and thus the fungal infection might provide protection for the host plant against mammalian herbivores. Theoretically, the net effect of ergot infection would positively affect host seed set if the cost is not too high and the defensive effect is strong enough. According to our empirical data, this situation is plausible. First, we found no statistically significant seed loss in wild red fescue (Festuca rubra) inflorescences due to ergot infection, but the seed succession decreased along increasing number of sclerotia. Second, in a food choice experiment, sheep showed avoidance against forage containing ergot. Third, the frequency of ergot-infected inflorescences was higher in sheep pastures than surrounding ungrazed areas, indicating a protective effect against mammalian grazing. We conclude that, although ergot can primarily be categorized as a plant pathogen, ergot infection may sometimes represent indirect beneficial effects for the host plant. Ergot may thus serve as a conditional defensive mutualist for its host grass, and the pathogenic interaction may range from antagonistic to mutualistic depending on the situation. PMID:23874924

Toxoplasma gondii TgIST co-opts host chromatin repressors dampening STAT1-dependent gene regulation and IFN-γ–mediated host defenses

PubMed Central

Brenier-Pinchart, Marie-Pierre; Bertini, Rose-Laurence; Varesano, Aurélie; De Bock, Pieter-Jan

2016-01-01

An early hallmark of Toxoplasma gondii infection is the rapid control of the parasite population by a potent multifaceted innate immune response that engages resident and homing immune cells along with pro- and counter-inflammatory cytokines. In this context, IFN-γ activates a variety of T. gondii–targeting activities in immune and nonimmune cells but can also contribute to host immune pathology. T. gondii has evolved mechanisms to timely counteract the host IFN-γ defenses by interfering with the transcription of IFN-γ–stimulated genes. We now have identified TgIST (T. gondii inhibitor of STAT1 transcriptional activity) as a critical molecular switch that is secreted by intracellular parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent proinflammatory gene expression. We show that TgIST not only sequesters STAT1 on dedicated loci but also promotes shaping of a nonpermissive chromatin through its capacity to recruit the nucleosome remodeling deacetylase (NuRD) transcriptional repressor. We found that during mice acute infection, TgIST-deficient parasites are rapidly eliminated by the homing Gr1+ inflammatory monocytes, thus highlighting the protective role of TgIST against IFN-γ–mediated killing. By uncovering TgIST functions, this study brings novel evidence on how T. gondii has devised a molecular weapon of choice to take control over a ubiquitous immune gene expression mechanism in metazoans, as a way to promote long-term parasitism. PMID:27503074

The Role of Dectin-2 for Host Defense Against Disseminated Candidiasis.

PubMed

Ifrim, Daniela C; Quintin, Jessica; Courjol, Flavie; Verschueren, Ineke; van Krieken, J Han; Koentgen, Frank; Fradin, Chantal; Gow, Neil A R; Joosten, Leo A B; van der Meer, Jos W M; van de Veerdonk, Frank; Netea, Mihai G

2016-04-01

Despite the fact that Candida albicans is an important human fungal pathogen and Dectin-2 is a major pattern recognition receptor for fungi, our knowledge regarding the role of Dectin-2 for the host defense against disseminated candidiasis is limited. Dectin-2 deficient (Dectin-2(-/-)) mice were more susceptible to systemic candidiasis, and the susceptibility was mirrored by an elevated fungal load in the kidneys that correlated with the presence of large inflammatory foci. Phagocytosis of Candida by the macrophages lacking the Dectin-2 receptor was moderately decreased, while production of most of the macrophage-derived cytokines from Dectin-2(-/-) mice with systemic candidiasis was decreased. No striking differences among several Candida mutants defective in mannans could be detected between naïve wild-type and Dectin-2(-/-) mice, apart from the β-mannan-deficient bmt1Δ/bmt2Δ/bmt5Δ triple mutant, suggesting that β-mannan may partially mask α-mannan detection, which is the major fungal structure recognized by Dectin-2. Deciphering the mechanisms responsible for host defense against the majority of C. albicans strains represents an important step in understanding the pathophysiology of systemic candidiasis, which might lead to the development of novel immunotherapeutic strategies.

IgE and mast cells in host defense against parasites and venoms

PubMed Central

Mukai, Kaori; Tsai, Mindy; Galli, Stephen J.

2016-01-01

IgE-dependent mast cell activation is a major effector mechanism underlying the pathology associated with allergic disorders. The most dramatic of these IgE-associated disorders is the fatal anaphylaxis which can occur in some people who have developed IgE antibodies to otherwise innocuous antigens, such as those contained in certain foods and medicines. Why would such a highly “maladaptive” immune response develop in evolution, and be retained to the present day? Host defense against parasites has long been considered the only beneficial function that might be conferred by IgE and mast cells. However, recent studies have provided evidence that, in addition to participating in host resistance to certain parasites, mast cells and IgE are critical components of innate (mast cells) and adaptive (mast cells and IgE) immune responses that can enhance host defense against the toxicity of certain arthropod and animal venoms, including enhancing the survival of mice injected with such venoms. Yet, in some people, developing IgE antibodies to insect or snake venoms puts them at risk for having a potentially fatal anaphylactic reaction upon subsequent exposure to such venoms. Delineating the mechanisms underlying beneficial versus detrimental innate and adaptive immune responses associated with mast cell activation and IgE is likely to enhance our ability to identify potential therapeutic targets in such settings, not only for reducing the pathology associated with allergic disorders but perhaps also for enhancing immune protection against pathogens and animal venoms. PMID:27225312

IgE and mast cells in host defense against parasites and venoms.

PubMed

Mukai, Kaori; Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J

2016-09-01

IgE-dependent mast cell activation is a major effector mechanism underlying the pathology associated with allergic disorders. The most dramatic of these IgE-associated disorders is the fatal anaphylaxis which can occur in some people who have developed IgE antibodies to otherwise innocuous antigens, such as those contained in certain foods and medicines. Why would such a highly "maladaptive" immune response develop in evolution and be retained to the present day? Host defense against parasites has long been considered the only beneficial function that might be conferred by IgE and mast cells. However, recent studies have provided evidence that, in addition to participating in host resistance to certain parasites, mast cells and IgE are critical components of innate (mast cells) and adaptive (mast cells and IgE) immune responses that can enhance host defense against the toxicity of certain arthropod and animal venoms, including enhancing the survival of mice injected with such venoms. Yet, in some people, developing IgE antibodies to insect or snake venoms puts them at risk for having a potentially fatal anaphylactic reaction upon subsequent exposure to such venoms. Delineating the mechanisms underlying beneficial versus detrimental innate and adaptive immune responses associated with mast cell activation and IgE is likely to enhance our ability to identify potential therapeutic targets in such settings, not only for reducing the pathology associated with allergic disorders but perhaps also for enhancing immune protection against pathogens and animal venoms.

Butyrate enhances disease resistance of chickens by inducing antimicrobial host defense peptide gene expression

USDA-ARS?s Scientific Manuscript database

Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. I...

Host Defense Versus Immunosuppression: Unisexual Infection With Male or Female Schistosoma mansoni Differentially Impacts the Immune Response Against Invading Cercariae.

PubMed

Sombetzki, Martina; Koslowski, Nicole; Rabes, Anne; Seneberg, Sonja; Winkelmann, Franziska; Fritzsche, Carlos; Loebermann, Micha; Reisinger, Emil C

2018-01-01

Infection with the intravascular diecious trematode Schistosoma spp . remains a serious tropical disease and public health problem in the developing world, affecting over 258 million people worldwide. During chronic Schistosoma mansoni infection, complex immune responses to tissue-entrapped parasite eggs provoke granulomatous inflammation which leads to serious damage of the liver and intestine. The suppression of protective host immune mechanisms by helminths promotes parasite survival and benefits the host by reducing tissue damage. However, immune-suppressive cytokines may reduce vaccine-induced immune responses. By combining a single-sex infection system with a murine air pouch model, we were able to demonstrate that male and female schistosomes play opposing roles in modulating the host's immune response. Female schistosomes suppress early innate immune responses to invading cercariae in the skin and upregulate anergy-associated genes. In contrast, male schistosomes trigger strong innate immune reactions which lead to a reduction in worm and egg burden in the liver. Our data suggest that the female worm is a neglected player in the dampening of the host's immune defense system and is therefore a promising target for new immune modulatory therapies.

Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae.

PubMed

Samuelson, Derrick R; Shellito, Judd E; Maffei, Vincent J; Tague, Eric D; Campagna, Shawn R; Blanchard, Eugene E; Luo, Meng; Taylor, Christopher M; Ronis, Martin J J; Molina, Patricia E; Welsh, David A

2017-06-01

Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis). To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole) via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls) liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control) animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein. Collectively, these

Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae

PubMed Central

Campagna, Shawn R.; Blanchard, Eugene E.; Ronis, Martin J. J.

2017-01-01

Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis). To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole) via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls) liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control) animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein. Collectively, these

Helicobacter pylori Persistence: an Overview of Interactions between H. pylori and Host Immune Defenses

PubMed Central

Algood, Holly M. Scott; Cover, Timothy L.

2006-01-01

Helicobacter pylori is a gram-negative bacterium that persistently colonizes more than half of the global human population. In order to successfully colonize the human stomach, H. pylori must initially overcome multiple innate host defenses. Remarkably, H. pylori can persistently colonize the stomach for decades or an entire lifetime despite development of an acquired immune response. This review focuses on the immune response to H. pylori and the mechanisms by which H. pylori resists immune clearance. Three main sections of the review are devoted to (i) analysis of the immune response to H. pylori in humans, (ii) analysis of interactions of H. pylori with host immune defenses in animal models, and (iii) interactions of H. pylori with immune cells in vitro. The topics addressed in this review are important for understanding how H. pylori resists immune clearance and also are relevant for understanding the pathogenesis of diseases caused by H. pylori (peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma). PMID:17041136

Inducible defense against pathogens and parasites: optimal choice among multiple options.

PubMed

Shudo, E; Iwasa, Y

2001-03-21

Defense against pathogen, parasites and herbivores is often enhanced after their invasion into the host's body. Sometimes different options are adopted depending on the identity and the quantity of the pathogen, exemplified by the switch between Th1 and Th2 systems in mammalian immunity. In this paper, we study the optimal defense of the host when two alternative responses are available, which differ in the effectiveness of suppressing the growth of pathogen (parasite, or herbivore), the damage to the host caused by the defense response, and the magnitude of time delay before the defense response becomes fully effective. The optimal defense is the one that minimizes the sum of the damages caused by the pathogen and the cost due to defense activities. The damage by pathogens increases in proportion to the time integral of the pathogen abundance, and the cost is proportional to the defense activity. We can prove that a single globally optimal combination of defense options always exists and there is no other local optimum. Depending on the parameters, the optimal is to adopt only the early response, only the late response, or both responses. The defense response with a shorter time delay is more heavily used when the pathogen grows fast, the initial pathogen abundance is large, and the difference in time delay is long. We also study the host's optimal choice between constitutive and inducible defenses. In the constitutive defense, the response to pathogen attack works without delay, but it causes the cost even when the pathogen attack does not occur. We discuss mammalian immunity and the plant chemical defense from the model's viewpoint. Copyright 2001 Academic Press.

Host plant invests in growth rather than chemical defense when attacked by a specialist herbivore.

PubMed

Arab, Alberto; Trigo, José Roberto

2011-05-01

Plant defensive compounds may be a cost rather than a benefit when plants are attacked by specialist insects that may overcome chemical barriers by strategies such as sequestering plant compounds. Plants may respond to specialist herbivores by compensatory growth rather than chemical defense. To explore the use of defensive chemistry vs. compensatory growth we studied Brugmansia suaveolens (Solanaceae) and the specialist larvae of the ithomiine butterfly Placidina euryanassa, which sequester defensive tropane alkaloids (TAs) from this host plant. We investigated whether the concentration of TAs in B. suaveolens was changed by P. euryanassa damage, and whether plants invest in growth, when damaged by the specialist. Larvae feeding during 24 hr significantly decreased TAs in damaged plants, but they returned to control levels after 15 days without damage. Damaged and undamaged plants did not differ significantly in leaf area after 15 days, indicating compensatory growth. Our results suggest that B. suaveolens responds to herbivory by the specialist P. euryanassa by investing in growth rather than chemical defense.

Localization and developmental expression of two chicken host defense peptides: cathelicidin-2 and avian β-defensin 9.

PubMed

Cuperus, Tryntsje; van Dijk, Albert; Dwars, R Marius; Haagsman, Henk P

2016-08-01

In the first weeks of life young chickens are highly susceptible to infectious diseases due to immaturity of the immune system. Little is known about the expression of host defense peptides (HDPs) during this period. In this study we examined the expression pattern of two chicken HDPs, the cathelicidin CATH-2 and the β-defensin AvBD9 by immunohistochemistry in a set of organs from embryonic day 12 until four weeks posthatch. AvBD9 was predominantly found in enteroendocrine cells throughout the intestine, the first report of in vivo HDP expression in this cell type, and showed stable expression levels during development. CATH-2 was exclusively found in heterophils which decreased after hatch in most of the examined organs including spleen, bursa and small intestine. In the lung CATH-2 expression was biphasic and peaked at the first day posthatch. In short, CATH-2 and AvBD9 appear to be expressed in cell types strategically located to respond to infectious stimuli, suggesting these peptides play a role in embryonic and early posthatch defense. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early-Season Host Switching in Adelphocoris spp. (Hemiptera: Miridae) of Differing Host Breadth

PubMed Central

Pan, Hongsheng; Lu, Yanhui; Wyckhuys, Kris A. G.

2013-01-01

The mirid bugs Adelphocoris suturalis (Jakovlev), Adelphocoris lineolatus (Goeze) and Adelphocoris fasciaticollis (Reuter) (Hemiptera: Miridae) are common pests of several agricultural crops. These three species have vastly different geographical distributions, phenologies and abundances, all of which are linked to their reliance on local plants. Previous work has shown notable differences in Adelphocoris spp. host use for overwintering. In this study, we assessed the extent to which each of the Adelphocoris spp. relies on some of its major overwinter hosts for spring development. Over the course of four consecutive years (2009–2012), we conducted population surveys on 77 different plant species from 39 families. During the spring, A. fasciaticollis used the broadest range of hosts, as it was found on 35 plant species, followed by A. suturalis (15 species) and A. lineolatus (7 species). Abundances of the species greatly differed between host plants, with A. fasciaticollis reaching the highest abundance on Chinese date (Ziziphus jujuba Mill.), whereas both A. suturalis and A. lineolatus preferred alfalfa (Medicago sativa L.). The host breadths of the three Adelphocoris spp. differed greatly between subsequent spring and winter seasons. The generalist species exhibited the least host fidelity, with A. suturalis and A. lineolatus using 8 of 22 and 4 of 12 overwinter host species for spring development, respectively. By contrast, the comparative specialist A. fasciaticollis relied on 9 of its 11 overwinter plants as early-season hosts. We highlight important seasonal changes in host breadth and interspecific differences in the extent of host switching behavior between the winter and spring seasons. These findings benefit our understanding of the evolutionary interactions between mirid bugs and their host plants and can be used to guide early-season population management. PMID:23527069

Parasitism by Cuscuta pentagona attenuates host plant defenses against insect herbivores.

PubMed

Runyon, Justin B; Mescher, Mark C; De Moraes, Consuelo M

2008-03-01

Considerable research has examined plant responses to concurrent attack by herbivores and pathogens, but the effects of attack by parasitic plants, another important class of plant-feeding organisms, on plant defenses against other enemies has not been explored. We investigated how attack by the parasitic plant Cuscuta pentagona impacted tomato (Solanum lycopersicum) defenses against the chewing insect beet armyworm (Spodoptera exigua; BAW). In response to insect feeding, C. pentagona-infested (parasitized) tomato plants produced only one-third of the antiherbivore phytohormone jasmonic acid (JA) produced by unparasitized plants. Similarly, parasitized tomato, in contrast to unparasitized plants, failed to emit herbivore-induced volatiles after 3 d of BAW feeding. Although parasitism impaired antiherbivore defenses, BAW growth was slower on parasitized tomato leaves. Vines of C. pentagona did not translocate JA from BAW-infested plants: amounts of JA in parasite vines grown on caterpillar-fed and control plants were similar. Parasitized plants generally contained more salicylic acid (SA), which can inhibit JA in some systems. Parasitized mutant (NahG) tomato plants deficient in SA produced more JA in response to insect feeding than parasitized wild-type plants, further suggesting cross talk between the SA and JA defense signaling pathways. However, JA induction by BAW was still reduced in parasitized compared to unparasitized NahG, implying that other factors must be involved. We found that parasitized plants were capable of producing induced volatiles when experimentally treated with JA, indicating that resource depletion by the parasite does not fully explain the observed attenuation of volatile response to herbivore feeding. Collectively, these findings show that parasitic plants can have important consequences for host plant defense against herbivores.

Dual RNA-seq reveals no plastic transcriptional response of the coccidian parasite Eimeria falciformis to host immune defenses.

PubMed

Ehret, Totta; Spork, Simone; Dieterich, Christoph; Lucius, Richard; Heitlinger, Emanuel

2017-09-05

Parasites can either respond to differences in immune defenses that exist between individual hosts plastically or, alternatively, follow a genetically canalized ("hard wired") program of infection. Assuming that large-scale functional plasticity would be discernible in the parasite transcriptome we have performed a dual RNA-seq study of the lifecycle of Eimeria falciformis using infected mice with different immune status as models for coccidian infections. We compared parasite and host transcriptomes (dual transcriptome) between naïve and challenge infected mice, as well as between immune competent and immune deficient ones. Mice with different immune competence show transcriptional differences as well as differences in parasite reproduction (oocyst shedding). Broad gene categories represented by differently abundant host genes indicate enrichments for immune reaction and tissue repair functions. More specifically, TGF-beta, EGF, TNF and IL-1 and IL-6 are examples of functional annotations represented differently depending on host immune status. Much in contrast, parasite transcriptomes were neither different between Coccidia isolated from immune competent and immune deficient mice, nor between those harvested from naïve and challenge infected mice. Instead, parasite transcriptomes have distinct profiles early and late in infection, characterized largely by biosynthesis or motility associated functional gene groups, respectively. Extracellular sporozoite and oocyst stages showed distinct transcriptional profiles and sporozoite transcriptomes were found enriched for species specific genes and likely pathogenicity factors. We propose that the niche and host-specific parasite E. falciformis uses a genetically canalized program of infection. This program is likely fixed in an evolutionary process rather than employing phenotypic plasticity to interact with its host. This in turn might limit the potential of the parasite to adapt to new host species or niches, forcing

Plant parasitic nematode effectors target host defense and nuclear functions to establish feeding cells.

PubMed

Quentin, Michaëel; Abad, Pierre; Favery, Bruno

2013-01-01

Plant parasitic nematodes are microscopic worms, the most damaging species of which have adopted a sedentary lifestyle within their hosts. These obligate endoparasites have a biotrophic relationship with plants, in which they induce the differentiation of root cells into hypertrophied, multinucleate feeding cells (FCs). Effectors synthesized in the esophageal glands of the nematode are injected into the plant cells via the syringe-like stylet and play a key role in manipulating the host machinery. The establishment of specialized FCs requires these effectors to modulate many aspects of plant cell morphogenesis and physiology, including defense responses. This cell reprogramming requires changes to host nuclear processes. Some proteins encoded by parasitism genes target host nuclei. Several of these proteins were immunolocalized within FC nuclei or shown to interact with host nuclear proteins. Comparative genomics and functional analyses are gradually revealing the roles of nematode effectors. We describe here these effectors and their hypothesized roles in the unique feeding behavior of these pests.

Feeding on Host Plants with Different Concentrations and Structures of Pyrrolizidine Alkaloids Impacts the Chemical-Defense Effectiveness of a Specialist Herbivore

PubMed Central

Cunha, Beatriz P.; Solferini, Vera N.

2015-01-01

Sequestration of chemical defenses from host plants is a strategy widely used by herbivorous insects to avoid predation. Larvae of the arctiine moth Utetheisa ornatrix feeding on unripe seeds and leaves of many species of Crotalaria (Leguminosae) sequester N-oxides of pyrrolizidine alkaloids (PAs) from these host plants, and transfer them to adults through the pupal stage. PAs confer protection against predation on all life stages of U. ornatrix. As U. ornatrix also uses other Crotalaria species as host plants, we evaluated whether the PA chemical defense against predation is independent of host plant use. We fed larvae from hatching to pupation with either leaves or seeds of one of eight Crotalaria species (C. incana, C. juncea, C. micans, C. ochroleuca, C. pallida, C. paulina, C. spectabilis, and C. vitellina), and tested if adults were preyed upon or released by the orb-weaving spider Nephila clavipes. We found that the protection against the spider was more effective in adults whose larvae fed on seeds, which had a higher PA concentration than leaves. The exceptions were adults from larvae fed on C. paulina, C. spectabilis and C. vitellina leaves, which showed high PA concentrations. With respect to the PA profile, we describe for the first time insect-PAs in U. ornatrix. These PAs, biosynthesized from the necine base retronecine of plant origin, or monocrotaline- and senecionine-type PAs sequestered from host plants, were equally active in moth chemical defense, in a dose-dependent manner. These results are also partially explained by host plant phylogeny, since PAs of the host plants do have a phylogenetic signal (clades with high and low PA concentrations in leaves) which is reflected in the adult defense. PMID:26517873

Feeding on Host Plants with Different Concentrations and Structures of Pyrrolizidine Alkaloids Impacts the Chemical-Defense Effectiveness of a Specialist Herbivore.

PubMed

Martins, Carlos H Z; Cunha, Beatriz P; Solferini, Vera N; Trigo, José R

2015-01-01

Sequestration of chemical defenses from host plants is a strategy widely used by herbivorous insects to avoid predation. Larvae of the arctiine moth Utetheisa ornatrix feeding on unripe seeds and leaves of many species of Crotalaria (Leguminosae) sequester N-oxides of pyrrolizidine alkaloids (PAs) from these host plants, and transfer them to adults through the pupal stage. PAs confer protection against predation on all life stages of U. ornatrix. As U. ornatrix also uses other Crotalaria species as host plants, we evaluated whether the PA chemical defense against predation is independent of host plant use. We fed larvae from hatching to pupation with either leaves or seeds of one of eight Crotalaria species (C. incana, C. juncea, C. micans, C. ochroleuca, C. pallida, C. paulina, C. spectabilis, and C. vitellina), and tested if adults were preyed upon or released by the orb-weaving spider Nephila clavipes. We found that the protection against the spider was more effective in adults whose larvae fed on seeds, which had a higher PA concentration than leaves. The exceptions were adults from larvae fed on C. paulina, C. spectabilis and C. vitellina leaves, which showed high PA concentrations. With respect to the PA profile, we describe for the first time insect-PAs in U. ornatrix. These PAs, biosynthesized from the necine base retronecine of plant origin, or monocrotaline- and senecionine-type PAs sequestered from host plants, were equally active in moth chemical defense, in a dose-dependent manner. These results are also partially explained by host plant phylogeny, since PAs of the host plants do have a phylogenetic signal (clades with high and low PA concentrations in leaves) which is reflected in the adult defense.

Oncolytic activities of host defense peptides.

PubMed

Al-Benna, Sammy; Shai, Yechiel; Jacobsen, Frank; Steinstraesser, Lars

2011-01-01

Cancer continues to be a leading source of morbidity and mortality worldwide in spite of progress in oncolytic therapies. In addition, the incidence of cancers affecting the breast, kidney, prostate and skin among others continue to rise. Chemotherapeutic drugs are widely used in cancer treatment but have the serious drawback of nonspecific toxicity because these agents target any rapidly dividing cell without discriminating between healthy and malignant cells. In addition, many neoplasms eventually become resistant to conventional chemotherapy due to selection for multidrug-resistant variants. The limitations associated with existing chemotherapeutic drugs have stimulated the search for new oncolytic therapies. Host defense peptides (HDPs) may represent a novel family of oncolytic agents that can avoid the shortcomings of conventional chemotherapy because they exhibit selective cytotoxicity against a broad spectrum of malignant human cells, including multi-drug-resistant neoplastic cells. Oncolytic activity by HDPs is usually via necrosis due to cell membrane lysis, but some HDPs can trigger apoptosis in cancer cells via mitochondrial membrane disruption. In addition, certain HDPs are anti-angiogenic which may inhibit cancer progression. This paper reviews oncolytic HDP studies in order to address the suitability of selected HDPs as oncolytic therapies.

Natural killer cells in host defense against veterinary pathogens.

PubMed

Shekhar, Sudhanshu; Yang, Xi

2015-11-15

Natural Killer (NK) cells constitute a major subset of innate lymphoid cells that do not express the T- and B-cell receptors and play an important role in antimicrobial defense. NK cells not only induce early and rapid innate immune responses, but also communicate with dendritic cells to shape the adaptive immunity, thus bridging innate and adaptive immunity. Although the functional biology of NK cells is well-documented in a variety of infections in humans and mice, their role in protecting domestic animals from infectious agents is only beginning to be understood. In this article, we summarize the current state of knowledge about the contribution of NK cells in pathogen defense in domestic animals, especially cattle and pigs. Understanding the immunobiology of NK cells will translate into strategies to manipulate these cells for preventive and therapeutic purposes. Copyright © 2015 Elsevier B.V. All rights reserved.

Platelets Mediate Host Defense against Staphylococcus aureus through Direct Bactericidal Activity and by Enhancing Macrophage Activities.

PubMed

Ali, Ramadan A; Wuescher, Leah M; Dona, Keith R; Worth, Randall G

2017-01-01

Platelets are the chief effector cells in hemostasis. However, recent evidence suggests they have multiple roles in host defense against infection. Reports by us and others showed that platelets functionally contribute to protection against Staphylococcus aureus infection. In the current study, the capacity of mouse platelets to participate in host defense against S. aureus infection was determined by assessing two possibilities. First, we determined the ability of platelets to kill S. aureus directly; and, second, we tested the possibility that platelets enhance macrophage phagocytosis and intracellular killing of S. aureus In this study we report evidence in support of both mechanisms. Platelets effectively killed two different strains of S. aureus. A clinical isolate of methicillin-resistant S. aureus was killed by platelets (>40% killing in 2 h) in a thrombin-dependent manner whereas a methicillin-sensitive strain was killed to equal extent but did not require thrombin. Interestingly, thrombin-stimulated platelets also significantly enhanced peritoneal macrophage phagocytosis of both methicillin-resistant S. aureus and methicillin-sensitive S. aureus by >70%, and restricted intracellular growth by >40%. Enhancement of macrophage anti-S. aureus activities is independent of contact with platelets but is mediated through releasable products, namely IL-1β. These data confirm our hypothesis that platelets participate in host defense against S. aureus both through direct killing of S. aureus and enhancing the antimicrobial function of macrophages in protection against S. aureus infection. Copyright © 2016 by The American Association of Immunologists, Inc.

Herbivore Diet Breadth and Host Plant Defense Mediate the Tri-Trophic Effects of Plant Toxins on Multiple Coccinellid Predators.

PubMed

Katsanis, Angelos; Rasmann, Sergio; Mooney, Kailen A

2016-01-01

Host plant defenses are known to cascade up food chains to influence herbivores and their natural enemies, but how herbivore and predator traits and identity mediate such tri-trophic dynamics is largely unknown. We assessed the influence of plant defense on aphid and coccinellid performance in laboratory trials with low- vs. high-glucosinolate varieties of Brassica napus, a dietary specialist (Brevicoryne brassicae) and generalist (Myzus persicae) aphid, and five species of aphidophagous coccinellids. The performance of the specialist and generalist aphids was similar and unaffected by variation in plant defense. Aphid glucosinolate concentration and resistance to predators differed by aphid species and host plant defense, and these effects acted independently. With respect to aphid species, the dietary generalist aphid (vs. specialist) had 14% lower glucosinolate concentration and coccinellid predators ate three-fold more aphids. With respect to host plant variety, the high-glucosinolate plants (vs. low) increased aphid glucosinolate concentration by 21%, but had relatively weak effects on predation by coccinellids and these effects varied among coccinellid species. In turn, coccinellid performance was influenced by the interactive effects of plant defense and aphid species, as the cascading, indirect effect of plant defense was greater when feeding upon the specialist than generalist aphid. When feeding upon specialist aphids, low- (vs. high-) glucosinolate plants increased coccinellid mass gain by 78% and accelerated development by 14%. In contrast, when feeding upon generalist aphids, low- (vs. high-) glucosinolate plants increased coccinellid mass gain by only 11% and had no detectable effect on development time. These interactive effects of plant defense and aphid diet breadth on predator performance also varied among coccinellid species; the indirect negative effects of plant defenses on predator performance was consistent among the five predators when

Signal Integration by the IκB Protein Pickle Shapes Drosophila Innate Host Defense.

PubMed

Morris, Otto; Liu, Xi; Domingues, Celia; Runchel, Christopher; Chai, Andrea; Basith, Shaherin; Tenev, Tencho; Chen, Haiyang; Choi, Sangdun; Pennetta, Giuseppa; Buchon, Nicolas; Meier, Pascal

2016-09-14

Pattern recognition receptors are activated following infection and trigger transcriptional programs important for host defense. Tight regulation of NF-κB activation is critical to avoid detrimental and misbalanced responses. We describe Pickle, a Drosophila nuclear IκB that integrates signaling inputs from both the Imd and Toll pathways by skewing the transcriptional output of the NF-κB dimer repertoire. Pickle interacts with the NF-κB protein Relish and the histone deacetylase dHDAC1, selectively repressing Relish homodimers while leaving other NF-κB dimer combinations unscathed. Pickle's ability to selectively inhibit Relish homodimer activity contributes to proper host immunity and organismal health. Although loss of pickle results in hyper-induction of Relish target genes and improved host resistance to pathogenic bacteria in the short term, chronic inactivation of pickle causes loss of immune tolerance and shortened lifespan. Pickle therefore allows balanced immune responses that protect from pathogenic microbes while permitting the establishment of beneficial commensal host-microbe relationships. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular characterization of the host defense activity of the barrier to autointegration factor against vaccinia virus.

PubMed

Ibrahim, Nouhou; Wicklund, April; Wiebe, Matthew S

2011-11-01

The barrier to autointegration factor (BAF) is an essential cellular protein with functions in mitotic nuclear reassembly, retroviral preintegration complex stability, and transcriptional regulation. Molecular properties of BAF include the ability to bind double-stranded DNA in a sequence-independent manner, homodimerize, and bind proteins containing a LEM domain. These capabilities allow BAF to compact DNA and assemble higher-order nucleoprotein complexes, the nature of which is poorly understood. Recently, it was revealed that BAF also acts as a potent host defense against poxviral DNA replication in the cytoplasm. Here, we extend these observations by examining the molecular mechanism through which BAF acts as a host defense against vaccinia virus replication and cytoplasmic DNA in general. Interestingly, BAF rapidly relocalizes to transfected DNA from a variety of sources, demonstrating that BAF's activity as a host defense factor is not limited to poxviral infection. BAF's relocalization to cytoplasmic foreign DNA is highly dependent upon its DNA binding and dimerization properties but does not appear to require its LEM domain binding activity. However, the LEM domain protein emerin is recruited to cytoplasmic DNA in a BAF-dependent manner during both transfection and vaccinia virus infection. Finally, we demonstrate that the DNA binding and dimerization capabilities of BAF are essential for its function as an antipoxviral effector, while the presence of emerin is not required. Together, these data provide further mechanistic insight into which of BAF's molecular properties are employed by cells to impair the replication of poxviruses or respond to foreign DNA in general.

Systemic Adenosine Triphosphate Impairs Neutrophil Chemotaxis and Host Defense in Sepsis.

PubMed

Li, Xiaoou; Kondo, Yutaka; Bao, Yi; Staudenmaier, Laura; Lee, Albert; Zhang, Jingping; Ledderose, Carola; Junger, Wolfgang G

2017-01-01

Sepsis remains an unresolved clinical problem. Therapeutic strategies focusing on inhibition of neutrophils (polymorphonuclear neutrophils) have failed, which indicates that a more detailed understanding of the underlying pathophysiology of sepsis is required. Polymorphonuclear neutrophil activation and chemotaxis require cellular adenosine triphosphate release via pannexin-1 channels that fuel autocrine feedback via purinergic receptors. In the current study, we examined the roles of endogenous and systemic adenosine triphosphate on polymorphonuclear neutrophil activation and host defense in sepsis. Prospective randomized animal investigation and in vitro studies. Preclinical academic research laboratory. Wild-type C57BL/6 mice, pannexin-1 knockout mice, and healthy human subjects used to obtain polymorphonuclear neutrophils for in vitro studies. Wild-type and pannexin-1 knockout mice were treated with suramin or apyrase to block the endogenous or systemic effects of adenosine triphosphate. Mice were subjected to cecal ligation and puncture and polymorphonuclear neutrophil activation (CD11b integrin expression), organ (liver) injury (plasma aspartate aminotransferase), bacterial spread, and survival were monitored. Human polymorphonuclear neutrophils were used to study the effect of systemic adenosine triphosphate and apyrase on chemotaxis. Inhibiting endogenous adenosine triphosphate reduced polymorphonuclear neutrophil activation and organ injury, but increased the spread of bacteria and mortality in sepsis. By contrast, removal of systemic adenosine triphosphate improved bacterial clearance and survival in sepsis by improving polymorphonuclear neutrophil chemotaxis. Systemic adenosine triphosphate impairs polymorphonuclear neutrophil functions by disrupting the endogenous purinergic signaling mechanisms that regulate cell activation and chemotaxis. Removal of systemic adenosine triphosphate improves polymorphonuclear neutrophil function and host defenses

Two host cytoplasmic effectors are required for pathogenesis of Phytophthora sojae by suppression of host defenses.

PubMed

Liu, Tingli; Ye, Wenwu; Ru, Yanyan; Yang, Xinyu; Gu, Biao; Tao, Kai; Lu, Shan; Dong, Suomeng; Zheng, Xiaobo; Shan, Weixing; Wang, Yuanchao; Dou, Daolong

2011-01-01

Phytophthora sojae encodes hundreds of putative host cytoplasmic effectors with conserved FLAK motifs following signal peptides, termed crinkling- and necrosis-inducing proteins (CRN) or Crinkler. Their functions and mechanisms in pathogenesis are mostly unknown. Here, we identify a group of five P. sojae-specific CRN-like genes with high levels of sequence similarity, of which three are putative pseudogenes. Functional analysis shows that the two functional genes encode proteins with predicted nuclear localization signals that induce contrasting responses when expressed in Nicotiana benthamiana and soybean (Glycine max). PsCRN63 induces cell death, while PsCRN115 suppresses cell death elicited by the P. sojae necrosis-inducing protein (PsojNIP) or PsCRN63. Expression of CRN fragments with deleted signal peptides and FLAK motifs demonstrates that the carboxyl-terminal portions of PsCRN63 or PsCRN115 are sufficient for their activities. However, the predicted nuclear localization signal is required for PsCRN63 to induce cell death but not for PsCRN115 to suppress cell death. Furthermore, silencing of the PsCRN63 and PsCRN115 genes in P. sojae stable transformants leads to a reduction of virulence on soybean. Intriguingly, the silenced transformants lose the ability to suppress host cell death and callose deposition on inoculated plants. These results suggest a role for CRN effectors in the suppression of host defense responses.

S1P dependent inter organ trafficking of group 2 innate lymphoid cells suppots host defense

USDA-ARS?s Scientific Manuscript database

Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a...

Host Defense Proteins in Breast Milk and Neonatal Yeast Colonization.

PubMed

Chow, Brian D W; Reardon, Juliann L; Perry, Emily O; Laforce-Nesbitt, Sonia S; Tucker, Richard; Bliss, Joseph M

2016-02-01

Colonization increases risk for invasive candidiasis in neonates. Breast milk host defense proteins may affect yeast colonization of infants. This study aimed to evaluate breast milk host defense proteins relative to yeast colonization in infants. Infants admitted for longer than 72 hours to the neonatal intensive care unit at Women & Infants Hospital in Providence, Rhode Island, were eligible. After consent, expressed breast milk and swabs from oral, rectal, and inguinal sites from infants were cultured weekly for 12 weeks, or until discharge, transfer, or death. Breast milk was tested for levels of human lactoferrin, lysozyme, apolipoprotein J, mucin-1, dermcidin, and soluble CD14 using commercial ELISA. Concentrations of these components were compared in breast milk received by infants who were colonized or not colonized with yeast. From an original cohort of 130, 61 infants had samples available for this subanalysis. A convenience sample of stored breast milk was analyzed. Median lactoferrin, apolipoprotein J, and mucin-1 did not differ between colonized and uncolonized groups. Soluble CD14 was higher in the surface-colonized group (1.8 μg/mL, n = 12) compared with the surface-uncolonized group (1.6 μg/mL, n = 12, P = .02). Median lysozyme levels were higher in the surface-uncolonized group (483.0 ng/mL, n = 12) versus the surface-colonized group (298.3 ng/mL, n = 12, P = .04). Median dermcidin levels were higher in the surface-uncolonized group (19.4 ng/mL, n = 12) versus the surface-colonized group (8.7 ng/mL, n = 12, P = .04). This study shows an association between colonization with Candida in neonates and lower levels of lysozyme and dermcidin in received breast milk. Further study is needed to confirm these findings. © The Author(s) 2015.

Parasitism by Cuscuta pentagona Attenuates Host Plant Defenses against Insect Herbivores1

PubMed Central

Runyon, Justin B.; Mescher, Mark C.; De Moraes, Consuelo M.

2008-01-01

Considerable research has examined plant responses to concurrent attack by herbivores and pathogens, but the effects of attack by parasitic plants, another important class of plant-feeding organisms, on plant defenses against other enemies has not been explored. We investigated how attack by the parasitic plant Cuscuta pentagona impacted tomato (Solanum lycopersicum) defenses against the chewing insect beet armyworm (Spodoptera exigua; BAW). In response to insect feeding, C. pentagona-infested (parasitized) tomato plants produced only one-third of the antiherbivore phytohormone jasmonic acid (JA) produced by unparasitized plants. Similarly, parasitized tomato, in contrast to unparasitized plants, failed to emit herbivore-induced volatiles after 3 d of BAW feeding. Although parasitism impaired antiherbivore defenses, BAW growth was slower on parasitized tomato leaves. Vines of C. pentagona did not translocate JA from BAW-infested plants: amounts of JA in parasite vines grown on caterpillar-fed and control plants were similar. Parasitized plants generally contained more salicylic acid (SA), which can inhibit JA in some systems. Parasitized mutant (NahG) tomato plants deficient in SA produced more JA in response to insect feeding than parasitized wild-type plants, further suggesting cross talk between the SA and JA defense signaling pathways. However, JA induction by BAW was still reduced in parasitized compared to unparasitized NahG, implying that other factors must be involved. We found that parasitized plants were capable of producing induced volatiles when experimentally treated with JA, indicating that resource depletion by the parasite does not fully explain the observed attenuation of volatile response to herbivore feeding. Collectively, these findings show that parasitic plants can have important consequences for host plant defense against herbivores. PMID:18165323

Butyrate Enhances Disease Resistance of Chickens by Inducing Antimicrobial Host Defense Peptide Gene Expression

PubMed Central

Sunkara, Lakshmi T.; Achanta, Mallika; Schreiber, Nicole B.; Bommineni, Yugendar R.; Dai, Gan; Jiang, Weiyu; Lamont, Susan; Lillehoj, Hyun S.; Beker, Ali; Teeter, Robert G.; Zhang, Guolong

2011-01-01

Host defense peptides (HDPs) constitute a large group of natural broad-spectrum antimicrobials and an important first line of immunity in virtually all forms of life. Specific augmentation of synthesis of endogenous HDPs may represent a promising antibiotic-alternative approach to disease control. In this study, we tested the hypothesis that exogenous administration of butyrate, a major type of short-chain fatty acids derived from bacterial fermentation of undigested dietary fiber, is capable of inducing HDPs and enhancing disease resistance in chickens. We have found that butyrate is a potent inducer of several, but not all, chicken HDPs in HD11 macrophages as well as in primary monocytes, bone marrow cells, and jejuna and cecal explants. In addition, butyrate treatment enhanced the antibacterial activity of chicken monocytes against Salmonella enteritidis, with a minimum impact on inflammatory cytokine production, phagocytosis, and oxidative burst capacities of the cells. Furthermore, feed supplementation with 0.1% butyrate led to a significant increase in HDP gene expression in the intestinal tract of chickens. More importantly, such a feeding strategy resulted in a nearly 10-fold reduction in the bacterial titer in the cecum following experimental infections with S. enteritidis. Collectively, the results indicated that butyrate-induced synthesis of endogenous HDPs is a phylogenetically conserved mechanism of innate host defense shared by mammals and aves, and that dietary supplementation of butyrate has potential for further development as a convenient antibiotic-alternative strategy to enhance host innate immunity and disease resistance. PMID:22073293

Lymphotoxin organizes contributions to host defense and metabolic illness from innate lymphoid cells.

PubMed

Upadhyay, Vaibhav; Fu, Yang-Xin

2014-04-01

The lymphotoxin (LT)-pathway is a unique constituent branch of the Tumor Necrosis Superfamily (TNFSF). Use of LT is a critical mechanism by which fetal innate lymphoid cells regulate lymphoid organogenesis. Within recent years, adult innate lymphoid cells have been discovered to utilize this same pathway to regulate IL-22 and IL-23 production for host defense. Notably, genetic studies have linked polymorphisms in the genes encoding LTα to several phenotypes contributing to metabolic syndrome. The role of the LT-pathway may lay the foundation for a bridge between host immune response, microbiota, and metabolic syndrome. The contribution of the LT-pathway to innate lymphoid cell function and metabolic syndrome will be visited in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways.

PubMed

Yuen, Grace J; Ausubel, Frederick M

2018-12-31

The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.

Both live and dead Enterococci activate Caenorhabditis elegans host defense via immune and stress pathways

PubMed Central

2018-01-01

ABSTRACT The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection. PMID:29436902

Immune defense and host life history.

PubMed

Zuk, Marlene; Stoehr, Andrew M

2002-10-01

Recent interest has focused on immune response in an evolutionary context, with particular attention to disease resistance as a life-history trait, subject to trade-offs against other traits such as reproductive effort. Immune defense has several characteristics that complicate this approach, however; for example, because of the risk of autoimmunity, optimal immune defense is not necessarily maximum immune defense. Two important types of cost associated with immunity in the context of life history are resource costs, those related to the allocation of essential but limited resources, such as energy or nutrients, and option costs, those paid not in the currency of resources but in functional or structural components of the organism. Resource and option costs are likely to apply to different aspects of resistance. Recent investigations into possible trade-offs between reproductive effort, particularly sexual displays, and immunity have suggested interesting functional links between the two. Although all organisms balance the costs of immune defense against the requirements of reproduction, this balance works out differently for males than it does for females, creating sex differences in immune response that in turn are related to ecological factors such as the mating system. We conclude that immune response is indeed costly and that future work would do well to include invertebrates, which have sometimes been neglected in studies of the ecology of immune defense.

Emerging Roles for MAS-Related G Protein-Coupled Receptor-X2 in Host Defense Peptide, Opioid, and Neuropeptide-Mediated Inflammatory Reactions.

PubMed

Ali, Hydar

2017-01-01

Mast cells (MCs) are tissue-resident immune cells that contribute to host defense but are best known for their roles in allergic and inflammatory diseases. In humans, MCs are divided into two subtypes based on the protease content of their secretory granules. Thus, human lung MCs contain only tryptase and are known as MC T , whereas skin MCs contain both tryptase and chymase and are known as MC TC . Patients with severe asthma display elevated MCs in the lung, which undergo phenotypic change from MC T to MC TC . Although the human genome contains four Mas related G protein coupled receptor X (MRGPRX) genes, an important feature of MC TC is that they selectively express MRGPRX2. It is activated by antimicrobial host defense peptides such as human β-defensins and the cathelicidin LL-37 and likely contributes to host defense. MRGPRX2 is also a receptor for the neuropeptide substance P, major basic protein, eosinophil peroxidase, opioids, and many FDA-approved cationic drugs. Increased expression of MRGPRX2 or enhanced downstream signaling likely contributes to chronic inflammatory diseases such as rosacea, atopic dermatitis, chronic urticaria, and severe asthma. In this chapter, I will discuss the expression profile and function of MRGPRX1-4 and review the emerging roles of MRGPRX2 on host defense, chronic inflammatory diseases, and drug-induced pseudoallergic reactions. I will also examine the novel aspects of MRGPRX2 signaling in MCs as it related to degranulation and review the mechanisms of its regulation. © 2017 Elsevier Inc. All rights reserved.

History and update on host defense against vaginal candidiasis.

PubMed

Fidel, Paul L

2007-01-01

Vulvovaginal candidiasis (VVC), caused by Candida albicans, remains a significant problem in women of childbearing age. While cell-mediated immunity is considered the predominant host defense mechanism against mucosal candidal infections, two decades of research from animal models and clinical studies have revealed a lack of a protective role for adaptive immunity against VVC caused by putative immunoregulatory mechanisms. Moreover, natural protective mechanisms and factors associated with susceptibility to infection have remained elusive. That is until recently, when through a live challenge model in humans, it was revealed that protection against vaginitis coincides with a non-inflammatory innate presence, whereas symptomatic infection correlates with a neutrophil infiltrate in the vaginal lumen and elevated fungal burden. Thus, instead of VVC being caused by a putative deficient adaptive immune response, it is now being considered that symptomatic vaginitis is caused by an aggressive innate response.

Analysis of Putative Apoplastic Effectors from the Nematode, Globodera rostochiensis, and Identification of an Expansin-Like Protein That Can Induce and Suppress Host Defenses

PubMed Central

Ali, Shawkat; Magne, Maxime; Chen, Shiyan; Côté, Olivier; Stare, Barbara Gerič; Obradovic, Natasa; Jamshaid, Lubna; Wang, Xiaohong; Bélair, Guy; Moffett, Peter

2015-01-01

The potato cyst nematode, Globodera rostochiensis, is an important pest of potato. Like other pathogens, plant parasitic nematodes are presumed to employ effector proteins, secreted into the apoplast as well as the host cytoplasm, to alter plant cellular functions and successfully infect their hosts. We have generated a library of ORFs encoding putative G. rostochiensis putative apoplastic effectors in vectors for expression in planta. These clones were assessed for morphological and developmental effects on plants as well as their ability to induce or suppress plant defenses. Several CLAVATA3/ESR-like proteins induced developmental phenotypes, whereas predicted cell wall-modifying proteins induced necrosis and chlorosis, consistent with roles in cell fate alteration and tissue invasion, respectively. When directed to the apoplast with a signal peptide, two effectors, an ubiquitin extension protein (GrUBCEP12) and an expansin-like protein (GrEXPB2), suppressed defense responses including NB-LRR signaling induced in the cytoplasm. GrEXPB2 also elicited defense response in species- and sequence-specific manner. Our results are consistent with the scenario whereby potato cyst nematodes secrete effectors that modulate host cell fate and metabolism as well as modifying host cell walls. Furthermore, we show a novel role for an apoplastic expansin-like protein in suppressing intra-cellular defense responses. PMID:25606855

Analysis of putative apoplastic effectors from the nematode, Globodera rostochiensis, and identification of an expansin-like protein that can induce and suppress host defenses.

PubMed

Ali, Shawkat; Magne, Maxime; Chen, Shiyan; Côté, Olivier; Stare, Barbara Gerič; Obradovic, Natasa; Jamshaid, Lubna; Wang, Xiaohong; Bélair, Guy; Moffett, Peter

2015-01-01

The potato cyst nematode, Globodera rostochiensis, is an important pest of potato. Like other pathogens, plant parasitic nematodes are presumed to employ effector proteins, secreted into the apoplast as well as the host cytoplasm, to alter plant cellular functions and successfully infect their hosts. We have generated a library of ORFs encoding putative G. rostochiensis putative apoplastic effectors in vectors for expression in planta. These clones were assessed for morphological and developmental effects on plants as well as their ability to induce or suppress plant defenses. Several CLAVATA3/ESR-like proteins induced developmental phenotypes, whereas predicted cell wall-modifying proteins induced necrosis and chlorosis, consistent with roles in cell fate alteration and tissue invasion, respectively. When directed to the apoplast with a signal peptide, two effectors, an ubiquitin extension protein (GrUBCEP12) and an expansin-like protein (GrEXPB2), suppressed defense responses including NB-LRR signaling induced in the cytoplasm. GrEXPB2 also elicited defense response in species- and sequence-specific manner. Our results are consistent with the scenario whereby potato cyst nematodes secrete effectors that modulate host cell fate and metabolism as well as modifying host cell walls. Furthermore, we show a novel role for an apoplastic expansin-like protein in suppressing intra-cellular defense responses.

A host defense role for a natural antiviral substance in the nervous system.

PubMed

Baron, S; Chopra, A K; Coppenhaver, D H; Gelman, B B; Poast, J; Singh, I P

1998-05-15

The pathogenesis of virus infections of the nervous system (NS) is regulated by host defenses. The defensive role of a major constitutive antiviral substance was studied by determining its distribution in the human nervous system, its concentration and the ability of this viral inhibitor to protect mice against viral infection. The 4000 kDa inhibitor complex in the human nervous system was detected in brain gray and white matter, spinal cord, and sciatic nerve but not in human cerebrospinal fluid. The inhibitor was found in the extracellular medium incubated with minced murine brain. The inhibitory titer ranged from approximately 50 to 200 antiviral units per gram against polio 1, Semliki Forest, Banzi, mengo, Newcastle disease and herpes simplex 1 viruses. The inhibitor is composed of lipid and essential protein and carbohydrate moieties as determined by enzymatic inactivation. Protection of inhibitor-treated mice was demonstrated against both an alphavirus and a picornavirus. Thus a natural defensive role for the broadly antiviral inhibitor is suggested by its constitutively high concentration, wide distribution in nervous system tissues, presence in extracellular fluid and its ability to provide protection in infected mice.

Adenosine A2B Receptor Deficiency Promotes Host Defenses against Gram-Negative Bacterial Pneumonia

PubMed Central

Barletta, Kathryn E.; Cagnina, R. Elaine; Burdick, Marie D.; Linden, Joel

2012-01-01

Rationale: Activation of the adenosine A2B receptor (A2BR) promotes antiinflammatory effects in diverse biological settings, but the role of this receptor in antimicrobial host defense in the lung has not been established. Gram-negative bacillary pneumonia is a common and serious illness associated with high morbidity and mortality, the treatment of which is complicated by increasing rates of antibiotic resistance. Objectives: To test the hypothesis that absence of adenosine A2B receptor signaling promotes host defense against bacterial pneumonia. Methods: We used a model of Klebsiella pneumoniae pneumonia in wild-type mice and mice with targeted deletion of the A2BR. Host responses were compared in vivo and leukocyte responses to the bacteria were examined in vitro. Measurements and Main Results: A2BR–/– mice demonstrated enhanced bacterial clearance from the lung and improved survival after infection with K. pneumoniae compared with wild-type controls, an effect that was mediated by bone marrow–derived cells. Leukocyte recruitment to the lungs and expression of inflammatory cytokines did not differ between A2BR–/– and wild-type mice, but A2BR–/– neutrophils exhibited sixfold greater bactericidal activity and enhanced production of neutrophil extracellular traps compared with wild-type neutrophils when incubated with K. pneumoniae. Consistent with this finding, bronchoalveolar lavage fluid from A2BR–/– mice with Klebsiella pneumonia contained more extracellular DNA compared with wild-type mice with pneumonia. Conclusions: These data suggest that the absence of A2BR signaling enhances antimicrobial activity in gram-negative bacterial pneumonia. PMID:22997203

Ginkgo biloba Responds to Herbivory by Activating Early Signaling and Direct Defenses

PubMed Central

Atsbaha Zebelo, Simon; Foti, Maria; Fliegmann, Judith; Bossi, Simone; Maffei, Massimo E.; Bertea, Cinzia M.

2012-01-01

Background Ginkgo biloba (Ginkgoaceae) is one of the most ancient living seed plants and is regarded as a living fossil. G. biloba has a broad spectrum of resistance or tolerance to many pathogens and herbivores because of the presence of toxic leaf compounds. Little is known about early and late events occurring in G. biloba upon herbivory. The aim of this study was to assess whether herbivory by the generalist Spodoptera littoralis was able to induce early signaling and direct defense in G. biloba by evaluating early and late responses. Methodology/Principal Findings Early and late responses in mechanically wounded leaves and in leaves damaged by S. littoralis included plasma transmembrane potential (Vm) variations, time-course changes in both cytosolic calcium concentration ([Ca2+]cyt) and H2O2 production, the regulation of genes correlated to terpenoid and flavonoid biosynthesis, the induction of direct defense compounds, and the release of volatile organic compounds (VOCs). The results show that G. biloba responded to hebivory with a significant Vm depolarization which was associated to significant increases in both [Ca2+]cyt and H2O2. Several defense genes were regulated by herbivory, including those coding for ROS scavenging enzymes and the synthesis of terpenoids and flavonoids. Metabolomic analyses revealed the herbivore-induced production of several flavonoids and VOCs. Surprisingly, no significant induction by herbivory was found for two of the most characteristic G. biloba classes of bioactive compounds; ginkgolides and bilobalides. Conclusions/Significance By studying early and late responses of G. biloba to herbivory, we provided the first evidence that this “living fossil” plant responds to herbivory with the same defense mechanisms adopted by the most recent angiosperms. PMID:22448229

The history of the early years of metamaterials in USA and UK defense agencies

NASA Astrophysics Data System (ADS)

Derov, John S.; Hammond, Richard; Youngs, Ian J.

2017-08-01

This article discusses the historical events that occurred in the early years of metamaterials leading to the current development of metamaterials in the Defense Advanced Research Projects Agency, Department of Defense, and Ministry of Defence.

IL-32 is a molecular marker of a host defense network in human tuberculosis

PubMed Central

Montoya, Dennis; Inkeles, Megan S.; Liu, Phillip T.; Realegeno, Susan; Teles, Rosane M. B.; Vaidya, Poorva; Munoz, Marcos A.; Schenk, Mirjam; Swindell, William R.; Chun, Rene; Zavala, Kathryn; Hewison, Martin; Adams, John S.; Horvath, Steve; Pellegrini, Matteo; Bloom, Barry R.; Modlin, Robert L.

2014-01-01

Tuberculosis is a leading cause of infectious disease–related death worldwide; however, only 10% of people infected with Mycobacterium tuberculosis develop disease. Factors that contribute to protection could prove to be promising targets for M. tuberculosis therapies. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify potential human candidate markers of host defense by studying gene expression profiles of macrophages, cells that, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene coexpression network analysis revealed an association between the cytokine interleukin-32 (IL-32) and the vitamin D antimicrobial pathway in a network of interferon-γ– and IL-15–induced “defense response” genes. IL-32 induced the vitamin D–dependent antimicrobial peptides cathelicidin and DEFB4 and to generate antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. In addition, the IL-15–induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent compared with active tuberculosis or healthy controls and a coexpression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15–induced gene network. As maintaining M. tuberculosis in a latent state and preventing transition to active disease may represent a form of host resistance, these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis. PMID:25143364

IL-32 is a molecular marker of a host defense network in human tuberculosis.

PubMed

Montoya, Dennis; Inkeles, Megan S; Liu, Phillip T; Realegeno, Susan; Teles, Rosane M B; Vaidya, Poorva; Munoz, Marcos A; Schenk, Mirjam; Swindell, William R; Chun, Rene; Zavala, Kathryn; Hewison, Martin; Adams, John S; Horvath, Steve; Pellegrini, Matteo; Bloom, Barry R; Modlin, Robert L

2014-08-20

Tuberculosis is a leading cause of infectious disease-related death worldwide; however, only 10% of people infected with Mycobacterium tuberculosis develop disease. Factors that contribute to protection could prove to be promising targets for M. tuberculosis therapies. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify potential human candidate markers of host defense by studying gene expression profiles of macrophages, cells that, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene coexpression network analysis revealed an association between the cytokine interleukin-32 (IL-32) and the vitamin D antimicrobial pathway in a network of interferon-γ- and IL-15-induced "defense response" genes. IL-32 induced the vitamin D-dependent antimicrobial peptides cathelicidin and DEFB4 and to generate antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. In addition, the IL-15-induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent compared with active tuberculosis or healthy controls and a coexpression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15-induced gene network. As maintaining M. tuberculosis in a latent state and preventing transition to active disease may represent a form of host resistance, these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis. Copyright © 2014, American Association for the Advancement of Science.

Peptidomic analysis of the extensive array of host-defense peptides in skin secretions of the dodecaploid frog Xenopus ruwenzoriensis (Pipidae).

PubMed

Coquet, Laurent; Kolodziejek, Jolanta; Jouenne, Thierry; Nowotny, Norbert; King, Jay D; Conlon, J Michael

2016-09-01

The Uganda clawed frog Xenopus ruwenzoriensis with a karyotype of 2n=108 is one of the very few vertebrates with dodecaploid status. Peptidomic analysis of norepinephrine-stimulated skin secretions from this species led to the isolation and structural characterization of 23 host-defense peptides belonging to the following families: magainin (3 peptides), peptide glycine-leucine-amide (PGLa; 6 peptides), xenopsin precursor fragment (XPF; 3 peptides), caerulein precursor fragment (CPF; 8 peptides), and caerulein precursor fragment-related peptide (CPF-RP; 3 peptides). In addition, the secretions contained caerulein, identical to the peptide from Xenopus laevis, and two peptides that were identified as members of the trefoil factor family (TFF). The data indicate that silencing of the host-defense peptide genes following polyploidization has been appreciable and non-uniform. Consistent with data derived from comparison of nucleotide sequences of mitochrondrial and nuclear genes, cladistic analyses based upon the primary structures of the host-defense peptides provide support for an evolutionary scenario in which X. ruwenzoriensis arose from an allopolyploidization event involving an octoploid ancestor of the present-day frogs belonging to the Xenopus amieti species group and a tetraploid ancestor of Xenopus pygmaeus. Copyright © 2016 Elsevier Inc. All rights reserved.

Eotaxin-3 (CCL26) exerts innate host defense activities that are modulated by mast cell proteases.

PubMed

Gela, A; Kasetty, G; Jovic, S; Ekoff, M; Nilsson, G; Mörgelin, M; Kjellström, S; Pease, J E; Schmidtchen, A; Egesten, A

2015-02-01

During bacterial infections of the airways, a Th1-profiled inflammation promotes the production of several host defense proteins and peptides with antibacterial activities including β-defensins, ELR-negative CXC chemokines, and the cathelicidin LL-37. These are downregulated by Th2 cytokines of the allergic response. Instead, the eosinophil-recruiting chemokines eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26 are expressed. This study set out to investigate whether these chemokines could serve as innate host defense molecules during allergic inflammation. Antibacterial activities of the eotaxins were investigated using viable count assays, electron microscopy, and methods assessing bacterial permeabilization. Fragments generated by mast cell proteases were characterized, and their potential antibacterial, receptor-activating, and lipopolysaccharide-neutralizing activities were investigated. CCL11, CCL24, and CCL26 all showed potent bactericidal activity, mediated through membrane disruption, against the airway pathogens Streptococcus pneumoniae, Staphylococcus aureus, Nontypeable Haemophilus influenzae, and Pseudomonas aeruginosa. CCL26 retained bactericidal activity in the presence of salt at physiologic concentrations, and the region holding the highest bactericidal activity was the cationic and amphipathic COOH-terminus. Proteolysis of CCL26 by chymase and tryptase, respectively, released distinct fragments of the COOH- and NH2 -terminal regions. The COOH-terminal fragment retained antibacterial activity while the NH2 -terminal had potent LPS-neutralizing properties in the order of CCL26 full-length protein. An identical fragment to NH2 -terminal fragment generated by tryptase was obtained after incubation with supernatants from activated mast cells. None of the fragments activated the CCR3-receptor. Taken together, the findings show that the eotaxins can contribute to host defense against common airway pathogens and that their activities are modulated by

Prophage-mediated defense against viral attack and viral counter-defense

PubMed Central

Dedrick, Rebekah M.; Jacobs-Sera, Deborah; Guerrero Bustamante, Carlos A.; Garlena, Rebecca A.; Mavrich, Travis N.; Pope, Welkin H.; Reyes, Juan C Cervantes; Russell, Daniel A.; Adair, Tamarah; Alvey, Richard; Bonilla, J. Alfred; Bricker, Jerald S.; Brown, Bryony R.; Byrnes, Deanna; Cresawn, Steven G.; Davis, William B.; Dickson, Leon A.; Edgington, Nicholas P.; Findley, Ann M.; Golebiewska, Urszula; Grose, Julianne H.; Hayes, Cory F.; Hughes, Lee E.; Hutchison, Keith W.; Isern, Sharon; Johnson, Allison A.; Kenna, Margaret A.; Klyczek, Karen K.; Mageeney, Catherine M.; Michael, Scott F.; Molloy, Sally D.; Montgomery, Matthew T.; Neitzel, James; Page, Shallee T.; Pizzorno, Marie C.; Poxleitner, Marianne K.; Rinehart, Claire A.; Robinson, Courtney J.; Rubin, Michael R.; Teyim, Joseph N.; Vazquez, Edwin; Ware, Vassie C.; Washington, Jacqueline; Hatfull, Graham F.

2017-01-01

Temperate phages are common and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses infecting mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity, and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages reveals at least five distinct prophage-expressed viral defense systems that interfere with infection of lytic and temperate phages that are either closely-related (homotypic defense) or unrelated (heterotypic defense). Target specificity is unpredictable, ranging from a single target phage to one-third of those tested. The defense systems include a single-subunit restriction system, a heterotypic exclusion system, and a predicted (p)ppGpp synthetase, which blocks lytic phage growth, promotes bacterial survival, and enables efficient lysogeny. The predicted (p)ppGpp synthetase coded by the Phrann prophage defends against phage Tweety infection, but Tweety codes for a tetrapeptide repeat protein, gp54, that acts as a highly effective counter-defense system. Prophage-mediated viral defense offers an efficient mechanism for bacterial success in host-virus dynamics, and counter-defense promotes phage co-evolution. PMID:28067906

The Department of Defense: pioneers of early teledermatology.

PubMed

Rosenbaum, Brooke E; Campion, Campion H; Cohen, Jeffrey M; Latkowski, Jo-Ann

2017-02-15

The United States (US) Department of Defense(DoD) has been a leader in using telecommunicationstechnology to provide remote medical care. The DoDhas been using telemedicine for more than twentyyears to provide medical services to military personneldeployed throughout the world, and has largelyinfluenced the development of teledermatology. Theexperiences of early military teledermatology serviceshave yielded valuable lessons that have been essentialto the creation of successful civilian programs.

NOD2, an Intracellular Innate Immune Sensor Involved in Host Defense and Crohn's Disease

PubMed Central

Strober, Warren; Watanabe, Tomohiro

2013-01-01

Nucleotide binding oligomerization domain 2 (NOD2) is an intracellular sensor for small peptides derived from the bacterial cell wall component, peptidoglycan. Recent studies have uncovered unexpected functions of NOD2 in innate immune responses such as induction of type I IFN and facilitation of autophagy; moreover, they have disclosed extensive cross-talk between NOD2 and Toll-like receptors which plays an indispensable role both in host defense against microbial infection and in the development of autoimmunity. Of particular interest, polymorphisms of CARD15 encoding NOD2 are associated with Crohn's disease and other autoimmune states such as graft versus host disease. In this review, we summarize recent findings regarding normal functions of NOD2 and discuss the mechanisms by which NOD2 polymorphisms associated with Crohn's disease lead to intestinal inflammation. PMID:21750585

Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases.

PubMed

Subramanian, Hariharan; Gupta, Kshitij; Ali, Hydar

2016-09-01

Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, contribute to vascular homeostasis, innate/adaptive immunity, and wound healing. However, MCs are best known for their roles in allergic and inflammatory diseases, such as anaphylaxis, food allergy, rhinitis, itch, urticaria, atopic dermatitis, and asthma. In addition to the high-affinity IgE receptor (FcεRI), MCs express numerous G protein-coupled receptors (GPCRs), which are the largest group of membrane receptor proteins and the most common targets of drug therapy. Antimicrobial host defense peptides, neuropeptides, major basic protein, eosinophil peroxidase, and many US Food and Drug Administration-approved peptidergic drugs activate human MCs through a novel GPCR known as Mas-related G protein-coupled receptor X2 (MRGPRX2; formerly known as MrgX2). Unique features of MRGPRX2 that distinguish it from other GPCRs include their presence both on the plasma membrane and intracellular sites and their selective expression in MCs. In this article we review the possible roles of MRGPRX2 on host defense, drug-induced anaphylactoid reactions, neurogenic inflammation, pain, itch, and chronic inflammatory diseases, such as urticaria and asthma. We propose that host defense peptides that kill microbes directly and activate MCs through MRGPRX2 could serve as novel GPCR targets to modulate host defense against microbial infection. Furthermore, mAbs or small-molecule inhibitors of MRGPRX2 could be developed for the treatment of MC-dependent allergic and inflammatory disorders. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Self/nonself perception in plants in innate immunity and defense

PubMed Central

Sanabria, Natasha M; Huang, Ju-Chi

2010-01-01

The ability to distinguish ‘self’ from ‘nonself’ is the most fundamental aspect of any immune system. The evolutionary solution in plants to the problems of perceiving and responding to pathogens involves surveillance of nonself, damaged-self and altered-self as danger signals. This is reflected in basal resistance or non-host resistance, which is the innate immune response that protects plants against the majority of pathogens. In the case of surveillance of nonself, plants utilize receptor-like proteins or -kinases (RLP/Ks) as pattern recognition receptors (PRRs), which can detect conserved pathogen/microbe-associated molecular pattern (P/MAMP) molecules. P/MAMP detection serves as an early warning system for the presence of a wide range of potential pathogens and the timely activation of plant defense mechanisms. However, adapted microbes express a suite of effector proteins that often interfere or act as suppressors of these defenses. In response, plants have evolved a second line of defense that includes intracellular nucleotide binding leucine-rich repeat (NB-LRR)-containing resistance proteins, which recognize isolate-specific pathogen effectors once the cell wall has been compromised. This host-immunity acts within the species level and is controlled by polymorphic host genes, where resistance protein-mediated activation of defense is based on an ‘altered-self’ recognition mechanism. PMID:21559176

Vertebrate defense against parasites: Interactions between avoidance, resistance, and tolerance.

PubMed

Klemme, Ines; Karvonen, Anssi

2017-01-01

Hosts can utilize different types of defense against the effects of parasitism, including avoidance, resistance, and tolerance. Typically, there is tremendous heterogeneity among hosts in these defense mechanisms that may be rooted in the costs associated with defense and lead to trade-offs with other life-history traits. Trade-offs may also exist between the defense mechanisms, but the relationships between avoidance, resistance, and tolerance have rarely been studied. Here, we assessed these three defense traits under common garden conditions in a natural host-parasite system, the trematode eye-fluke Diplostomum pseudospathaceum and its second intermediate fish host. We looked at host individuals originating from four genetically distinct populations of two closely related salmonid species (Atlantic salmon, Salmo salar and sea trout, Salmo trutta trutta ) to estimate the magnitude of variation in these defense traits and the relationships among them. We show species-specific variation in resistance and tolerance and population-specific variation in resistance. Further, we demonstrate evidence for a trade-off between resistance and tolerance. Our results suggest that the variation in host defense can at least partly result from a compromise between different interacting defense traits, the relative importance of which is likely to be shaped by environmental components. Overall, this study emphasizes the importance of considering different components of the host defense system when making predictions on the outcome of host-parasite interactions.

Roles of Macrophages and Neutrophils in the Early Host Response to Bacillus anthracis Spores in a Mouse Model of Infection

PubMed Central

Cote, Christopher K.; Van Rooijen, Nico; Welkos, Susan L.

2006-01-01

The development of new approaches to combat anthrax requires that the pathogenesis and host response to Bacillus anthracis spores be better understood. We investigated the roles that macrophages and neutrophils play in the progression of infection by B. anthracis in a mouse model. Mice were treated with a macrophage depletion agent (liposome-encapsulated clodronate) or with a neutrophil depletion agent (cyclophosphamide or the rat anti-mouse granulocyte monoclonal antibody RB6-8C5), and the animals were then infected intraperitoneally or by aerosol challenge with fully virulent, ungerminated B. anthracis strain Ames spores. The macrophage-depleted mice were significantly more susceptible to the ensuing infection than the saline-pretreated mice, whereas the differences observed between the neutropenic mice and the saline-pretreated controls were generally not significant. We also found that augmenting peritoneal neutrophil populations before spore challenge did not increase resistance of the mice to infection. In addition, the bacterial load in macrophage-depleted mice was significantly greater and appeared significantly sooner than that observed with the saline-pretreated mice. However, the bacterial load in the neutropenic mice was comparable to that of the saline-pretreated mice. These data suggest that, in our model, neutrophils play a relatively minor role in the early host response to spores, whereas macrophages play a more dominant role in early host defenses against infection by B. anthracis spores. PMID:16369003

Air Pollution and Epigenetics: Effects on SP-A and Innate Host Defense in the Lung

PubMed Central

Silveyra, Patricia; Floros, Joanna

2013-01-01

Summary An appropriate immune and inflammatory response is key to defend against harmful agents present in the environment such as pathogens, allergens, and inhaled pollutants, including ozone and particulate matter. Air pollution is a serious public health concern worldwide, and cumulative evidence revealed that air pollutants contribute to epigenetic variation in several genes, and this in turn can contribute to disease susceptibility. Several groups of experts have recently reviewed findings on epigenetics and air pollution [1–6]. Surfactant proteins play a central role in pulmonary host defense by mediating pathogen clearance, modulating allergic responses and facilitating the resolution of lung inflammation. Recent evidence indicates that surfactant proteins are subject to epigenetic regulation under hypoxia and other conditions. Oxidative stress caused by ozone, and exposure to particulate matter have been shown to affect the expression of surfactant protein A (SP-A), an important lung host defense molecule, as well as alter its functions. In this review, we discuss recent findings in the fields of epigenetics and air pollution effects on innate immunity, with focus on SP-A, and the human SP-A variants in particular. Their function may be differentially affected by pollutants and specifically by ozone-induced oxidative stress, and this in turn may differentially affect susceptibility to lung disease. PMID:22553125

Lawrence Livermore National Laboratory Workshop Characterization of Pathogenicity, Virulence and Host-Pathogen Interactions

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

Krishnan, A

2006-08-30

The threats of bio-terrorism and newly emerging infectious diseases pose serious challenges to the national security infrastructure. Rapid detection and diagnosis of infectious disease in human populations, as well as characterizing pathogen biology, are critical for reducing the morbidity and mortality associated with such threats. One of the key challenges in managing an infectious disease outbreak, whether through natural causes or acts of overt terrorism, is detection early enough to initiate effective countermeasures. Much recent attention has been directed towards the utility of biomarkers or molecular signatures that result from the interaction of the pathogen with the host for improvingmore » our ability to diagnose and mitigate the impact of a developing infection during the time window when effective countermeasures can be instituted. Host responses may provide early signals in blood even from localized infections. Multiple innate and adaptive immune molecules, in combination with other biochemical markers, may provide disease-specific information and new targets for countermeasures. The presence of pathogen specific markers and an understanding of the molecular capabilities and adaptations of the pathogen when it interacts with its host may likewise assist in early detection and provide opportunities for targeting countermeasures. An important question that needs to be addressed is whether these molecular-based approaches will prove useful for early diagnosis, complement current methods of direct agent detection, and aid development and use of countermeasures. Lawrence Livermore National Laboratory (LLNL) will host a workshop to explore the utility of host- and pathogen-based molecular diagnostics, prioritize key research issues, and determine the critical steps needed to transition host-pathogen research to tools that can be applied towards a more effective national bio-defense strategy. The workshop will bring together leading researchers

Geminivirus-encoded TrAP suppressor inhibits the histone methyltransferase SUVH4/KYP to counter host defense

PubMed Central

Castillo-González, Claudia; Liu, Xiuying; Huang, Changjun; Zhao, Changjiang; Ma, Zeyang; Hu, Tao; Sun, Feng; Zhou, Yijun; Zhou, Xueping; Wang, Xiu-Jie; Zhang, Xiuren

2015-01-01

Transcriptional gene silencing (TGS) can serve as an innate immunity against invading DNA viruses throughout Eukaryotes. Geminivirus code for TrAP protein to suppress the TGS pathway. Here, we identified an Arabidopsis H3K9me2 histone methyltransferase, Su(var)3-9 homolog 4/Kryptonite (SUVH4/KYP), as a bona fide cellular target of TrAP. TrAP interacts with the catalytic domain of KYP and inhibits its activity in vitro. TrAP elicits developmental anomalies phenocopying several TGS mutants, reduces the repressive H3K9me2 mark and CHH DNA methylation, and reactivates numerous endogenous KYP-repressed loci in vivo. Moreover, KYP binds to the viral chromatin and controls its methylation to combat virus infection. Notably, kyp mutants support systemic infection of TrAP-deficient Geminivirus. We conclude that TrAP attenuates the TGS of the viral chromatin by inhibiting KYP activity to evade host surveillance. These findings provide new insight on the molecular arms race between host antiviral defense and virus counter defense at an epigenetic level. DOI: http://dx.doi.org/10.7554/eLife.06671.001 PMID:26344546

Serum Lipoproteins Are Critical for Pulmonary Innate Defense against Staphylococcus aureus Quorum Sensing.

PubMed

Manifold-Wheeler, Brett C; Elmore, Bradley O; Triplett, Kathleen D; Castleman, Moriah J; Otto, Michael; Hall, Pamela R

2016-01-01

Hyperlipidemia has been extensively studied in the context of atherosclerosis, whereas the potential health consequences of the opposite extreme, hypolipidemia, remain largely uninvestigated. Circulating lipoproteins are essential carriers of insoluble lipid molecules and are increasingly recognized as innate immune effectors. Importantly, severe hypolipidemia, which may occur with trauma or critical illness, is clinically associated with bacterial pneumonia. To test the hypothesis that circulating lipoproteins are essential for optimal host innate defense in the lung, we used lipoprotein-deficient mice and a mouse model of Staphylococcus aureus pneumonia in which invasive infection requires virulence factor expression controlled by the accessory gene regulator (agr) operon. Activation of agr and subsequent virulence factor expression is inhibited by apolipoprotein B, the structural protein of low-density lipoprotein, which binds and sequesters the secreted agr-signaling peptide (AIP). In this article, we report that lipoprotein deficiency impairs early pulmonary innate defense against S. aureus quorum-sensing-dependent pathogenesis. Specifically, apolipoprotein B levels in the lung early postinfection are significantly reduced with lipoprotein deficiency, coinciding with impaired host control of S. aureus agr-signaling and increased agr-dependent morbidity (weight loss) and inflammation. Given that lipoproteins also inhibit LTA- and LPS-mediated inflammation, these results suggest that hypolipidemia may broadly impact posttrauma pneumonia susceptibility to both Gram-positive and -negative pathogens. Together with previous reports demonstrating that hyperlipidemia also impairs lung innate defense, these results suggest that maintenance of normal serum lipoprotein levels is necessary for optimal host innate defense in the lung. Copyright © 2015 by The American Association of Immunologists, Inc.

A Diverse Family of Host-Defense Peptides (Piscidins) Exhibit Specialized Anti-Bacterial and Anti-Protozoal Activities in Fishes.

PubMed

Salger, Scott A; Cassady, Katherine R; Reading, Benjamin J; Noga, Edward J

2016-01-01

Conventional antibiotics and other chemical-based drugs are currently one of the most common methods used to control disease-related mortality in animal agriculture. Use of the innate immune system to decrease disease related mortalities is a novel alternative to conventional drugs. One component of the innate immune system is the host-defense peptides, also known as antimicrobial peptides. Host-defense peptides are typically small, amphipathic, α-helical peptides with a broad-spectrum of action against viral, bacterial, fungal, and/or protozoal pathogens. Piscidins are host-defense peptides first discovered in the hybrid striped bass (white bass, Morone chrysops, x striped bass, M. saxatilis). In this paper we identify four new piscidin isoforms in the hybrid striped bass and describe their tissue distributions. We also determine the progenitor species of origin of each piscidin (orthology) and propose a revised nomenclature for this newly described piscidin family based on a three class system. The Class I piscidins (22 amino acids in length; striped bass and white bass piscidin 1 and piscidin 3) show broad-spectrum activity against bacteria and ciliated protozoans, while the Class III piscidins (55 amino acids in length; striped bass and white bass piscidin 6 and striped bass piscidin 7) primarily show anti-protozoal activity. The Class II piscidins (44-46 amino acids in length; striped bass and white bass piscidin 4 and white bass piscidin 5) have a level of activity against bacteria and protozoans intermediate to Classes I and III. Knowledge of piscidin function and activity may help in the future development of disease-resistant lines of striped bass and white bass that could be used to produce superior hybrids for aquaculture.

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

Role of early experience in ant enslavement: a comparative analysis of a host and a non-host species

PubMed Central

Blatrix, Rumsaïs; Sermage, Claire

2005-01-01

Background Ants use the odour of the colony to discriminate nestmates. In some species, this odour is learned during the first days following emergence, and thus early experience has a strong influence on nestmate discrimination. Slave-making ants are social parasites that capture brood of other ant species to increase the worker force of their colony. After emerging in the slave-maker nest, slave workers work as if they were in their own colony. We tested the hypothesis that early experience allows the deception of commonly enslaved species, while non-host species use a different mechanism, which does not involve learning. Results Pupae of a host species, Temnothorax unifasciatus, and a non-host species, T. parvulus, were allowed to emerge in the presence of workers of one of two slave-maker species, Chalepoxenus muellerianus or Myrmoxenus ravouxi. When T. unifasciatus was exposed to slave-makers for 10 days following emergence, they were more aggressive towards their own sisters and groomed the slave-maker more. T. parvulus gave a less clear result: while workers behaved more aggressively towards their sisters when exposed early to C. muellerianus workers, this was not the case when exposed early to M. ravouxi workers. Moreover, T. parvulus workers allogroomed conspecific nestmates less than T. unifasciatus. Allogrooming activity might be very important for the slave-makers because they are tended by their slaves. Conclusion Our findings show that early experience influences nestmate discrimination in the ant T. unifasciatus and can account for the successful enslavement of this species. However, the non-host species T. parvulus is less influenced by the early environment. This might help to explain why this species is never used by social parasites. PMID:16076389

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.

A porin-like protein from oral secretions of Spodoptera littoralis larvae induces defense-related early events in plant leaves.

PubMed

Guo, Huijuan; Wielsch, Natalie; Hafke, Jens B; Svatoš, Aleš; Mithöfer, Axel; Boland, Wilhelm

2013-09-01

Insect herbivory on plants is a complex incident consisting of at least two different aspects, namely mechanical damage and chemical challenge, as feeding insects introduce oral secretions (OS) into the wounded tissue of the attacked plant. Mechanical wounding alone is sufficient to induce a set of defense-related reactions in host plants, but some early events such as membrane potential (Vm) changes and cytosolic Ca²⁺-elevations can be triggered only by herbivores suggesting that OS-derived molecules are involved in those processes. Following an assay-guided purification based on planar lipid bilayer membrane technique in combination with proteomic analysis, a porin-like protein (PLP) of most likely bacterial origin was determined from collected OS of Spodoptera littoralis larvae. PLP exhibited channel-forming activity. Further, early defense-related events in plant-insect interaction were evaluated by using a purified fraction and α-hemolysin (α-HL) as a commercial pore-forming compound. Both up-regulated the calmodulin-like CML42 in Arabidopsis thaliana, which only responds to oral secretion and not to wounding. An elevation of in vivo [Ca²⁺](cyt) was not observed. Because membrane channel formation is a widespread phenomenon in plant-insect interactions, this PLP might represent an example for microbial compounds from the insect gut which are initially involved in plant-insect interactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

M-CSF Mediates Host Defense during Bacterial Pneumonia by Promoting the Survival of Lung and Liver Mononuclear Phagocytes.

PubMed

Bettina, Alexandra; Zhang, Zhimin; Michels, Kathryn; Cagnina, R Elaine; Vincent, Isaah S; Burdick, Marie D; Kadl, Alexandra; Mehrad, Borna

2016-06-15

Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells, and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. M-CSF has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden, and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, proliferation of precursors, or recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and antimicrobial functions of both lung and liver mononuclear phagocytes during pneumonia, and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M-CSF is critical to host defenses against bacterial pneumonia by mediating survival and antimicrobial functions of mononuclear phagocytes in the lungs and liver. Copyright © 2016 by The American Association of Immunologists, Inc.

M-CSF mediates host defense during bacterial pneumonia by promoting the survival of lung and liver mononuclear phagocytes

PubMed Central

Bettina, Alexandra; Zhang, Zhimin; Michels, Kathryn; Cagnina, R. Elaine; Vincent, Isaah S.; Burdick, Marie D.; Kadl, Alexandra; Mehrad, Borna

2016-01-01

Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. Macrophage-colony stimulating factor (M-CSF) has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, the proliferation of precursors or the recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and anti-microbial functions of both lung and liver mononuclear phagocytes during pneumonia and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M-CSF is critical to host defenses against bacterial pneumonia by mediating survival and anti-microbial functions of mononuclear phagocytes in the lungs and liver. PMID:27183631

Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus aureus Promotes Host Defense with Minimal Impact on Resistance

PubMed Central

Sully, Erin K.; Malachowa, Natalia; Elmore, Bradley O.; Alexander, Susan M.; Femling, Jon K.; Gray, Brian M.; DeLeo, Frank R.; Otto, Michael; Cheung, Ambrose L.; Edwards, Bruce S.; Sklar, Larry A.; Horswill, Alexander R.; Hall, Pamela R.; Gresham, Hattie D.

2014-01-01

Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus. S. aureus is the primary cause of acute bacterial skin and soft tissue infections (SSTIs) and the quorum sensing operon agr is causally associated with these. Whether efficacious chemical inhibitors of agr signaling can be developed that promote host defense against SSTIs while sparing the normal microbiota of the skin is unknown. In a high throughput screen, we identified a small molecule inhibitor (SMI), savirin (S. aureus virulence inhibitor) that disrupted agr-mediated quorum sensing in this pathogen but not in the important skin commensal Staphylococcus epidermidis. Mechanistic studies employing electrophoretic mobility shift assays and a novel AgrA activation reporter strain revealed the transcriptional regulator AgrA as the target of inhibition within the pathogen, preventing virulence gene upregulation. Consistent with its minimal impact on exponential phase growth, including skin microbiota members, savirin did not provoke stress responses or membrane dysfunction induced by conventional antibiotics as determined by transcriptional profiling and membrane potential and integrity studies. Importantly, savirin was efficacious in two murine skin infection models, abating tissue injury and selectively promoting clearance of agr+ but not Δagr bacteria when administered at the time of infection or delayed until maximal abscess development. The mechanism of enhanced host defense involved in part enhanced intracellular killing of agr+ but not Δagr in macrophages and by low pH. Notably, resistance or tolerance to savirin inhibition of agr was not observed after multiple passages either in vivo or in vitro where under the same conditions resistance to growth inhibition was induced after passage with conventional antibiotics. Therefore, chemical inhibitors can selectively target AgrA in

A novel pathogenicity gene is required in the rice blast fungus to suppress the basal defenses of the host.

PubMed

Chi, Myoung-Hwan; Park, Sook-Young; Kim, Soonok; Lee, Yong-Hwan

2009-04-01

For successful colonization and further reproduction in host plants, pathogens need to overcome the innate defenses of the plant. We demonstrate that a novel pathogenicity gene, DES1, in Magnaporthe oryzae regulates counter-defenses against host basal resistance. The DES1 gene was identified by screening for pathogenicity-defective mutants in a T-DNA insertional mutant library. Bioinformatic analysis revealed that this gene encodes a serine-rich protein that has unknown biochemical properties, and its homologs are strictly conserved in filamentous Ascomycetes. Targeted gene deletion of DES1 had no apparent effect on developmental morphogenesis, including vegetative growth, conidial germination, appressorium formation, and appressorium-mediated penetration. Conidial size of the mutant became smaller than that of the wild type, but the mutant displayed no defects on cell wall integrity. The Deltades1 mutant was hypersensitive to exogenous oxidative stress and the activity and transcription level of extracellular enzymes including peroxidases and laccases were severely decreased in the mutant. In addition, ferrous ion leakage was observed in the Deltades1 mutant. In the interaction with a susceptible rice cultivar, rice cells inoculated with the Deltades1 mutant exhibited strong defense responses accompanied by brown granules in primary infected cells, the accumulation of reactive oxygen species (ROS), the generation of autofluorescent materials, and PR gene induction in neighboring tissues. The Deltades1 mutant displayed a significant reduction in infectious hyphal extension, which caused a decrease in pathogenicity. Notably, the suppression of ROS generation by treatment with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases, resulted in a significant reduction in the defense responses in plant tissues challenged with the Deltades1 mutant. Furthermore, the Deltades1 mutant recovered its normal infectious growth in DPI-treated plant tissues. These results

Unraveling the Armor of a Killer: Evasion of Host Defenses by African Swine Fever Virus.

PubMed

Reis, Ana Luisa; Netherton, Chris; Dixon, Linda K

2017-03-15

African swine fever is an acute hemorrhagic disease of pigs. Extensive recent spread in the Russian Federation and Eastern Europe has increased the risk to global pig production. The virus is a large DNA virus and is the only member of the Asfarviridae family. In pigs, the virus replicates predominantly in macrophages. We review how the virus overcomes the barriers to replication in the macrophage and the virus mechanism to inhibit key host defense pathways. Copyright © 2017 American Society for Microbiology.

Host defense peptides of thrombin modulate inflammation and coagulation in endotoxin-mediated shock and Pseudomonas aeruginosa sepsis.

PubMed

Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; Mörgelin, Matthias; van der Plas, Mariena J A; Rydengård, Victoria; Malmsten, Martin; Albiger, Barbara; Schmidtchen, Artur

2012-01-01

Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin in vitro and in vivo. Furthermore, they interfere with coagulation by modulating contact activation and tissue factor-mediated clotting in vitro, leading to normalization of coagulation responses in vivo, a previously unknown function of host defense peptides. In a mouse model of Pseudomonas aeruginosa sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate bacterial levels, pro-inflammatory responses, and coagulation, renders them attractive therapeutic candidates for the treatment of invasive infections and sepsis.

Relative Roles of the Cellular and Humoral Responses in the Drosophila Host Defense against Three Gram-Positive Bacterial Infections

PubMed Central

Cho, Ju Hyun; Lee, Janice; Lafarge, Marie-Céline; Kocks, Christine; Ferrandon, Dominique

2011-01-01

Background Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense. Methodology/Principal Findings In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different Gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus), we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival – independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response. Conclusions/Significance Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen. PMID:21390224

Human host defense peptides - role in maintaining human homeostasis and pathological processes.

PubMed

Dawgul, Malgorzata Anna; Greber, Katarzyna Ewa; Sawicki, Wieslaw; Kamysz, Wojciech

2016-12-12

The human body expresses over 100 host defense peptides and proteins (antimicrobial peptides, AMPs). The compounds are produced by tissues and mucosal surfaces, e.g. skin, the digestive and urinary tract, the ocular surface and neutrophils, and are believed to play a crucial role in defense from microbial infection. They are considered to protect the human body against microbial infections due to their antimicrobial and immunomodulatory activities. As well as having strong antimicrobial activity towards a broad spectrum of microorganisms, AMPs have been found to interact with neutrophils, monocytes and T-cells and promote the production of cytokines. They also neutralize the action of lipopolysaccharide (LPS) and play a crucial role in wound healing processes. In response to the microbial stimuli the AMPs are released in order to fight the infection, however there are several microorganisms evading the human immune system by downregulation of AMPs. Decreased or elevated expression of AMPs is associated also with several non-infectious diseases. Despite numerous studies conducted in the field of AMPs over the last few decades, their exact role in physiological and pathological processes remains to be explained. In this paper, we review the most significant human AMPs and their potential roles in maintaining human homeostasis as well as in pathological processes.

Herpesvirus tegument and immediate early proteins are pioneers in the battle between viral infection and nuclear domain 10-related host defense.

PubMed

Zhang, Kuan; van Drunen Littel-van den Hurk, Sylvia

2017-06-15

The sophisticated anti-viral functions of nuclear domain 10 (ND10) are revealed by identifying the role of each component and the countermeasures applied by viruses. Several ND10 proteins suppress herpesviruses at initial and early phases of infection. Herpesviruses need to antagonize these anti-viral proteins to start a productive infection. In this review the recently identified similarities and differences among the strategies adopted by the three subfamilies of herpesviruses are discussed, highlighting that one of the significant purposes of incorporating tegument proteins into the viral particles might be to counteract ND10 proteins immediately after the viral genome enters the host nucleus. Once the infection progresses, a sufficient amount of immediate early proteins is expressed to disperse and hydrolyze ND10 proteins, accelerating the development of infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of zinc-finger anti-viral protein in host defense against Sindbis virus

PubMed Central

Kozaki, Tatsuya; Takahama, Michihiro; Misawa, Takuma; Matsuura, Yoshiharu; Saitoh, Tatsuya

2015-01-01

Accumulating evidence indicates that type I interferon (IFN) mediates the host protective response to RNA viruses. However, the anti-viral effector molecules involved in this response have not been fully identified. Here, we show that zinc-finger anti-viral protein (ZAP), an IFN-inducible gene, plays a critical role in the elimination of Sindbis virus (SINV) in vitro and in vivo. The loss of ZAP greatly enhances the replication of SINV but does not inhibit type I IFN production in primary mouse embryonic fibroblasts (MEFs). ZAP binds and destabilizes SINV RNA, thereby suppressing the replication of SINV. Type I IFN fails to suppress SINV replication in ZAP-deficient MEFs, whereas the ectopic expression of ZAP is sufficient to suppress the replication of SINV in MEFs lacking the expression of type I IFN and the IFN-inducible genes. ZAP-deficient mice are highly susceptible to SINV infection, although they produce sufficient amounts of type I IFN. Therefore, ZAP is an RNA-sensing anti-viral effector molecule that mediates the type-I-IFN-dependent host defense against SINV. PMID:25758257

ALD1 Regulates Basal Immune Components and Early Inducible Defense Responses in Arabidopsis.

PubMed

Cecchini, Nicolás M; Jung, Ho Won; Engle, Nancy L; Tschaplinski, Timothy J; Greenberg, Jean T

2015-04-01

Robust immunity requires basal defense machinery to mediate timely responses and feedback cycles to amplify defenses against potentially spreading infections. AGD2-LIKE DEFENSE RESPONSE PROTEIN 1 (ALD1) is needed for the accumulation of the plant defense signal salicylic acid (SA) during the first hours after infection with the pathogen Pseudomonas syringae and is also upregulated by infection and SA. ALD1 is an aminotransferase with multiple substrates and products in vitro. Pipecolic acid (Pip) is an ALD1-dependent bioactive product induced by P. syringae. Here, we addressed roles of ALD1 in mediating defense amplification as well as the levels and responses of basal defense machinery. ALD1 needs immune components PAD4 and ICS1 (an SA synthesis enzyme) to confer disease resistance, possibly through a transcriptional amplification loop between them. Furthermore, ALD1 affects basal defense by controlling microbial-associated molecular pattern (MAMP) receptor levels and responsiveness. Vascular exudates from uninfected ALD1-overexpressing plants confer local immunity to the wild type and ald1 mutants yet are not enriched for Pip. We infer that, in addition to affecting Pip accumulation, ALD1 produces non-Pip metabolites that play roles in immunity. Thus, distinct metabolite signals controlled by the same enzyme affect basal and early defenses versus later defense responses, respectively.

Proteomic approaches to understanding the role of the cytoskeleton in host-defense mechanisms

PubMed Central

Radulovic, Marko; Godovac-Zimmermann, Jasminka

2014-01-01

The cytoskeleton is a cellular scaffolding system whose functions include maintenance of cellular shape, enabling cellular migration, division, intracellular transport, signaling and membrane organization. In addition, in immune cells, the cytoskeleton is essential for phagocytosis. Following the advances in proteomics technology over the past two decades, cytoskeleton proteome analysis in resting and activated immune cells has emerged as a possible powerful approach to expand our understanding of cytoskeletal composition and function. However, so far there have only been a handful of studies of the cytoskeleton proteome in immune cells. This article considers promising proteomics strategies that could augment our understanding of the role of the cytoskeleton in host-defense mechanisms. PMID:21329431

Salmonella Utilizes Zinc To Subvert Antimicrobial Host Defense of Macrophages via Modulation of NF-κB Signaling

PubMed Central

Wu, Aimin; Haschka, David; Heeke, Simon; Dichtl, Stefanie; Petzer, Verena; Seifert, Markus; Hilbe, Richard; Sopper, Sieghart; Talasz, Heribert; Bumann, Dirk; Lass-Flörl, Cornelia; Theurl, Igor; Zhang, Keying

2017-01-01

ABSTRACT Zinc sequestration by macrophages is considered a crucial host defense strategy against infection by the intracellular bacterium Salmonella enterica serovar Typhimurium. However, the underlying mechanisms remain elusive. In this study, we found that zinc favors pathogen survival within macrophages. Salmonella-hosting macrophages contained higher free zinc levels than did uninfected macrophages and cells that successfully eliminated bacteria, which was paralleled by the impaired production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in bacterium-harboring cells. A profound, zinc-mediated inhibition of NF-κB p65 transcriptional activity affecting the expression of the ROS- and RNS-forming enzymes phos47 and inducible nitric oxide synthase (iNOS) provided a mechanistic explanation for this phenomenon. Macrophages responded to infection by enhancing the expression of zinc-scavenging metallothioneins 1 and 2, whose genetic deletion caused increased free zinc levels, reduced ROS and RNS production, and increased the survival of Salmonella. Our data suggest that Salmonella invasion of macrophages results in a bacterium-driven increase in the intracellular zinc level, which weakens antimicrobial defense and the ability of macrophages to eradicate the pathogen. Thus, limitation of cytoplasmic zinc levels may help to control infection by intracellular bacteria. PMID:28874447

Host-defense peptides from skin secretions of the octoploid frogs Xenopus vestitus and Xenopus wittei (Pipidae): insights into evolutionary relationships.

PubMed

Mechkarska, Milena; Coquet, Laurent; Leprince, Jérôme; Jouenne, Thierry; Vaudry, Hubert; Michalak, Katarzyna; Michalak, Pawel; Conlon, J Michael

2014-09-01

The primary structures of host-defense peptides have proved useful in elucidating the evolution history of frogs. Peptidomic analysis was used to compare the diversity of host-defense peptides in norepinephrine-stimulated skin secretions from the octoploid frogs, Xenopus vestitus (Kivu clawed frog) and Xenopus wittei (De Witte's clawed frog) in the family Pipidae. Structural characterization demonstrated that the X. vestitus peptides belong to the magainin (3 peptides), peptide glycine-leucine-amide (PGLa; 4 peptides), xenopsin-precursor fragment (XPF; 1 peptide), and caerulein-precursor fragment (CPF; 5 peptides) families. The X. wittei peptides comprise magainin (4 peptides), PGLa (1 peptide), XPF (2 peptides), and CPF (7 peptides). In addition, secretions from both species contain caerulein, identical to the peptide from Xenopus laevis, but X. wittei secretions contains the novel peptide [R4K]xenopsin. The variability in the numbers of paralogs in each peptide family indicates a selective silencing of the host-defense peptide genes following the polyploidization events. The primary structures of the peptides provide insight into phylogenetic relationships among the octoploid Xenopus frogs. The data support a sister-group relationship between X. vestitus and Xenopus lenduensis, suggestive of bifurcating speciation after allopolyploidization, whereas X. wittei is more closely related to the Xenopus amieti-Xenopus andrei group suggesting a common tetraploid ancestor. Consistent with previous data, the CPF peptides showed the highest growth inhibitory activity against bacteria with CPF-W6 (GIGSLLAKAAKLAAGLV.NH2) combining high antimicrobial potency against Staphylococcus aureus (MIC=4 μM) with relatively low hemolytic activity (LC50=190 μM). Copyright © 2014 Elsevier Inc. All rights reserved.

Salmonella utilizes zinc to subvert anti-microbial host defense of macrophages via modulation of NF-κB signaling.

PubMed

Wu, Aimin; Tymoszuk, Piotr; Haschka, David; Heeke, Simon; Dichtl, Stefanie; Petzer, Verena; Seifert, Markus; Hilbe, Richard; Sopper, Sieghart; Talasz, Heribert; Bumann, Dirk; Lass-Flörl, Cornelia; Theurl, Igor; Zhang, Keying; Weiss, Guenter

2017-09-05

Zinc sequestration by macrophages is considered a crucial host defense strategy against infection with the intracellular bacterium Salmonella Typhimurium. However, the underlying mechanisms remain elusive. In this study we found zinc to favor pathogen survival within macrophages. Salmonella -hosting macrophages contained higher free zinc levels than uninfected macrophages and cells that successfully eliminated bacteria, which was paralleled by impaired production of reactive oxygen (ROS) and nitrogen (RNS) species in bacteria-harboring cells. A profound, zinc-mediated inhibition of NF-κB p65 transcriptional activity affecting expression of the ROS- and RNS-forming enzymes phos47 and iNOS provided a mechanistic explanation for this phenomenon. Macrophages responded to infection by enhanced expression of zinc scavenging methallothioneins-1 and 2, whose genetic deletion caused a rise of free zinc levels, reduced ROS and RNS production and increased survival of Salmonella Our data suggest that Salmonella invasion of macrophages results in a bacteria-driven rise of intracellular zinc levels which weakens anti-microbial defense and the ability of macrophages to eradicate the pathogen. Thus, limitation of cytoplasmic zinc levels may help to control infection with intracellular bacteria. Copyright © 2017 Wu et al.

Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides

PubMed Central

Li, Hao; Anuwongcharoen, Nuttapat; Malik, Aijaz Ahmad; Prachayasittikul, Virapong; Wikberg, Jarl E. S.; Nantasenamat, Chanin

2016-01-01

Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of d-amino acids (d-AA) is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of d-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists. Given the impact that d-AA incorporation has on HDPs, this review aims to fill that void with a systematic discussion of the impact of d-AA on HDPs. PMID:27376281

Budesonide suppresses pulmonary antibacterial host defense by down-regulating cathelicidin-related antimicrobial peptide in allergic inflammation mice and in lung epithelial cells

PubMed Central

2013-01-01

Background Glucocorticoids are widely regarded as the most effective treatment for asthma. However, the direct impact of glucocorticoids on the innate immune system and antibacterial host defense during asthma remain unclear. Understanding the mechanisms underlying this process is critical to the clinical application of glucocorticoids for asthma therapy. After sensitization and challenge with ovalbumin (OVA), BALB/c mice were treated with inhaled budesonide and infected with Pseudomonas aeruginosa (P. aeruginosa). The number of viable bacteria in enflamed lungs was evaluated, and levels of interleukin-4 (IL-4) and interferon-γ (IFN-γ) in serum were measured. A lung epithelial cell line was pretreated with budesonide. Levels of cathelicidin-related antimicrobial peptide (CRAMP) were measured by immunohistochemistry and western blot analysis. Intracellular bacteria were observed in lung epithelial cells. Results Inhaled budesonide enhanced lung infection in allergic mice exposed to P. aeruginosa and increased the number of viable bacteria in lung tissue. Higher levels of IL-4 and lower levels of IFN-γ were observed in the serum. Budesonide decreased the expression of CRAMP, increased the number of internalized P. aeruginosa in OVA-challenged mice and in lung epithelial cell lines. These data indicate that inhaled budesonide can suppress pulmonary antibacterial host defense by down-regulating CRAMP in allergic inflammation mice and in cells in vitro. Conclusions Inhaled budesonide suppressed pulmonary antibacterial host defense in an asthmatic mouse model and in lung epithelium cells in vitro. This effect was dependent on the down-regulation of CRAMP. PMID:23387852

Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

PubMed Central

2011-01-01

Background Human exposure to nanoparticles (NPs) and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu) NPs using a model of lung inflammation and host defense. Methods We used Klebsiella pneumoniae (K.p.) in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3) and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse). Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH) activity, and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Results Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse). Conclusions Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection. PMID:21943386

Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock.

PubMed

Yamada, Noriaki; Martin, Lukas B; Zechendorf, Elisabeth; Purvis, Gareth S D; Chiazza, Fausto; Varrone, Barbara; Collino, Massimo; Shepherd, Joanna; Heinbockel, Lena; Gutsmann, Thomas; Correa, Wilmar; Brandenburg, Klaus; Marx, Gernot; Schuerholz, Tobias; Brohi, Karim; Thiemermann, Christoph

2017-03-10

To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27-32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser, and (3) phosphorylation of IκBα on Ser resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.

The host defense peptide beta-defensin 1 confers protection against Bordetella pertussis in newborn piglets.

PubMed

Elahi, Shokrollah; Buchanan, Rachelle M; Attah-Poku, Sam; Townsend, Hugh G G; Babiuk, Lorne A; Gerdts, Volker

2006-04-01

Innate immunity plays an important role in protection against respiratory infections in humans and animals. Host defense peptides such as beta-defensins represent major components of innate immunity. We recently developed a novel porcine model of pertussis, an important respiratory disease of young children and infants worldwide. Here, we investigated the role of porcine beta-defensin 1 (pBD-1), a porcine defensin homologue of human beta-defensin 2, in conferring protection against respiratory infection with Bordetella pertussis. In this model, newborn piglets were fully susceptible to infection and developed severe bronchopneumonia. In contrast, piglets older than 4 weeks of age were protected against infection with B. pertussis. Protection was associated with the expression of pBD-1 in the upper respiratory tract. In fact, pBD-1 expression was developmentally regulated, and the absence of pBD-1 was thought to contribute to the increased susceptibility of newborn piglets to infection with B. pertussis. Bronchoalveolar lavage specimens collected from older animals as well as chemically synthesized pBD-1 displayed strong antimicrobial activity against B. pertussis in vitro. Furthermore, in vivo treatment of newborn piglets with only 500 mug pBD-1 at the time of challenge conferred protection against infection with B. pertussis. Interestingly, pBD-1 displayed no bactericidal activity in vitro against Bordetella bronchiseptica, a closely related natural pathogen of pigs. Our results demonstrate that host defense peptides play an important role in protection against pertussis and are essential in modulating innate immune responses against respiratory infections.

The 11S Proteasome Subunit PSME3 Is a Positive Feedforward Regulator of NF-κB and Important for Host Defense against Bacterial Pathogens.

PubMed

Sun, Jinxia; Luan, Yi; Xiang, Dong; Tan, Xiao; Chen, Hui; Deng, Qi; Zhang, Jiaojiao; Chen, Minghui; Huang, Hongjun; Wang, Weichao; Niu, Tingting; Li, Wenjie; Peng, Hu; Li, Shuangxi; Li, Lei; Tang, Wenwen; Li, Xiaotao; Wu, Dianqing; Wang, Ping

2016-02-02

The NF-κB pathway plays important roles in immune responses. Although its regulation has been extensively studied, here, we report an unknown feedforward mechanism for the regulation of this pathway by Toll-like receptor (TLR) ligands in macrophages. During bacterial infections, TLR ligands upregulate the expression of the 11S proteasome subunit PSME3 via NF-κB-mediated transcription in macrophages. PSME3, in turn, enhances the transcriptional activity of NF-κB by directly binding to and destabilizing KLF2, a negative regulator of NF-κB transcriptional activity. Consistent with this positive role of PSME3 in NF-κB regulation and importance of the NF-κB pathway in host defense against bacterial infections, the lack of PSME3 in hematopoietic cells renders the hosts more susceptible to bacterial infections, accompanied by increased bacterial burdens in host tissues. Thus, this study identifies a substrate for PSME3 and elucidates a proteolysis-dependent, but ubiquitin-independent, mechanism for NF-κB regulation that is important for host defense and innate immunity. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Pregnane X Receptor Regulates Pathogen-Induced Inflammation and Host Defense against an Intracellular Bacterial Infection through Toll-like Receptor 4.

PubMed

Qiu, Zhijuan; Cervantes, Jorge L; Cicek, Basak B; Mukherjee, Subhajit; Venkatesh, Madhukumar; Maher, Leigh A; Salazar, Juan C; Mani, Sridhar; Khanna, Kamal M

2016-08-23

The nuclear pregnane X receptor (PXR) plays a central role in regulating xenobiotic metabolism. We now report a novel role for PXR as a critical negative regulator of innate immunity after infection. Pxr(-/-) mice exhibited remarkably elevated pro-inflammatory cytokine and chemokine production following infection with Listeria monocytogenes (Lm). Despite the more robust innate immune response, Pxr(-/-) mice were highly susceptible to Lm infection. Surprisingly, disruption of the Toll-like receptor 4 (TLR4) but not TLR2 signaling restored the inflammation to normal levels and the ability to clear Lm in Pxr(-/-) mice. Mechanistically, the heightened inflammation in Pxr(-/-) mice resulted in the death of inflammatory monocytes that led to the enhanced susceptibility to Lm infection. These data demonstrated that PXR regulated pathogen-induced inflammation and host defense against Lm infection through modulating the TLR4 pathway. In summary, we discovered an apical role for PXR in regulating innate immunity. In addition, we uncovered a remarkable negative impact of the TLR4 pathway in controlling the quality of the inflammatory response and host defense against a gram-positive bacterial infection.

Rac2 Functions in Both Neutrophils and Macrophages To Mediate Motility and Host Defense in Larval Zebrafish.

PubMed

Rosowski, Emily E; Deng, Qing; Keller, Nancy P; Huttenlocher, Anna

2016-12-15

Leukocyte motility is required for host defense responses. Rac-family Rho GTPases are implicated in leukocyte function; however, the distinct roles of different Rac isoforms in host defense in vivo have remained unclear. In this study, we generated Rac2-deficient zebrafish using transcription activator-like effector nucleases to directly compare the role of Rac2 in vivo in neutrophils and macrophages in motility and the response to infection. This zebrafish larval model is highly amenable to live imaging of leukocyte behavior, and we report that in rac2 -/- larvae both neutrophils and macrophages are defective in basic motility, leading to impaired responses to localized wounds or infections. rac2 -/- larvae are highly susceptible to infection with Pseudomonas aeruginosa, which can be almost fully rescued by ectopic expression of either Rac2 or Rac1 specifically in neutrophils, indicating that these isoforms have partially overlapping functions in vivo. Rescue of Rac2 expression specifically in macrophages also confers resistance to Pseudomonas infection, highlighting an important role for Rac2 in this leukocyte population as well. Surprisingly, in contrast to neutrophils expressing a Rac2 dominant inhibitory human disease mutation, rac2 -/- neutrophils do not have altered polarity or mobilization from hematopoietic tissue, suggesting that a different Rac isoform, such as Rac1, also contributes to these phenotypes in vivo. Copyright © 2016 by The American Association of Immunologists, Inc.

Aggregatibacter actinomycetemcomitans, a potent immunoregulator of the periodontal host defense system and alveolar bone homeostasis

PubMed Central

Herbert, Bethany A.; Novince, Chad M.; Kirkwood, Keith L.

2015-01-01

Summary Aggregatibacter actinomycetemcomitans is a perio-pathogenic bacteria that has long been associated with localized aggressive periodontitis. The mechanisms of its pathogenicity have been studied in humans and pre-clinical experimental models. Although different serotypes of A. actinomycetemcomitans have differential virulence factor expression, A. actinomycetemcomitans cytolethal distending toxin (CDT), leukotoxin, and lipopolysaccharide (LPS) have been most extensively studied in the context of modulating the host immune response. Following colonization and attachment in the oral cavity, A. actinomycetemcomitans employs CDT, leukotoxin, and LPS to evade host innate defense mechanisms and drive a pathophysiologic inflammatory response. This supra-physiologic immune response state perturbs normal periodontal tissue remodeling/turnover and ultimately has catabolic effects on periodontal tissue homeostasis. In this review, we have divided the host response into two systems: non-hematopoietic and hematopoietic. Non-hematopoietic barriers include epithelium and fibroblasts that initiate the innate immune host response. The hematopoietic system contains lymphoid and myeloid-derived cell lineages that are responsible for expanding the immune response and driving the pathophysiologic inflammatory state in the local periodontal microenvironment. Effector systems and signaling transduction pathways activated and utilized in response to A. actinomycetemcomitans will be discussed to further delineate immune cell mechanisms during A. actinomycetemcomitans infection. Finally, we will discuss the osteo-immunomodulatory effects induced by A. actinomycetemcomitans and dissect the catabolic disruption of balanced osteoclast-osteoblast mediated bone remodeling, which subsequently leads to net alveolar bone loss. PMID:26197893

Hepatocyte-mediated cytotoxicity and host defense mechanisms in the alcohol-injured liver.

PubMed

McVicker, Benita L; Thiele, Geoffrey M; Tuma, Dean J; Casey, Carol A

2014-09-01

The consumption of alcohol is associated with many health issues including alcoholic liver disease (ALD). The natural history of ALD involves the development of steatosis, inflammation (steatohepatitis), fibrosis and cirrhosis. During the stage of steatohepatitis, the combination of inflammation and cellular damage can progress to a severe condition termed alcoholic hepatitis (AH). Unfortunately, the pathogenesis of AH remains uncharacterized. Some modulations have been identified in host defense and liver immunity mechanisms during AH that highlight the role of intrahepatic lymphocyte accumulation and associated inflammatory cytokine responses. Also, it is hypothesized that alcohol-induced injury to liver cells may significantly contribute to the aberrant lymphocytic distribution that is seen in AH. In particular, the regulation of lymphocytes by hepatocytes may be disrupted in the alcoholic liver resulting in altered immunologic homeostasis and perpetuation of disease. In recent studies, it was demonstrated that the direct killing of activated T lymphocytes by hepatocytes is facilitated by the asialoglycoprotein receptor (ASGPR). The ASGPR is a well-characterized glycoprotein receptor that is exclusively expressed by hepatocytes. This hepatic receptor is known for its role in the clearance of desialylated glycoproteins or cells, yet neither its physiological function nor its role in disease states has been determined. Interestingly, alcohol markedly impairs ASGPR function; however, the effect alcohol has on ASGPR-mediated cytotoxicity of lymphocytes remains to be elucidated. This review discusses the contribution of hepatocytes in immunological regulation and, importantly, how pathological effects of ethanol disrupt hepatocellular-mediated defense mechanisms.

Formylpeptide receptors are critical for rapid neutrophil mobilization in host defense against Listeria monocytogenes

PubMed Central

Liu, Mingyong; Chen, Keqiang; Yoshimura, Teizo; Liu, Ying; Gong, Wanghua; Wang, Aimin; Gao, Ji-Liang; Murphy, Philip M.; Wang, Ji Ming

2012-01-01

Listeria monocytogenes (Listeria) causes opportunistic infection in immunocompromised hosts with high mortality. Resistance to Listeria depends on immune responses and recruitment of neutrophils of the immune system into infected sites is an early and critical step. Mouse neutrophils express two G protein-coupled formylpeptide receptor subtypes Fpr1 and Fpr2 that recognize bacterial and host-derived chemotactic molecules including Listeria peptides for cell migration and activation. Here we report deficiency in Fprs exacerbated the severity of the infection and increased the mortality of infected mice. The mechanism involved impaired early neutrophil recruitment to the liver with Fpr1 and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant signals and for production of bactericidal superoxide. Thus, Fprs are essential sentinels to guide the first wave of neutrophil infiltration in the liver of Listeria-infected mice for effective elimination of the invading pathogen. PMID:23139859

Indirect Plant Defense against Insect Herbivores: A Review

USDA-ARS?s Scientific Manuscript database

Plants respond to herbivore attack by launching two types of defenses: direct defense and indirect defense. Direct defense includes all plant traits that increase the resistance of host plants to attacking insect herbivores by affecting the physiology and/or behavior of the attackers. Indirect defe...

Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication

PubMed Central

König, Renate; Zhou, Yingyao; Elleder, Daniel; Diamond, Tracy L.; Bonamy, Ghislain M.C.; Irelan, Jeffrey T.; Chiang, Chih-yuan; Tu, Buu P.; De Jesus, Paul D.; Lilley, Caroline E.; Seidel, Shannon; Opaluch, Amanda M.; Caldwell, Jeremy S.; Weitzman, Matthew D.; Kuhen, Kelli L.; Bandyopadhyay, Sourav; Ideker, Trey; Orth, Anthony P.; Miraglia, Loren J.; Bushman, Frederic D.; Young, John A.; Chanda, Sumit K.

2008-01-01

Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection. PMID:18854154

Channel formation by serum amyloid A: a potential mechanism for amyloid pathogenesis and host defense.

PubMed

Hirakura, Yutaka; Carreras, Isabel; Sipe, Jean D; Kagan, Bruce L

2002-03-01

Serum amyloid A (SAA) is a family of closely related apolipoproteins associated with high density lipoprotein (HDL). Subclasses of SAA isoforms are differentially expressed constitutively and during inflammation. During states of infection or inflammation, levels of HDL bound, acute phase isoforms of SAA rise as much as 1000-fold in the serum, suggesting that it might play a role in host defense. Following recurrent or chronic inflammation, an N-terminal peptide fragment of SAA known as amyloid A (AA) assembles into fibrils causing extensive damage to spleen, liver, and kidney, and rapidly progressing to death. In the present paper, we report the novel finding that a recombinant acute phase isoform variant of human SAA 1.1 (SAAp) readily forms ion-channels in planar lipid bilayer membranes at physiologic concentrations. These channels are voltage-independent, poorly selective, and are relatively long-lived This type of channel would place a severe metabolic strain on various kinds of cells. Expression of human SAA 1.1 in bacteria induces lysis of bacterial cells, while expression of the constitutive isoform (human SAA4) does not. Secondary structural analysis of the SAA isoforms in dicates a strong hydrophobicity of the N-terminal of the acute phase isoform relative to the constitutive SAA4 isoform, which may be responsible for the bactericidal activity of the former, in keeping with the notion that SAA 1 targets cell membranes and forms channels in them. Channel formation may thus be related to a host defense role of acute phase SAA isoforms and may also be the mechanism of end organ damage in AA and other amyloidoses.

A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

PubMed

Devchand, Pallavi R; Schmidt, Birgitta A; Primo, Valeria C; Zhang, Qing-yin; Arnaout, M Amin; Serhan, Charles N; Nikolic, Boris

2005-02-01

Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) are potent endogenous lipid mediators thought to define the inflammatory set-point. We used single prophylactic administrations of a synthetic aspirin-triggered lipoxin A(4) signal mimetic, ATLa, to probe dynamics of early host-donor interactions in a mouse model for the inflammation-associated multifactorial disease of allogeneic bone marrow transplant (BMT) -induced graft-vs.-host disease (GvHD). We first demonstrated that both host and donor are responsive to the ATLa signals. The simple and restricted regimen of a single prophylactic administration of ATLa [100 ng/mL to donor cells or 1 microg (approximately 50 microg/kg) i.v. to host] was sufficient to delay death. Clinical indicators of weight, skin lesions, diarrhea and eye inflammation were monitored. Histological analyses on day 45 post-BMT showed that the degree of cellular trafficking, particularly neutrophil infiltrate, and protection of end-organ target pathology are different, depending on whether the host or donor was treated with ATLa. Taken together, these results chart some ATLa protective effects on GvHD cellular dynamics over time and identify a previously unrecognized effect of host neutrophils in the early phase post-BMT as important determinants in the dynamics of GvHD onset and progression.-Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q.-y., Arnaout, M. A., Serhan, C. N., Nikolic, B. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

Mobilization of lipids and fortification of cell wall and cuticle are important in host defense against Hessian fly

PubMed Central

2013-01-01

Background Wheat – Hessian fly interaction follows a typical gene-for-gene model. Hessian fly larvae die in wheat plants carrying an effective resistance gene, or thrive in susceptible plants that carry no effective resistance gene. Results Gene sets affected by Hessian fly attack in resistant plants were found to be very different from those in susceptible plants. Differential expression of gene sets was associated with differential accumulation of intermediates in defense pathways. Our results indicated that resources were rapidly mobilized in resistant plants for defense, including extensive membrane remodeling and release of lipids, sugar catabolism, and amino acid transport and degradation. These resources were likely rapidly converted into defense molecules such as oxylipins; toxic proteins including cysteine proteases, inhibitors of digestive enzymes, and lectins; phenolics; and cell wall components. However, toxicity alone does not cause immediate lethality to Hessian fly larvae. Toxic defenses might slow down Hessian fly development and therefore give plants more time for other types of defense to become effective. Conclusion Our gene expression and metabolic profiling results suggested that remodeling and fortification of cell wall and cuticle by increased deposition of phenolics and enhanced cross-linking were likely to be crucial for insect mortality by depriving Hessian fly larvae of nutrients from host cells. The identification of a large number of genes that were differentially expressed at different time points during compatible and incompatible interactions also provided a foundation for further research on the molecular pathways that lead to wheat resistance and susceptibility to Hessian fly infestation. PMID:23800119

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.

Induction of Jasmonic Acid-Associated Defenses by Thrips Alters Host Suitability for Conspecifics and Correlates with Increased Trichome Densities in Tomato

PubMed Central

Klinkhamer, Peter G.L.; Leiss, Kirsten A.

2017-01-01

Plant defenses inducible by herbivorous arthropods can determine performance of subsequent feeding herbivores. We investigated how infestation of tomato (Solanum lycopersicum) plants with the Western flower thrips (Frankliniella occidentalis) alters host plant suitability and foraging decisions of their conspecifics. We explored the role of delayed-induced jasmonic acid (JA)-mediated plant defense responses in thrips preference by using the tomato mutant def-1, impaired in JA biosynthesis. In particular, we investigated the effect of thrips infestation on trichome-associated tomato defenses. The results showed that when offered a choice, thrips preferred non-infested plants over infested wild-type plants, while no differences were observed in def-1. Exogenous application of methyl jasmonate restored the repellency effect in def-1. Gene expression analysis showed induction of the JA defense signaling pathway in wild-type plants, while activating the ethylene signaling pathway in both genotypes. Activation of JA defenses led to increases in type-VI leaf glandular trichome densities in the wild type, augmenting the production of trichome-associated volatiles, i.e. terpenes. Our study revealed that plant-mediated intraspecific interactions between thrips are determined by JA-mediated defenses in tomato. We report that insects can alter not only trichome densities but also the allelochemicals produced therein, and that this response might depend on the magnitude and/or type of the induction. PMID:28158865

Host-Pathogen interactions modulated by small RNAs.

PubMed

Islam, Waqar; Islam, Saif Ul; Qasim, Muhammad; Wang, Liande

2017-07-03

Biological processes such as defense mechanisms and microbial offense strategies are regulated through RNA induced interference in eukaryotes. Genetic mutations are modulated through biogenesis of small RNAs which directly impacts upon host development. Plant defense mechanisms are regulated and supported by a diversified group of small RNAs which are involved in streamlining several RNA interference pathways leading toward the initiation of pathogen gene silencing mechanisms. In the similar context, pathogens also utilize the support of small RNAs to launch their offensive attacks. Also there are strong evidences about the active involvement of these RNAs in symbiotic associations. Interestingly, small RNAs are not limited to the individuals in whom they are produced; they also show cross kingdom influences through variable interactions with other species thus leading toward the inter-organismic gene silencing. The phenomenon is understandable in the microbes which utilize these mechanisms to overcome host defense line. Understanding the mechanism of triggering host defense strategies can be a valuable step toward the generation of disease resistant host plants. We think that the cross kingdom trafficking of small RNA is an interesting insight that is needed to be explored for its vitality.

Host-Pathogen interactions modulated by small RNAs

PubMed Central

Islam, Waqar; Islam, Saif ul; Qasim, Muhammad; Wang, Liande

2017-01-01

ABSTRACT Biological processes such as defense mechanisms and microbial offense strategies are regulated through RNA induced interference in eukaryotes. Genetic mutations are modulated through biogenesis of small RNAs which directly impacts upon host development. Plant defense mechanisms are regulated and supported by a diversified group of small RNAs which are involved in streamlining several RNA interference pathways leading toward the initiation of pathogen gene silencing mechanisms. In the similar context, pathogens also utilize the support of small RNAs to launch their offensive attacks. Also there are strong evidences about the active involvement of these RNAs in symbiotic associations. Interestingly, small RNAs are not limited to the individuals in whom they are produced; they also show cross kingdom influences through variable interactions with other species thus leading toward the inter-organismic gene silencing. The phenomenon is understandable in the microbes which utilize these mechanisms to overcome host defense line. Understanding the mechanism of triggering host defense strategies can be a valuable step toward the generation of disease resistant host plants. We think that the cross kingdom trafficking of small RNA is an interesting insight that is needed to be explored for its vitality. PMID:28430077

Aphid (Myzus persicae) feeding on the parasitic plant dodder (Cuscuta australis) activates defense responses in both the parasite and soybean host.

PubMed

Zhuang, Huifu; Li, Juan; Song, Juan; Hettenhausen, Christian; Schuman, Meredith C; Sun, Guiling; Zhang, Cuiping; Li, Jing; Song, Dunlun; Wu, Jianqiang

2018-06-01

Dodders (Cuscuta spp.) are shoot holoparasites, whose haustoria penetrate host tissues to enable fusion between the parasite and host vascular systems, allowing Cuscuta to extract water, nutrients and other molecules from hosts. Aphids are piercing-sucking herbivores that use specialized stylets to feed on phloem sap. Aphids are known to feed on Cuscuta, but how Cuscuta and its host plant respond to aphids attacking the parasite was unknown. Phytohormone quantification, transcriptomic analysis and bioassays were performed to determine the responses of Cuscuta australis and its soybean (Glycine max) hosts to the feeding of green peach aphid (GPA; Myzus persicae) on C. australis. Decreased salicylic acid levels and 172 differentially expressed genes (DEGs) were found in GPA-attacked C. australis, and the soybean hosts exhibited increased jasmonic acid contents and 1015 DEGs, including > 100 transcription factor genes. Importantly, GPA feeding on C. australis increased the resistance of the soybean host to subsequent feeding by the leafworm Spodoptera litura and soybean aphid Aphis glycines, resulting in 21% decreased leafworm mass and 41% reduced aphid survival rate. These data strongly suggest that GPA feeding on Cuscuta induces a systemic signal, which is translocated to hosts and activates defense against herbivores. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Hypervirulent Diuraphis noxia (Hemiptera: Aphididae) biotype SAM avoids triggering defenses in its host (Triticum aestivum) (Poales: Poaceae) during feeding.

PubMed

Botha, Anna-Maria; Burger, N Francois V; Van Eck, Leon

2014-06-01

In the molecular arms race between aphids and plants, both organisms rely on adaptive strategies to outcompete their evolutionary rival. In the current study, we investigated the difference in elicited defense responses of wheat (Triticum aestivum L.) near-isogenic lines with different Dn resistance genes, upon feeding by an avirulent and hypervirulent Diuraphis noxia Kurdjumov biotype. After measuring the activity of a suite of enzymes associated with plant defense, it became apparent that the host does not recognize the invasion by the hypervirulent aphid because none of these were induced, while feeding by the avirulent biotype did result in induction of enzyme activity. Genomic plasticity in D. noxia may be a likely explanation for the observed differences in virulence between D. noxia biotype SA1 and SAM, as demonstrated in the current study.

An Arabidopsis Lipid Flippase Is Required for Timely Recruitment of Defenses to the Host-Pathogen Interface at the Plant Cell Surface.

PubMed

Underwood, William; Ryan, Andrew; Somerville, Shauna C

2017-06-05

Deposition of cell wall-reinforcing papillae is an integral component of the plant immune response. The Arabidopsis PENETRATION 3 (PEN3) ATP binding cassette (ABC) transporter plays a role in defense against numerous pathogens and is recruited to sites of pathogen detection where it accumulates within papillae. However, the trafficking pathways and regulatory mechanisms contributing to recruitment of PEN3 and other defenses to the host-pathogen interface are poorly understood. Here, we report a confocal microscopy-based screen to identify mutants with altered localization of PEN3-GFP after inoculation with powdery mildew fungi. We identified a mutant, aberrant localization of PEN3 3 (alp3), displaying accumulation of the normally plasma membrane (PM)-localized PEN3-GFP in endomembrane compartments. The mutant was found to be disrupted in the P 4 -ATPase AMINOPHOSPHOLIPID ATPASE 3 (ALA3), a lipid flippase that plays a critical role in vesicle formation. We provide evidence that PEN3 undergoes continuous endocytic cycling from the PM to the trans-Golgi network (TGN). In alp3, PEN3 accumulates in the TGN, causing delays in recruitment to the host-pathogen interface. Our results indicate that PEN3 and other defense proteins continuously cycle through the TGN and that timely exit of these proteins from the TGN is critical for effective pre-invasive immune responses against powdery mildews. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

Interplay of Pathogen-Induced Defense Responses and Symbiotic Establishment in Medicago truncatula

PubMed Central

Chen, Tao; Duan, Liujian; Zhou, Bo; Yu, Haixiang; Zhu, Hui; Cao, Yangrong; Zhang, Zhongming

2017-01-01

Suppression of host innate immunity appears to be required for the establishment of symbiosis between rhizobia and host plants. In this study, we established a system that included a host plant, a bacterial pathogen and a symbiotic rhizobium to study the role of innate immunity during symbiotic interactions. A pathogenic bacterium, Pseudomonas syringae pv. tomato strain DC3000 (Pst DC3000), was shown to cause chlorosis in Medicago truncatula A17. Sinorhizobium meliloti strain Sm2011 (Sm2011) and Pst DC3000 strain alone induced similar defense responses in M. truncatula. However, when co-inoculated, Sm2011 specifically suppressed the defense responses induced by Pst DC3000, such as MAPK activation and ROS production. Inoculation with Sm2011 suppressed the transcription of defense-related genes triggered by Pst DC3000 infection, including the receptor of bacterial flagellin (FLS2), pathogenesis-related protein 10 (PR10), and the transcription factor WRKY33. Interestingly, inoculation with Pst DC3000 specifically inhibited the expression of the symbiosis marker genes nodule inception and nodulation pectate lyase and reduced the numbers of infection threads and nodules on M. truncatula A17 roots, indicating that Pst DC3000 inhibits the establishment of symbiosis in M. truncatula. In addition, defense-related genes, such as MAPK3/6, RbohC, and WRKY33, exhibited a transient increase in their expression in the early stage of symbiosis with Sm2011, but the expression dropped down to normal levels at later symbiotic stages. Our results suggest that plant innate immunity plays an antagonistic role in symbiosis by directly reducing the numbers of infection threads and nodules. PMID:28611764

Western Spruce Budworm Consumption-Effects of Host Species and Foliage Chemistry

Treesearch

Michael R. Wagner; Elizabeth A.  Blake

1983-01-01

Feeding efficiencies and growth rates of western spruce budworm larvae varied among hosts tested. Pupae attained normal size regardless of host species. Candidate defensive compounds (tannins and phenols) varied only slightly with the vigor of the host. The relationship between these defensive compounds and measures of larvae growth were not entirely consistent with...

Dynamic defense workshop :

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

Crosby, Sean Michael; Doak, Justin E.; Haas, Jason Juedes.

2013-02-01

On September 5th and 6th, 2012, the Dynamic Defense Workshop: From Research to Practice brought together researchers from academia, industry, and Sandia with the goals of increasing collaboration between Sandia National Laboratories and external organizations, de ning and un- derstanding dynamic, or moving target, defense concepts and directions, and gaining a greater understanding of the state of the art for dynamic defense. Through the workshop, we broadened and re ned our de nition and understanding, identi ed new approaches to inherent challenges, and de ned principles of dynamic defense. Half of the workshop was devoted to presentations of current state-of-the-artmore » work. Presentation topics included areas such as the failure of current defenses, threats, techniques, goals of dynamic defense, theory, foundations of dynamic defense, future directions and open research questions related to dynamic defense. The remainder of the workshop was discussion, which was broken down into sessions on de ning challenges, applications to host or mobile environments, applications to enterprise network environments, exploring research and operational taxonomies, and determining how to apply scienti c rigor to and investigating the eld of dynamic defense.« less

The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus fumigatus.

PubMed

Dewi, Intan M W; van de Veerdonk, Frank L; Gresnigt, Mark S

2017-10-04

The ubiquitous opportunistic fungal pathogen Aspergillus fumigatus rarely causes infections in immunocompetent individuals. A healthy functional innate immune system plays a crucial role in preventing Aspergillus -infection. This pivotal role for the innate immune system makes it a main research focus in studying the pathogenesis of aspergillosis. Although sometimes overshadowed by the innate immune response, the adaptive immune response, and in particular T-helper responses, also represents a key player in host defense against Aspergillus . Virtually all T-helper subsets have been described to play a role during aspergillosis, with the Th1 response being crucial for fungal clearance. However; morbidity and mortality of aspergillosis can also be partly attributed to detrimental immune responses resulting from adaptive immune activation. Th2 responses benefit fungal persistence; and are the foundation of allergic forms of aspergillosis. The Th17 response has two sides; although crucial for granulocyte recruitment, it can be involved in detrimental immunopathology. Regulatory T-cells, the endogenous regulators of inflammatory responses, play a key role in controlling detrimental inflammatory responses during aspergillosis. The current knowledge of the adaptive immune response against A. fumigatus is summarized in this review. A better understanding on how T-helper responses facilitate clearance of Aspergillus -infection and control inflammation can be the fundamental basis for understanding the pathogenesis of aspergillosis and for the development of novel host-directed therapies.

Neuroinflammatory contributions to pain after SCI: roles for central glial mechanisms and nociceptor-mediated host defense.

PubMed

Walters, Edgar T

2014-08-01

Neuropathic pain after spinal cord injury (SCI) is common, often intractable, and can be severely debilitating. A number of mechanisms have been proposed for this pain, which are discussed briefly, along with methods for revealing SCI pain in animal models, such as the recently applied conditioned place preference test. During the last decade, studies of animal models have shown that both central neuroinflammation and behavioral hypersensitivity (indirect reflex measures of pain) persist chronically after SCI. Interventions that reduce neuroinflammation have been found to ameliorate pain-related behavior, such as treatment with agents that inhibit the activation states of microglia and/or astroglia (including IL-10, minocycline, etanercept, propentofylline, ibudilast, licofelone, SP600125, carbenoxolone). Reversal of pain-related behavior has also been shown with disruption by an inhibitor (CR8) and/or genetic deletion of cell cycle-related proteins, deletion of a truncated receptor (trkB.T1) for brain-derived neurotrophic factor (BDNF), or reduction by antisense knockdown or an inhibitor (AMG9810) of the activity of channels (TRPV1 or Nav1.8) important for electrical activity in primary nociceptors. Nociceptor activity is known to drive central neuroinflammation in peripheral injury models, and nociceptors appear to be an integral component of host defense. Thus, emerging results suggest that spinal and systemic effects of SCI can activate nociceptor-mediated host defense responses that interact via neuroinflammatory signaling with complex central consequences of SCI to drive chronic pain. This broader view of SCI-induced neuroinflammation suggests new targets, and additional complications, for efforts to develop effective treatments for neuropathic SCI pain. Copyright © 2014 Elsevier Inc. All rights reserved.

Leg massage therapy promotes psychological relaxation and reinforces the first-line host defense in cancer patients.

PubMed

Noto, Yuka; Kitajima, Maiko; Kudo, Mihoko; Okudera, Koichi; Hirota, Kazuyoshi

2010-12-01

Patients with cancer suffer a wide range of physical symptoms coupled with psychological stress. Moreover, cancer chemotherapy induces immunosuppression and consequently causes respiratory infections. Massage therapy has been reported to reduce symptoms in cancer patients via an increase in psychosocial relaxation and to enhance and/or improve immune function. In the present study, we determined whether leg massage could induce psychosocial relaxation and activate the first line of the host defense system. To assess effects of rest and leg massage, 15 healthy volunteers rested on a bed for 20 min on the first day, and 3 days later the subjects received a standardized massage of the legs for 20 min with nonaromatic oil. Twenty-nine cancer patients also received the same standardized massage of the legs. Anxiety/stress was assessed before and just after the rest or the massage using the State-Trait Anxiety Inventory (STAI-s) and visual analogue scale (VAS). To evaluate oral immune function, salivary chromogranin A (CgA) and secretory immunoglobulin A (sIgA) levels were measured. In healthy volunteers, rest significantly reduced VAS by 34% and increased sIgA by 61%. In contrast, leg massage significantly reduced both STAI-s and VAS by 24% and 63%, and increased both sIgA and CgA by 104% and 90%, respectively. In cancer patients, leg massage significantly decreased both STAI-s and VAS by 16% and 38%, and increased both salivary CgA and sIgA by 33% and 35%, respectively. Leg massage may promote psychosocial relaxation and reinforce a first-line host defense with an increase in secretion of antimicrobial peptides.

Pas de deux: An Intricate Dance of Anther Smut and Its Host.

PubMed

San Toh, Su; Chen, Zehua; Rouchka, Eric C; Schultz, David J; Cuomo, Christina A; Perlin, Michael H

2018-02-02

The successful interaction between pathogen/parasite and host requires a delicate balance between fitness of the former and survival of the latter. To optimize fitness a parasite/pathogen must effectively create an environment conducive to reproductive success, while simultaneously avoiding or minimizing detrimental host defense response. The association between Microbotryum lychnidis-dioicae and its host Silene latifolia serves as an excellent model to examine such interactions. This fungus is part of a species complex that infects species of the Caryophyllaceae, replacing pollen with the fungal spores. In the current study, transcriptome analyses of the fungus and its host were conducted during discrete stages of bud development so as to identify changes in fungal gene expression that lead to spore development and to identify changes associated with infection in the host plant. In contrast to early biotrophic phase stages of infection for the fungus, the latter stages involve tissue necrosis and in the case of infected female flowers, further changes in the developmental program in which the ovary aborts and a pseudoanther is produced. Transcriptome analysis via Illumina RNA sequencing revealed enrichment of fungal genes encoding small secreted proteins, with hallmarks of effectors and genes found to be relatively unique to the Microbotryum species complex. Host gene expression analyses also identified interesting sets of genes up-regulated, including those involving stress response, host defense response, and several agamous-like MADS-box genes (AGL61 and AGL80), predicted to interact and be involved in male gametophyte development. Copyright © 2018 Toh et al.

Graves' disease: a host defense mechanism gone awry.

PubMed

Kohn, L D; Napolitano, G; Singer, D S; Molteni, M; Scorza, R; Shimojo, N; Kohno, Y; Mozes, E; Nakazato, M; Ulianich, L; Chung, H K; Matoba, H; Saunier, B; Suzuki, K; Schuppert, F; Saji, M

2000-01-01

In this report we summarize evidence to support a model for the development of Graves' disease. The model suggests that Graves' disease is initiated by an insult to the thyrocyte in an individual with a normal immune system. The insult, infectious or otherwise, causes double strand DNA or RNA to enter the cytoplasm of the cell. This causes abnormal expression of major histocompatibility (MHC) class I as a dominant feature, but also aberrant expression of MHC class II, as well as changes in genes or gene products needed for the thyrocyte to become an antigen presenting cell (APC). These include increased expression of proteasome processing proteins (LMP2), transporters of antigen peptides (TAP), invariant chain (Ii), HLA-DM, and the co-stimulatory molecule, B7, as well as STAT and NF-kappaB activation. A critical factor in these changes is the loss of normal negative regulation of MHC class I, class II, and thyrotropin receptor (TSHR) gene expression, which is necessary to maintain self-tolerance during the normal changes in gene expression involved in hormonally-increased growth and function of the cell. Self-tolerance to the TSHR is maintained in normals because there is a population of CD8- cells which normally suppresses a population of CD4+ cells that can interact with the TSHR if thyrocytes become APCs. This is a host self-defense mechanism that we hypothesize leads to autoimmune disease in persons, for example, with a specific viral infection, a genetic predisposition, or even, possibly, a TSHR polymorphism. The model is suggested to be important to explain the development of other autoimmune diseases including systemic lupus or diabetes.

Lassa and Marburg viruses elicit distinct host transcriptional responses early after infection.

PubMed

Caballero, Ignacio S; Yen, Judy Y; Hensley, Lisa E; Honko, Anna N; Goff, Arthur J; Connor, John H

2014-11-06

Lassa virus and Marburg virus are two causative agents of viral hemorrhagic fever. Their diagnosis is difficult because patients infected with either pathogen present similar nonspecific symptoms early after infection. Current diagnostic tests are based on detecting viral proteins or nucleic acids in the blood, but these cannot be found during the early stages of disease, before the virus starts replicating in the blood. Using the transcriptional response of the host during infection can lead to earlier diagnoses compared to those of traditional methods. In this study, we use RNA sequencing to obtain a high-resolution view of the in vivo transcriptional dynamics of peripheral blood mononuclear cells (PBMCs) throughout both types of infection. We report a subset of host mRNAs, including heat-shock proteins like HSPA1B, immunoglobulins like IGJ, and cell adhesion molecules like SIGLEC1, whose differences in expression are strong enough to distinguish Lassa infection from Marburg infection in non-human primates. We have validated these infection-specific expression differences by using microarrays on a larger set of samples, and by quantifying the expression of individual genes using RT-PCR. These results suggest that host transcriptional signatures are correlated with specific viral infections, and that they can be used to identify highly pathogenic viruses during the early stages of disease, before standard detection methods become effective.

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

Isolation, identification, and quantification of potential defensive compounds in the viceroy butterfly and its larval host-plant, Carolina willow.

PubMed

Prudic, Kathleen L; Khera, Smriti; Sólyom, Anikó; Timmermann, Barbara N

2007-06-01

The viceroy-monarch and viceroy-queen butterfly associations are classic examples of mimicry. These relationships were originally classified as Batesian, or parasitic, but were later reclassified as Müllerian, or mutalistic, based on predator bioassays. The Müllerian reclassification implies that viceroy is unpalatable because it too is chemically defended like the queen and the monarch. However, unlike the queen and the monarch, the viceroy defensive chemistry has remained uncharacterized. We demonstrate that the viceroy butterfly (Limenitis archippus, Nymphalidae) not only sequesters nonvolatile defensive compounds from its larval host-plant, the Carolina willow (Salix caroliniana, Salicaceae), but also secretes volatile defensive compounds when disturbed. We developed liquid chromatography-mass spectrometry-mass spectrometry methods to identify a set of phenolic glycosides shared between the adult viceroy butterfly and the Carolina willow, and solid phase microextraction and gas chromatography-mass spectrometry methods to identify volatile phenolic compounds released from stressed viceroy butterflies. In both approaches, all structures were characterized based on their mass spectral fragmentation patterns and confirmed with authentic standards. The phenolics we found are known to deter predator attack in other prey systems, including other willow-feeding insect species. Because these compounds have a generalized defensive function at the concentrations we described, our results are consistent with the Müllerian reclassification put forth by other researchers based on bioassay results. It seems that the viceroy butterfly possesses chemical defenses different from its monarch and queen butterfly counterparts (phenolic glycosides vs. cardiac glycosides, respectively), an unusual phenomenon in mimicry warranting future study.

Chlamydia trachomatis Is Resistant to Inclusion Ubiquitination and Associated Host Defense in Gamma Interferon-Primed Human Epithelial Cells.

PubMed

Haldar, Arun K; Piro, Anthony S; Finethy, Ryan; Espenschied, Scott T; Brown, Hannah E; Giebel, Amanda M; Frickel, Eva-Maria; Nelson, David E; Coers, Jörn

2016-12-13

The cytokine gamma interferon (IFN-γ) induces cell-autonomous immunity to combat infections with intracellular pathogens, such as the bacterium Chlamydia trachomatis The present study demonstrates that IFN-γ-primed human cells ubiquitinate and eliminate intracellular Chlamydia-containing vacuoles, so-called inclusions. We previously described how IFN-γ-inducible immunity-related GTPases (IRGs) employ ubiquitin systems to mark inclusions for destruction in mouse cells and, furthermore, showed that the rodent pathogen Chlamydia muridarum blocks ubiquitination of its inclusions by interfering with mouse IRG function. Here, we report that ubiquitination of inclusions in human cells is independent of IRG and thus distinct from the murine pathway. We show that C. muridarum is susceptible to inclusion ubiquitination in human cells, while the closely related human pathogen C. trachomatis is resistant. C. muridarum, but not C. trachomatis, inclusions attract several markers of cell-autonomous immunity, including the ubiquitin-binding protein p62, the ubiquitin-like protein LC3, and guanylate-binding protein 1. Consequently, we find that IFN-γ priming of human epithelial cells triggers the elimination of C. muridarum, but not C. trachomatis, inclusions. This newly described defense pathway is independent of indole-2,3-dioxygenase, a known IFN-γ-inducible anti-Chlamydia resistance factor. Collectively, our observations indicate that C. trachomatis evolved mechanisms to avoid a human-specific, ubiquitin-mediated response as part of its unique adaptation to its human host. Chlamydia trachomatis is the leading cause of sexually transmitted bacterial infections and responsible for significant morbidity, including pelvic inflammatory disease, infertility, and ectopic pregnancies in women. As an obligate intracellular pathogen, C. trachomatis is in perpetual conflict with cell-intrinsic defense programs executed by its human host. Our study defines a novel anti

Aspergillus flavus induced alterations in tear protein profile reveal pathogen-induced host response to fungal infection.

PubMed

Kandhavelu, Jeyalakshmi; Demonte, Naveen Luke; Namperumalsamy, Venkatesh Prajna; Prajna, Lalitha; Thangavel, Chitra; Jayapal, Jeya Maheshwari; Kuppamuthu, Dharmalingam

2017-01-30

Aspergillus flavus and Fusarium sp. are primary causative agents of keratitis that results in corneal tissue damage leading to vision loss particularly in individuals from the tropical parts of the world. Proteins in the tear film collected from control and keratitis patients was profiled and compared. A total of 1873 proteins from control and 1400 proteins from patient tear were identified by mass spectrometry. While 847 proteins were found to be glycosylated in the patient tear, only 726 were glycosylated in control tear. And, some of the tear proteins showed alterations in their glycosylation pattern after infection. Complement system proteins, proteins specific for neutrophil extracellular traps and proteins involved in would healing were found only in the patient tear. The presence of these innate immune system proteins in the tear film of patients supports the previous data indicating the involvement of neutrophil and complement pathways in antifungal defense. High levels of wound healing proteins in keratitis patient tear implied activation of tissue repair during infection. The early appearance of the host defense proteins and wound healing response indicates that tear proteins could be used as an early marker system for monitoring the progression of pathogenesis. Identification of negative regulators of the above defense pathways in keratitis tear indicates an intricate balance of pro and anti-defense mechanisms operating in fungal infection of the eye. Tear proteins from control and mycotic keratitis patients were separated into glycoproteins and non-glycosylated proteins and then identified by mass spectrometry. Tear proteins from keratitis patients showed alteration in the glycosylation pattern indicating the alteration of glycosylation machinery due to infection. Neutrophil extracellular traps specific proteins, complement pathway proteins, as well as wound healing proteins, were found only in patient tear showing the activation of antifungal defense

Bemisia tabaci Q carrying tomato yellow leaf curl virus strongly suppresses host plant defenses

PubMed Central

Shi, Xiaobin; Pan, Huipeng; Zhang, Hongyi; Jiao, Xiaoguo; Xie, Wen; Wu, Qingjun; Wang, Shaoli; Fang, Yong; Chen, Gong; Zhou, Xuguo; Zhang, Youjun

2014-01-01

The concurrence of tomato yellow leaf curl virus (TYLCV) with the spread of its vector Bemisia tabaci Q rather than B in China suggests a more mutualistic relationship between TYLCV and Q. Here, we investigated the hypothesis that viruliferous B and Q have different effects on plant defenses. We found the fecundity of nonviruliferous B, nonviruliferous Q, viruliferous Q and viruliferous B was 11.080, 12.060, 10.760, and 11.220 respectively on plants previously attacked by the other biotype, however, on their respective noninfested control leaves fecundity was 12.000, 10.880, 9.760, and 8.020 respectively. Only viruliferous B had higher fecundity on viruliferous Q-infested plants than on control plants. The longevity of viruliferous B showed the same phenomenon. At 1 d infestion, the jasmonic acid content in leaves noninfested and in leaves infested with nonviruliferous B, nonviruliferous Q, viruliferous B and viruliferous Q was 407.000, 281.333, 301.333, 266.667 and 134.000 ng/g FW, respectively. The JA content was lowest in viruliferous Q-infested leaves. The proteinase inhibitor activity and expression of JA-related upstream gene LOX and downstream gene PI II showed the same trend. The substantial suppression of host defenses by Q carrying TYLCV probably enhances the spread of Q and TYLCV in China. PMID:24912756

Shared weapons of blood- and plant-feeding insects: Surprising commonalities for manipulating hosts.

PubMed

Guiguet, Antoine; Dubreuil, Géraldine; Harris, Marion O; Appel, Heidi M; Schultz, Jack C; Pereira, Marcos H; Giron, David

2016-01-01

Insects that reprogram host plants during colonization remind us that the insect side of plant-insect story is just as interesting as the plant side. Insect effectors secreted by the salivary glands play an important role in plant reprogramming. Recent discoveries point to large numbers of salivary effectors being produced by a single herbivore species. Since genetic and functional characterization of effectors is an arduous task, narrowing the field of candidates is useful. We present ideas about types and functions of effectors from research on blood-feeding parasites and their mammalian hosts. Because of their importance for human health, blood-feeding parasites have more tools from genomics and other - omics than plant-feeding parasites. Four themes have emerged: (1) mechanical damage resulting from attack by blood-feeding parasites triggers "early danger signals" in mammalian hosts, which are mediated by eATP, calcium, and hydrogen peroxide, (2) mammalian hosts need to modulate their immune responses to the three "early danger signals" and use apyrases, calreticulins, and peroxiredoxins, respectively, to achieve this, (3) blood-feeding parasites, like their mammalian hosts, rely on some of the same "early danger signals" and modulate their immune responses using the same proteins, and (4) blood-feeding parasites deploy apyrases, calreticulins, and peroxiredoxins in their saliva to manipulate the "danger signals" of their mammalian hosts. We review emerging evidence that plant-feeding insects also interfere with "early danger signals" of their hosts by deploying apyrases, calreticulins and peroxiredoxins in saliva. Given emerging links between these molecules, and plant growth and defense, we propose that these effectors interfere with phytohormone signaling, and therefore have a special importance for gall-inducing and leaf-mining insects, which manipulate host-plants to create better food and shelter. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evasion of Human Neutrophil-Mediated Host Defense during Toxoplasma gondii Infection

PubMed Central

Lima, Tatiane S.; Gov, Lanny

2018-01-01

ABSTRACT Neutrophils are a major player in host immunity to infection; however, the mechanisms by which human neutrophils respond to the intracellular protozoan parasite Toxoplasma gondii are still poorly understood. In the current study, we found that, whereas primary human monocytes produced interleukin-1beta (IL-1β) in response to T. gondii infection, human neutrophils from the same blood donors did not. Moreover, T. gondii inhibited lipopolysaccharide (LPS)-induced IL-1β synthesis in human peripheral blood neutrophils. IL-1β suppression required active parasite invasion, since heat-killed or mycalolide B-treated parasites did not inhibit IL-1β release. By investigating the mechanisms involved in this process, we found that T. gondii infection of neutrophils treated with LPS resulted in reduced transcript levels of IL-1β and NLRP3 and reduced protein levels of pro-IL-1β, mature IL-1β, and the inflammasome sensor NLRP3. In T. gondii-infected neutrophils stimulated with LPS, the levels of MyD88, TRAF6, IKKα, IKKβ, and phosphorylated IKKα/β were not affected. However, LPS-induced IκBα degradation and p65 phosphorylation were reduced in T. gondii-infected neutrophils, and degradation of IκBα was reversed by treatment with the proteasome inhibitor MG-132. Finally, we observed that T. gondii inhibited the cleavage and activity of caspase-1 in human neutrophils. These results indicate that T. gondii suppression of IL-1β involves a two-pronged strategy whereby T. gondii inhibits both NF-κB signaling and activation of the NLRP3 inflammasome. These findings represent a novel mechanism of T. gondii evasion of human neutrophil-mediated host defense by targeting the production of IL-1β. PMID:29440572

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.

APOBEC3G: a Double Agent in Defense

PubMed Central

Smith, Harold C.

2011-01-01

APOBEC3G (A3G) is an effective cellular host defense factor under experimental conditions in which a functional form of the HIV-encoded protein Vif cannot be expressed. Wild type Vif targets A3G for proteasomal degradation and along with it, any host defense advantage A3G might provide is severely diminished or lost. Recent evidence cast doubt on the potency of A3G in host defense and suggested that it could, under some circumstances, promote the emergence of more virulent HIV strains. In this article, I argue that it is time to recognize that A3G has the potential to act as a double agent. The path forward relies on understanding how cellular and viral regulatory mechanisms enable A3G antiviral function and on developing novel research reagents to explore these pathways. PMID:21239176

Keeping Control: The Role of Senescence and Development in Plant Pathogenesis and Defense

PubMed Central

Häffner, Eva; Konietzki, Sandra; Diederichsen, Elke

2015-01-01

Many plant pathogens show interactions with host development. Pathogens may modify plant development according to their nutritional demands. Conversely, plant development influences pathogen growth. Biotrophic pathogens often delay senescence to keep host cells alive, and resistance is achieved by senescence-like processes in the host. Necrotrophic pathogens promote senescence in the host, and preventing early senescence is a resistance strategy of plants. For hemibiotrophic pathogens both patterns may apply. Most signaling pathways are involved in both developmental and defense reactions. Increasing knowledge about the molecular components allows to distinguish signaling branches, cross-talk and regulatory nodes that may influence the outcome of an infection. In this review, recent reports on major molecular players and their role in senescence and in pathogen response are reviewed. Examples of pathosystems with strong developmental implications illustrate the molecular basis of selected control strategies. A study of gene expression in the interaction between the hemibiotrophic vascular pathogen Verticillium longisporum and its cruciferous hosts shows processes that are fine-tuned to counteract early senescence and to achieve resistance. The complexity of the processes involved reflects the complex genetic control of quantitative disease resistance, and understanding the relationship between disease, development and resistance will support resistance breeding. PMID:27135337

Chytridiomycosis of Marine Diatoms-The Role of Stress Physiology and Resistance in Parasite-Host Recognition and Accumulation of Defense Molecules.

PubMed

Scholz, Bettina; Küpper, Frithjof C; Vyverman, Wim; Ólafsson, Halldór G; Karsten, Ulf

2017-01-25

Little is known about the role of chemotaxis in the location and attachment of chytrid zoospores to potential diatom hosts. Hypothesizing that environmental stress parameters affect parasite-host recognition, four chytrid-diatom tandem cultures ( Chytridium sp./ Navicula sp., Rhizophydium type I/ Nitzschia sp., Rhizophydium type IIa/ Rhizosolenia sp., Rhizophydium type IIb/ Chaetoceros sp.) were used to test the chemotaxis of chytrid zoospores and the presence of potential defense molecules in a non-contact-co-culturing approach. As potential triggers in the chemotaxis experiments, standards of eight carbohydrates, six amino acids, five fatty acids, and three compounds known as compatible solutes were used in individual and mixed solutions, respectively. In all tested cases, the whole-cell extracts of the light-stressed (continuous light exposure combined with 6 h UV radiation) hosts attracted the highest numbers of zoospores (86%), followed by the combined carbohydrate standard solution (76%), while all other compounds acted as weak triggers only. The results of the phytochemical screening, using biomass and supernatant extracts of susceptible and resistant host-diatom cultures, indicated in most of the tested extracts the presence of polyunsaturated fatty acids, phenols, and aldehydes, whereas the bioactivity screenings showed that the zoospores of the chytrid parasites were only significantly affected by the ethanolic supernatant extract of the resistant hosts.

An experimental test of the effects of behavioral and immunological defenses against vectors: do they interact to protect birds from blood parasites?

PubMed Central

2014-01-01

Background Blood-feeding arthropods can harm their hosts in many ways, such as through direct tissue damage and anemia, but also by distracting hosts from foraging or watching for predators. Blood-borne pathogens transmitted by arthropods can further harm the host. Thus, effective behavioral and immunological defenses against blood-feeding arthropods may provide important fitness advantages to hosts if they reduce bites, and in systems involving pathogen transmission, if they lower pathogen transmission rate. Methods We tested whether Rock Pigeons (Columba livia) have effective behavioral and immunological defenses against a blood-feeding hippoboscid fly (Pseudolynchia canariensis) and, if so, whether the two defenses interact. The fly vectors the blood parasite Haemoproteus columbae; we further tested whether these defenses reduced the transmission success of blood parasites when birds were exposed to infected flies. We compared four experimental treatments in which hosts had available both purported defenses, only one of the defenses, or no defenses against the flies. Results We found that preening and immunological defenses were each effective in decreasing the survival and reproductive success of flies. However, the two defenses were additive, rather than one defense enhancing or decreasing the effectiveness of the other defense. Neither defense reduced the prevalence of H. columbae, nor the intensity of infection in birds exposed to infected flies. Conclusions Flies experience reduced fitness when maintained on hosts with immunological or preening defenses. This suggests that if vectors are given a choice among hosts, they may choose hosts that are less defended, which could impact pathogen transmission in a system where vectors can choose among hosts. PMID:24620737

Molecular basis of recognition between phytophthora pathogens and their hosts.

PubMed

Tyler, Brett M

2002-01-01

Recognition is the earliest step in any direct plant-microbe interaction. Recognition between Phytophthora pathogens, which are oomycetes, phylogenetically distinct from fungi, has been studied at two levels. Recognition of the host by the pathogen has focused on recognition of chemical, electrical, and physical features of plant roots by zoospores. Both host-specific factors such as isoflavones, and host-nonspecific factors such as amino acids, calcium, and electrical fields, influence zoospore taxis, encystment, cyst germination, and hyphal chemotropism in guiding the pathogen to potential infection sites. Recognition of the pathogen by the host defense machinery has been analyzed using biochemical and genetic approaches. Biochemical approaches have identified chemical elicitors of host defense responses, and in some cases, their cognate receptors from the host. Some elicitors, such as glucans and fatty acids, have broad host ranges, whereas others such as elicitins have narrow host ranges. Most elicitors identified appear to contribute primarily to basic or nonhost resistance. Genetic analysis has identified host resistance (R) genes and pathogen avirulence (Avr) genes that interact in a gene-for-gene manner. One Phytophthora Avr gene, Avr1b from P. sojae, has been cloned and characterized. It encodes a secreted elicitor that triggers a system-wide defense response in soybean plants carrying the cognate R gene, Rps1b.

Transient Receptor Potential Channel 1 Deficiency Impairs Host Defense and Proinflammatory Responses to Bacterial Infection by Regulating Protein Kinase Cα Signaling.

PubMed

Zhou, Xikun; Ye, Yan; Sun, Yuyang; Li, Xuefeng; Wang, Wenxue; Privratsky, Breanna; Tan, Shirui; Zhou, Zongguang; Huang, Canhua; Wei, Yu-Quan; Birnbaumer, Lutz; Singh, Brij B; Wu, Min

2015-08-01

Transient receptor potential channel 1 (TRPC1) is a nonselective cation channel that is required for Ca(2+) homeostasis necessary for cellular functions. However, whether TRPC1 is involved in infectious disease remains unknown. Here, we report a novel function for TRPC1 in host defense against Gram-negative bacteria. TRPC1(-/-) mice exhibited decreased survival, severe lung injury, and systemic bacterial dissemination upon infection. Furthermore, silencing of TRPC1 showed decreased Ca(2+) entry, reduced proinflammatory cytokines, and lowered bacterial clearance. Importantly, TRPC1 functioned as an endogenous Ca(2+) entry channel critical for proinflammatory cytokine production in both alveolar macrophages and epithelial cells. We further identified that bacterium-mediated activation of TRPC1 was dependent on Toll-like receptor 4 (TLR4), which induced endoplasmic reticulum (ER) store depletion. After activation of phospholipase Cγ (PLC-γ), TRPC1 mediated Ca(2+) entry and triggered protein kinase Cα (PKCα) activity to facilitate nuclear translocation of NF-κB/Jun N-terminal protein kinase (JNK) and augment the proinflammatory response, leading to tissue damage and eventually mortality. These findings reveal that TRPC1 is required for host defense against bacterial infections through the TLR4-TRPC1-PKCα signaling circuit. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

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.

Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.

PubMed

Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael

2016-01-01

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection

PubMed Central

O’Hern, Corey S.; Shattuck, Mark D.; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G.

2016-01-01

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical

Messages from the Other Side: Parasites Receive Damage Cues from their Host Plants.

PubMed

Tjiurutue, Muvari Connie; Stevenson, Philip C; Adler, Lynn S

2016-08-01

As sessile organisms, plants rely on their environment for cues indicating imminent herbivory. These cues can originate from tissues on the same plant or from different individuals. Since parasitic plants form vascular connections with their host, parasites have the potential to receive cues from hosts that allow them to adjust defenses against future herbivory. However, the role of plant communication between hosts and parasites for herbivore defense remains poorly investigated. Here, we examined the effects of damage to lupine hosts (Lupinus texensis) on responses of the attached hemiparasite (Castilleja indivisa), and indirectly, on a specialist herbivore of the parasite, buckeyes (Junonia coenia). Lupines produce alkaloids that act as defenses against herbivores that can be taken up by the parasite. We found that damage to lupine host plants by beet armyworm (Spodoptera exigua) significantly increased jasmonic acid (JA) levels in both the lupine host and parasite, suggesting uptake of phytohormones or priming of parasite defenses by using host cues. However, lupine host damage did not induce changes in alkaloid levels in the hosts or parasites. Interestingly, the parasite had substantially higher concentrations of JA and alkaloids compared to lupine host plants. Buckeye herbivores consumed more parasite tissue when attached to damaged compared to undamaged hosts. We hypothesize that increased JA due to lupine host damage induced higher iridoid glycosides in the parasite, which are feeding stimulants for this specialist herbivore. Our results demonstrate that damage to hosts may affect both parasites and associated herbivores, indicating cascading effects of host damage on multiple trophic levels.

Strategic variation in mobbing as a front line of defense against brood parasitism.

PubMed

Welbergen, Justin A; Davies, Nicholas B

2009-02-10

Coevolutionary arms races, where adaptations in one party select for counter-adaptations in another and vice versa, are fundamental to interactions between organisms and their predators, pathogens, and parasites [1]. Avian brood parasites and their hosts have emerged as model systems for studying such reciprocal coevolutionary processes [2, 3]. For example, hosts have evolved changes in egg appearance and rejection of foreign eggs in response to brood parasitism from cuckoos, and cuckoos have evolved host-egg mimicry as a counter-response [4-6]. However, the host's front line of defense is protecting the nest from being parasitized in the first place [7-10], yet little is known about the effectiveness of nest defense as an antiparasite adaptation, and its coevolutionary significance remains poorly understood [10]. Here we show first that mobbing of common cuckoos Cuculus canorus by reed warblers Acrocephalus scirpaceus is an effective defense against parasitism. Second, mobbing of cuckoos is a phenotypically plastic trait that is modified strategically according to local parasitism risk. This supports the view that hosts use a "defense in-depth strategy," with successive flexible lines of defense that coevolve with corresponding offensive lines of the parasite. This highlights the need for more holistic research into the coevolutionary consequences when multiple adaptations and counter-adaptations evolve in concert [11].

Murine respiratory mycoplasmosis (MRM) in C57BL/6N and C3H/HeN mice: strain differences in early host responses and exacerbation by nitrogen dioxide

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

Parker, R.F.

1987-01-01

The studies reported here used genetic differences in susceptibility of C57BL/6N and C3H/HeN mice and exacerbation of the disease by nitrogen dioxide (NO/sub 2/) as tools in assessing the role of early host responses in the pathogenesis of MRM. The two strains did not differ in susceptibility to infection, but C3H/HeN mice were more susceptible to and had increased severity of lung lesions 14 days after intranasal inoculation as determined by 50% biological endpoints and morphometric analysis of tissues. Exposure to NO/sub 2/ for 4 hours prior to exposure to infectious aerosols exacerbated murine respiratory mycoplasmosis (MRM) by 7 daysmore » after exposure in both mouse strains. NO/sub 2/ appeared to affect host lung defense mechanisms responsible for limiting mycoplasmal growth in the lungs. The NO/sub 2/ exposure concentration required for this effect varied with the genetic background of the host, the dose of mycoplasmas administered, and the endpoint measured. Pulmonary clearance of radiolabeled M. pulmonis was determined in both mouse strains, and in C57BL/6N mice exposed to NO/sub 2/.« less

The effect of protective nutrients on mucosal defense in the immature intestine.

PubMed

Forchielli, Maria L; Walker, W Allan

2005-10-01

Oral nutrition plays a dual role in the gut, providing nutrition to the body while affecting the function of the gastrointestinal tract. The exposure of the gut to food antigens, in the form of either beneficial or harmful nutritional substances, contributes to a vast array of physiological and pathologic gastrointestinal responses with secondary systemic implications. The immune system of the gastrointestinal tract is always involved in the first line of defense, and its actions are particularly important in the early period of life as maturation takes place. From maturation, a balance ensues in the regulatory mechanism of host defense, ultimately leading to either tolerance or immune reaction. This paper emphasizes how some nutrients may beneficially affect the gastrointestinal immune system's maturation in both term and especially premature neonates.

Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

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

Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo

Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes inmore » the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.« less

Cost-effective Expression and Purification of Antimicrobial and Host Defense Peptides in Escherichia coli

PubMed Central

Bommarius, B.; Jenssen, H.; Elliott, M.; Kindrachuk, J.; Pasupuleti, Mukesh; Gieren, H; Jaeger, K.-E.; Hancock, R.E. W.

2010-01-01

Cationic antimicrobial host defense peptides (HDPs) combat infection by directly killing a wide variety of microbes, and/or modulating host immunity. HDPs have great therapeutic potential against antibiotic-resistant bacteria, viruses and even parasites, but there are substantial roadblocks to their therapeutic application. High manufacturing costs associated with amino acid precursors have limited the delivery of inexpensive therapeutics through industrial-scale chemical synthesis. Conversely, the production of peptides in bacteria by recombinant DNA technology has been impeded by the antimicrobial activity of these peptides and their susceptibility to proteolytic degradation, while subsequent purification of recombinant peptides often requires multiple steps and has not been cost-effective. Here we have developed methodologies appropriate for large-scale industrial production of HDPs; in particular, we describe (i) a method, using fusions to SUMO, for producing high yields of intact recombinant HDPs in bacteria without significant toxicity; and (ii) a simplified 2-step purification method appropriate for industrial use. We have used this method to produce seven HDPs to date (IDR1, MX226, LL37, CRAMP, HHC-10, E5 and E6). Using this technology, pilot-scale fermentation (10 L) was performed to produce large quantities of biologically active cationic peptides. Together, these data indicate that this new method represents a cost-effective means to enable commercial enterprises to produce HDPs in large-scale under Good Laboratory Manufacturing Practice (GMP) conditions for therapeutic application in humans. PMID:20713107

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

Macrophage defense mechanisms against intracellular bacteria

PubMed Central

Weiss, Günter; Schaible, Ulrich E

2015-01-01

Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

DefenseLink Feature:

Science.gov Websites

Center, Wilberforce, Ohio. Celebrating African American History University Helps DoD Celebrate African -American History University Helps DoD Celebrate African-American History FAYETTEVILLE, N.C., Feb. 29, 2008 Carolina, hosted the Defense Department's 2008 African-American History Month outreach and observance

Research on moving target defense based on SDN

NASA Astrophysics Data System (ADS)

Chen, Mingyong; Wu, Weimin

2017-08-01

An address mutation strategy was proposed. This strategy provided an unpredictable change in address, replacing the real address of the packet forwarding process and path mutation, thus hiding the real address of the host and path. a mobile object defense technology based on Spatio-temporal Mutation on this basis is proposed, Using the software Defined Network centralized control architecture advantage combines sFlow traffic monitoring technology and Moving Target Defense. A mutated time period which can be changed in real time according to the network traffic is changed, and the destination address is changed while the controller abruptly changes the address while the data packet is transferred between the switches to construct a moving target, confusing the host within the network, thereby protecting the host and network.

Dual Role of Act1 in Keratinocyte Differentiation and Host Defense: TRAF3IP2 Silencing Alters Keratinocyte Differentiation and Inhibits IL-17 Responses.

PubMed

Lambert, Sylviane; Swindell, William R; Tsoi, Lam C; Stoll, Stefan W; Elder, James T

2017-07-01

TRAF3IP2 is a candidate psoriasis susceptibility gene encoding Act1, an adaptor protein with ubiquitin ligase activity that couples the IL-17 receptor to downstream signaling pathways. We investigated the role of Act1 in keratinocyte responses to IL-17 using a tetracycline inducible short hairpin RNA targeting TRAF3IP2. Tetracycline exposure for 7 days effectively silenced TRAF3IP2 mRNA and Act1 protein, resulting in 761 genes with significant changes in expression (495 down, 266 up; >1.5-fold, P < 0.05). Gene ontology analysis showed that genes affected by TRAF3IP2 silencing are involved in epidermal differentiation, with early differentiation genes (KRT1, KRT10, DSC1, DSG1) being down-regulated and late differentiation genes (SPRR2, SPRR3, LCE3) being up-regulated. AP1 binding sites were enriched upstream of genes up-regulated by TRAF3IP2 silencing. Correspondingly, nuclear expression of FosB and Fra1 was increased in TRAF3IP2-silenced cells. Many genes involved in host defense were induced by IL-17 in a TRAF3IP2-dependent fashion. Inflammatory differentiation conditions (serum addition for 4 days postconfluence) markedly amplified these IL-17 responses and increased basal levels and TRAF3IP2 silencing-dependent up-regulation of multiple late differentiation genes. These findings suggest that TRAF3IP2 may alter both epidermal homeostasis and keratinocyte defense responses to influence psoriasis risk. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense.

PubMed

Sonoda, Junichiro; Laganière, Josée; Mehl, Isaac R; Barish, Grant D; Chong, Ling-Wa; Li, Xiangli; Scheffler, Immo E; Mock, Dennis C; Bataille, Alain R; Robert, Francois; Lee, Chih-Hao; Giguère, Vincent; Evans, Ronald M

2007-08-01

Macrophage activation by the proinflammatory cytokine interferon-gamma (IFN-gamma) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature of the IFN-gamma-induced activation pathway is not known. Here we show using genome-wide expression and chromatin-binding profiling that IFN-gamma induces the expression of many nuclear genes encoding mitochondrial respiratory chain machinery via activation of the nuclear receptor ERR alpha (estrogen-related receptor alpha, NR3B1). Studies with macrophages lacking ERR alpha demonstrate that it is required for induction of mitochondrial reactive oxygen species (ROS) production and efficient clearance of Listeria monocytogenes (LM) in response to IFN-gamma. As a result, mice lacking ERR alpha are susceptible to LM infection, a phenotype that is localized to bone marrow-derived cells. Furthermore, we found that IFN-gamma-induced activation of ERR alpha depends on coactivator PGC-1 beta (peroxisome proliferator-activated receptor gamma coactivator-1 beta), which appears to be a direct target for the IFN-gamma/STAT-1 signaling cascade. Thus, ERR alpha and PGC-1 beta act together as a key effector of IFN-gamma-induced mitochondrial ROS production and host defense.

The spitting image of plant defenses: effects of plant secondary chemistry on the efficiency of caterpillar regurgitant as an anti-predator defense

USDA-ARS?s Scientific Manuscript database

In the arms race between plants, herbivores, and their natural enemies, specialized herbivores may use plant defenses for their own benefit. In such cases, variation in secondary chemistry among host plants may affect the benefits that herbivores derive from these defenses. Caterpillars of Pieris br...

Tick-Borne Viruses and Biological Processes at the Tick-Host-Virus Interface

PubMed Central

Kazimírová, Mária; Thangamani, Saravanan; Bartíková, Pavlína; Hermance, Meghan; Holíková, Viera; Štibrániová, Iveta; Nuttall, Patricia A.

2017-01-01

Ticks are efficient vectors of arboviruses, although less than 10% of tick species are known to be virus vectors. Most tick-borne viruses (TBV) are RNA viruses some of which cause serious diseases in humans and animals world-wide. Several TBV impacting human or domesticated animal health have been found to emerge or re-emerge recently. In order to survive in nature, TBV must infect and replicate in both vertebrate and tick cells, representing very different physiological environments. Information on molecular mechanisms that allow TBV to switch between infecting and replicating in tick and vertebrate cells is scarce. In general, ticks succeed in completing their blood meal thanks to a plethora of biologically active molecules in their saliva that counteract and modulate different arms of the host defense responses (haemostasis, inflammation, innate and acquired immunity, and wound healing). The transmission of TBV occurs primarily during tick feeding and is a complex process, known to be promoted by tick saliva constituents. However, the underlying molecular mechanisms of TBV transmission are poorly understood. Immunomodulatory properties of tick saliva helping overcome the first line of defense to injury and early interactions at the tick-host skin interface appear to be essential in successful TBV transmission and infection of susceptible vertebrate hosts. The local host skin site of tick attachment, modulated by tick saliva, is an important focus of virus replication. Immunomodulation of the tick attachment site also promotes co-feeding transmission of viruses from infected to non-infected ticks in the absence of host viraemia (non-viraemic transmission). Future research should be aimed at identification of the key tick salivary molecules promoting virus transmission, and a molecular description of tick-host-virus interactions and of tick-mediated skin immunomodulation. Such insights will enable the rationale design of anti-tick vaccines that protect against

Tick-Borne Viruses and Biological Processes at the Tick-Host-Virus Interface.

PubMed

Kazimírová, Mária; Thangamani, Saravanan; Bartíková, Pavlína; Hermance, Meghan; Holíková, Viera; Štibrániová, Iveta; Nuttall, Patricia A

2017-01-01

Ticks are efficient vectors of arboviruses, although less than 10% of tick species are known to be virus vectors. Most tick-borne viruses (TBV) are RNA viruses some of which cause serious diseases in humans and animals world-wide. Several TBV impacting human or domesticated animal health have been found to emerge or re-emerge recently. In order to survive in nature, TBV must infect and replicate in both vertebrate and tick cells, representing very different physiological environments. Information on molecular mechanisms that allow TBV to switch between infecting and replicating in tick and vertebrate cells is scarce. In general, ticks succeed in completing their blood meal thanks to a plethora of biologically active molecules in their saliva that counteract and modulate different arms of the host defense responses (haemostasis, inflammation, innate and acquired immunity, and wound healing). The transmission of TBV occurs primarily during tick feeding and is a complex process, known to be promoted by tick saliva constituents. However, the underlying molecular mechanisms of TBV transmission are poorly understood. Immunomodulatory properties of tick saliva helping overcome the first line of defense to injury and early interactions at the tick-host skin interface appear to be essential in successful TBV transmission and infection of susceptible vertebrate hosts. The local host skin site of tick attachment, modulated by tick saliva, is an important focus of virus replication. Immunomodulation of the tick attachment site also promotes co-feeding transmission of viruses from infected to non-infected ticks in the absence of host viraemia (non-viraemic transmission). Future research should be aimed at identification of the key tick salivary molecules promoting virus transmission, and a molecular description of tick-host-virus interactions and of tick-mediated skin immunomodulation. Such insights will enable the rationale design of anti-tick vaccines that protect against

Nonredundant Roles of Interleukin-17A (IL-17A) and IL-22 in Murine Host Defense against Cutaneous and Hematogenous Infection Due to Methicillin-Resistant Staphylococcus aureus

PubMed Central

Chan, Liana C.; Chaili, Siyang; Filler, Scott G.; Barr, Kevin; Wang, Huiyuan; Kupferwasser, Deborah; Edwards, John E.; Xiong, Yan Q.; Ibrahim, Ashraf S.; Miller, Lloyd S.; Schmidt, Clint S.; Hennessey, John P.

2015-01-01

Staphylococcus aureus is the leading cause of skin and skin structure infections (SSSI) in humans. Moreover, the high frequency of recurring SSSI due to S. aureus, particularly methicillin-resistant S. aureus (MRSA) strains, suggests that infection induces suboptimal anamnestic defenses. The present study addresses the hypothesis that interleukin-17A (IL-17A) and IL-22 play distinct roles in immunity to cutaneous and invasive MRSA infection in a mouse model of SSSI. Mice were treated with specific neutralizing antibodies against IL-17A and/or IL-22 and infected with MRSA, after which the severity of infection and host immune response were determined. Neutralization of either IL-17A or IL-22 reduced T cell and neutrophil infiltration and host defense peptide elaboration in lesions. These events corresponded with increased abscess severity, MRSA viability, and CFU density in skin. Interestingly, combined inhibition of IL-17A and IL-22 did not worsen abscesses but did increase gamma interferon (IFN-γ) expression at these sites. The inhibition of IL-22 led to a reduction in IL-17A expression, but not vice versa. These results suggest that the expression of IL-17A is at least partially dependent on IL-22 in this model. Inhibition of IL-17A but not IL-22 led to hematogenous dissemination to kidneys, which correlated with decreased T cell infiltration in renal tissue. Collectively, these findings indicate that IL-17A and IL-22 have complementary but nonredundant roles in host defense against cutaneous versus hematogenous infection. These insights may support targeted immune enhancement or other novel approaches to address the challenge of MRSA infection. PMID:26351278

The interferon response circuit in antiviral host defense.

PubMed

Haller, O; Weber, F

2009-01-01

Viruses have learned to multiply in the face of a powerful innate and adaptive immune response of the host. They have evolved multiple strategies to evade the interferon (IFN) system which would otherwise limit virus growth at an early stage of infection. IFNs induce the synthesis of a range of antiviral proteins which serve as cell-autonomous intrinsic restriction factors. For example, the dynamin-like MxA GTPase inhibits the multiplication of influenza and bunyaviruses (such as La Crosse virus, Hantaan virus, Rift Valley Fever virus, and Crimean-Congo hemorrhagic fever virus) by binding and sequestering the nucleocapsid protein into large perinuclear complexes. To overcome such intracellular restrictions, virulent viruses either inhibit IFN synthesis, bind and inactivate secreted IFN molecules, block IFN-activated signaling, or disturb the action of IFN-induced antiviral proteins. Many viruses produce specialized proteins to disarm the danger signal or express virulence genes that target members of the IFN regulatory factor family (IRFs) or components of the JAK-STAT signaling pathway. An alternative evasion strategy is based on extreme viral replication speed which out-competes the IFN response. The identification of viral proteins with IFN antagonistic functions has great implications for disease prevention and therapy. Virus mutants lacking IFN antagonistic properties represent safe yet highly immunogenic candidate vaccines. Furthermore, novel drugs intercepting viral IFN-antagonists could be used to disarm the viral intruders.

Spiroplasma infection causes either early or late male killing in Drosophila, depending on maternal host age

NASA Astrophysics Data System (ADS)

Kageyama, Daisuke; Anbutsu, Hisashi; Shimada, Masakazu; Fukatsu, Takema

2007-04-01

Symbiont-induced male-killing phenotypes have been found in a variety of insects. Conventionally, these phenotypes have been divided into two categories according to the timing of action: early male killing at embryonic stages and late male killing at late larval stages. In Drosophila species, endosymbiotic bacteria of the genus Spiroplasma have been known to cause early male killing. Here, we report that a spiroplasma strain normally causing early male killing also induces late male killing depending on the maternal host age: male-specific mortality of larvae and pupae was more frequently observed in the offspring of young females. As the lowest spiroplasma density and occasional male production were also associated with newly emerged females, we proposed the density-dependent hypothesis for the expression of early and late male-killing phenotypes. Our finding suggested that (1) early and late male-killing phenotypes can be caused by the same symbiont and probably by the same mechanism; (2) late male killing may occur as an attenuated expression of early male killing; (3) expression of early and late male-killing phenotypes may be dependent on the symbiont density, and thus, could potentially be affected by the host immunity and regulation; and (4) early male killing and late male killing could be alternative strategies adopted by microbial reproductive manipulators.

PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.

PubMed

Chereddy, Kiran Kumar; Her, Charles-Henry; Comune, Michela; Moia, Claudia; Lopes, Alessandra; Porporato, Paolo E; Vanacker, Julie; Lam, Martin C; Steinstraesser, Lars; Sonveaux, Pierre; Zhu, Huijun; Ferreira, Lino S; Vandermeulen, Gaëlle; Préat, Véronique

2014-11-28

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks

PubMed Central

Flentie, Kelly; Garner, Ashley L.

2016-01-01

Regulating responses to stress is critical for all bacteria, whether they are environmental, commensal, or pathogenic species. For pathogenic bacteria, successful colonization and survival in the host are dependent on adaptation to diverse conditions imposed by the host tissue architecture and the immune response. Once the bacterium senses a hostile environment, it must enact a change in physiology that contributes to the organism's survival strategy. Inappropriate responses have consequences; hence, the execution of the appropriate response is essential for survival of the bacterium in its niche. Stress responses are most often regulated at the level of gene expression and, more specifically, transcription. This minireview focuses on mechanisms of regulating transcription initiation that are required by Mycobacterium tuberculosis to respond to the arsenal of defenses imposed by the host during infection. In particular, we highlight how certain features of M. tuberculosis physiology allow this pathogen to respond swiftly and effectively to host defenses. By enacting highly integrated and coordinated gene expression changes in response to stress, M. tuberculosis is prepared for battle against the host defense and able to persist within the human population. PMID:26883824

Pathogenic bacteria induce colonic PepT1 expression: an implication in host defense response

PubMed Central

Nguyen, Hang Thi Thu; Dalmasso, Guillaume; Powell, Kimberly R.; Yan, Yutao; Bhatt, Shantanu; Kalman, Daniel; Sitaraman, Shanthi; Merlin, Didier

2009-01-01

Background & Aims Expression of the di/tripeptide transporter PepT1 has been observed in the colon under inflammatory conditions, however, the inducing factors and underlying mechanisms remain unknown. Here, we address the effects of pathogenic bacteria on colonic PepT1 expression together with its functional consequences. Methods Human colonic HT29-Cl.19A cells were infected with the attaching and effacing (A/E) enteropathogenic E. coli (EPEC). Wild-type and PepT1 transgenic mice or cultured colonic tissues derived from these mice were infected with Citrobacter rodentium, a murine A/E pathogen related to EPEC. Results EPEC induced PepT1 expression and activity in HT29-Cl.19A cells by intimately attaching to host cells through lipid rafts. Induction of PepT1 expression by EPEC required the transcription factor Cdx2. PepT1 expression reduced binding of EPEC to lipid rafts, as well as activation of NF-κB and MAP kinase and production of IL-8. Accordingly, ex vivo and in vivo experiments revealed that C. rodentium induced colonic PepT1 expression and that, compared to their wild-type counterparts, PepT1 transgenic mice infected with C. rodentium exhibited decreased bacterial colonization, production of pro-inflammatory cytokines, and neutrophil infiltration into the colon. Conclusions Our findings demonstrate a molecular mechanism underlying the regulation of colonic PepT1 expression under pathological conditions and reveal a novel role for PepT1 in host defense via its capacity to modulate bacterial-epithelial interactions and intestinal inflammation. PMID:19549526

Plant Defense against Insect Herbivores

PubMed Central

Fürstenberg-Hägg, Joel; Zagrobelny, Mika; Bak, Søren

2013-01-01

Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar. Insect herbivory induce several internal signals from the wounded tissues, including calcium ion fluxes, phosphorylation cascades and systemic- and jasmonate signaling. These are perceived in undamaged tissues, which thereafter reinforce their defense by producing different, mostly low molecular weight, defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects have adapted to resist plant defenses, and in some cases even sequester the compounds and reuse them in their own defense. Both plant defense and insect adaptation involve metabolic costs, so most plant-insect interactions reach a stand-off, where both host and herbivore survive although their development is suboptimal. PMID:23681010

Steroid Receptor Coactivator 3 Contributes to Host Defense against Enteric Bacteria by Recruiting Neutrophils via Upregulation of CXCL2 Expression.

PubMed

Chen, Wenbo; Lu, Xuqiang; Chen, Yuan; Li, Ming; Mo, Pingli; Tong, Zhangwei; Wang, Wei; Wan, Wei; Su, Guoqiang; Xu, Jianming; Yu, Chundong

2017-02-15

Steroid receptor coactivator 3 (SRC-3) is a transcriptional coactivator that interacts with nuclear receptors and some other transcription factors to enhance their effects on target gene transcription. We reported previously that SRC-3-deficient (SRC-3 -/- ) mice are extremely susceptible to Escherichia coli-induced septic peritonitis as a result of uncontrolled inflammation and a defect in bacterial clearance. In this study, we observed significant upregulation of SRC-3 in colonic epithelial cells in response to Citrobacter rodentium infection. Based on these findings, we hypothesized that SRC-3 is involved in host defense against attaching and effacing bacterial infection. We compared the responses of SRC-3 -/- and wild-type mice to intestinal C. rodentium infection. We found that SRC-3 -/- mice exhibited delayed clearance of C. rodentium and more severe tissue pathology after oral infection with C. rodentium compared with wild-type mice. SRC-3 -/- mice expressed normal antimicrobial peptides in the colons but exhibited delayed recruitment of neutrophils into the colonic mucosa. Accordingly, SRC-3 -/- mice showed a delayed induction of CXCL2 and CXCL5 in colonic epithelial cells, which are responsible for neutrophil recruitment. At the molecular level, we found that SRC-3 can activate the NF-κB signaling pathway to promote CXCL2 expression at the transcriptional level. Collectively, we show that SRC-3 contributes to host defense against enteric bacteria, at least in part via upregulating CXCL2 expression to recruit neutrophils. Copyright © 2017 by The American Association of Immunologists, Inc.

Multitasking antimicrobial peptides, plant development, and host defense against biotic/abiotic stress

USDA-ARS?s Scientific Manuscript database

Crop losses due to pathogens are a major threat to global food security. Plants employ a multilayer defense system against pathogens including use of physical barriers (cell wall), induction of hypersensitive defense response (HR), resistance (R) proteins, and synthesis of antimicrobial peptides (AM...

Evolution of herbivore-induced early defense signaling was shaped by genome-wide duplications in Nicotiana

PubMed Central

Zhou, Wenwu; Brockmöller, Thomas; Ling, Zhihao; Omdahl, Ashton; Baldwin, Ian T; Xu, Shuqing

2016-01-01

Herbivore-induced defenses are widespread, rapidly evolving and relevant for plant fitness. Such induced defenses are often mediated by early defense signaling (EDS) rapidly activated by the perception of herbivore associated elicitors (HAE) that includes transient accumulations of jasmonic acid (JA). Analyzing 60 HAE-induced leaf transcriptomes from closely-related Nicotiana species revealed a key gene co-expression network (M4 module) which is co-activated with the HAE-induced JA accumulations but is elicited independently of JA, as revealed in plants silenced in JA signaling. Functional annotations of the M4 module were consistent with roles in EDS and a newly identified hub gene of the M4 module (NaLRRK1) mediates a negative feedback loop with JA signaling. Phylogenomic analysis revealed preferential gene retention after genome-wide duplications shaped the evolution of HAE-induced EDS in Nicotiana. These results highlight the importance of genome-wide duplications in the evolution of adaptive traits in plants. DOI: http://dx.doi.org/10.7554/eLife.19531.001 PMID:27813478

Bordetella pertussis modulates human macrophage defense gene expression.

PubMed

Valdez, Hugo Alberto; Oviedo, Juan Marcos; Gorgojo, Juan Pablo; Lamberti, Yanina; Rodriguez, Maria Eugenia

2016-08-01

Bordetella pertussis, the etiological agent of whooping cough, still causes outbreaks. We recently found evidence that B. pertussis can survive and even replicate inside human macrophages, indicating that this host cell might serve as a niche for persistence. In this work, we examined the interaction of B. pertussis with a human monocyte cell line (THP-1) that differentiates into macrophages in culture in order to investigate the host cell response to the infection and the mechanisms that promote that intracellular survival. To that end, we investigated the expression profile of a selected number of genes involved in cellular bactericidal activity and the inflammatory response during the early and late phases of infection. The bactericidal and inflammatory response of infected macrophages was progressively downregulated, while the number of THP-1 cells heavily loaded with live bacteria increased over time postinfection. Two of the main toxins of B. pertussis, pertussis toxin (Ptx) and adenylate cyclase (CyaA), were found to be involved in manipulating the host cell response. Therefore, failure to express either toxin proved detrimental to the development of intracellular infections by those bacteria. Taken together, these results support the relevance of host defense gene manipulation to the outcome of the interaction between B. pertussis and macrophages. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ponderosa pine resin defenses and growth: Metrics matter

Treesearch

Sharon Hood; Anna Sala

2015-01-01

Bark beetles (Coleoptera: Curculionidae, Scolytinae) cause widespread tree mortality in coniferous forests worldwide. Constitutive and induced host defenses are important factors in an individual tree’s ability to survive an attack and in bottom-up regulation of bark beetle population dynamics, yet quantifying defense levels is often difficult. For example, in...

A miniature mimic of host defense peptides with systemic antibacterial efficacy

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

Sarig, Hadar; Livne, Liran; Held-Kuznetsov, Victoria

Oligomers of acylated lysines (OAKs) are synthetic mimics of host defense peptides (HDPs) with promising antimicrobial properties. Here we challenged the OAK concept for its ability to generate both systemically efficient and economically viable lead compounds for fighting multidrug-resistant bacteria. We describe the design and characterization of a miniature OAK composed of only 3 lysyls and 2 acyls (designated C{sub 12({omega}7)}K-{beta}{sub 12}) that preferentially targets gram-positive species by a bacteriostatic mode of action. To gain insight into the mechanism of action, we examined the interaction of OAK with various potential targets, including phospholipid bilayers, using surface plasmon resonance, and Langmuirmore » monolayers, using insertion assays, epifluorescence microscopy, and grazing incidence X-ray diffraction, in a complementary manner. Collectively, the data support the notion that C{sub 12({omega}7)}K-{beta}{sub 12} damages the plasma-membrane architecture similarly to HDPs, that is, following a near-classic 2-step interaction including high-affinity electrostatic adhesion and a subsequent shallow insertion that was limited to the phospholipid head group region. Notably, preliminary acute toxicity and efficacy studies performed with mouse models of infection have consolidated the potential of OAK for treating bacterial infections, including systemic treatments of methicillin-resistant Staphylococcus aureus. Such simple yet robust chemicals might be useful for various antibacterial applications while circumventing potential adverse effects associated with cytolytic compounds.« less

Entamoeba histolytica-Induced Mucin Exocytosis Is Mediated by VAMP8 and Is Critical in Mucosal Innate Host Defense.

PubMed

Cornick, Steve; Moreau, France; Gaisano, Herbert Y; Chadee, Kris

2017-10-03

Intestinal mucus secretion is critical in maintaining mucosal host defense against a myriad of pathogens by preventing direct association with the epithelium. Entamoeba histolytica specifically binds colonic MUC2 mucin and also induces potent hypersecretion from goblet cells; however, characterization of the nature of the mechanisms controlling mucus release remains elusive. In this report, we identify vesicle SNARE vesicle-associated membrane protein 8 (VAMP8) present on mucin granules as orchestrating regulated exocytosis in human goblet cells in response to the presence of E. histolytica VAMP8 was specifically activated during E. histolytica infection, and ablation of VAMP8 led to impaired mucin secretion. As a consequence, loss of VAMP8 increased E. histolytica adherence to epithelial cells associated with enhanced cell death through apoptosis characterized by caspase 3 and 9 cleavages and DNA fragmentation. With the mucosal barrier compromised in Vamp8 -/- animals, E. histolytica induced an aggressive proinflammatory response with elevated levels of interleukin-1 alpha (IL-1α), IL-1β, and tumor necrosis factor alpha (TNF-α) secretion. This report is the first to characterize regulated mucin exocytosis in intestinal goblet cells in response to a pathogen and the downstream consequences of improper mucin secretion in mucosal barrier defense. IMPORTANCE The intestinal tract is exposed to countless substances and pathogens, and yet homeostasis is maintained, in part by the mucus layer that houses the microbiota and spatially separates potential threats from the underlying single layer of epithelium. Despite the critical role of mucus in innate host defense, characterization of the mechanisms by which mucus is secreted from specialized goblet cells in the gut remains elusive. Here, we describe the machinery that regulates mucus secretion as well as the consequence during infection with the colonic pathogen Entamoeba histolytica Abolishment of the key

Interplay between Candida albicans and the Mammalian Innate Host Defense

PubMed Central

Cheng, Shih-Chin; Joosten, Leo A. B.; Kullberg, Bart-Jan

2012-01-01

Candida albicans is both the most common fungal commensal microorganism in healthy individuals and the major fungal pathogen causing high mortality in at-risk populations, especially immunocompromised patients. In this review, we summarize the interplay between the host innate system and C. albicans, ranging from how the host recognizes, responds, and clears C. albicans infection to how C. albicans evades, dampens, and escapes from host innate immunity. PMID:22252867

RING-Domain E3 Ligase-Mediated Host–Virus Interactions: Orchestrating Immune Responses by the Host and Antagonizing Immune Defense by Viruses

PubMed Central

Zhang, Yuexiu; Li, Lian-Feng; Munir, Muhammad; Qiu, Hua-Ji

2018-01-01

The RING-domain E3 ligases (RING E3s), a group of E3 ligases containing one or two RING finger domains, are involved in various cellular processes such as cell proliferation, immune regulation, apoptosis, among others. In the host, a substantial number of the RING E3s have been implicated to inhibit viral replication through regulating immune responses, including activation and inhibition of retinoic acid-inducible gene I-like receptors, toll-like receptors, and DNA receptor signaling pathways, modulation of cell-surface expression of major histocompatibility complex, and co-stimulatory molecules. During the course of evolution and adaptation, viruses encode RING E3s to antagonize host immune defense, such as the infected cell protein 0 of herpes simplex virus type 1, the non-structural protein 1 of rotavirus, and the K3 and K5 of Kaposi’s sarcoma-associated herpesvirus. In addition, recent studies suggest that viruses can hijack the host RING E3s to facilitate viral replication. Based on emerging and interesting discoveries, the RING E3s present novel links among the host and viruses. Herein, we focus on the latest research progresses in the RING E3s-mediated host–virus interactions and discuss the outlooks of the RING E3s for future research. PMID:29872431

Plants versus Fungi and Oomycetes: Pathogenesis, Defense and Counter-Defense in the Proteomics Era

PubMed Central

El Hadrami, Abdelbasset; El-Bebany, Ahmed F.; Yao, Zhen; Adam, Lorne R.; El Hadrami, Ismailx; Daayf, Fouad

2012-01-01

Plant-fungi and plant-oomycete interactions have been studied at the proteomic level for many decades. However, it is only in the last few years, with the development of new approaches, combined with bioinformatics data mining tools, gel staining, and analytical instruments, such as 2D-PAGE/nanoflow-LC-MS/MS, that proteomic approaches thrived. They allow screening and analysis, at the sub-cellular level, of peptides and proteins resulting from plants, pathogens, and their interactions. They also highlight post-translational modifications to proteins, e.g., glycosylation, phosphorylation or cleavage. However, many challenges are encountered during in planta studies aimed at stressing details of host defenses and fungal and oomycete pathogenicity determinants during interactions. Dissecting the mechanisms of such host-pathogen systems, including pathogen counter-defenses, will ensure a step ahead towards understanding current outcomes of interactions from a co-evolutionary point of view, and eventually move a step forward in building more durable strategies for management of diseases caused by fungi and oomycetes. Unraveling intricacies of more complex proteomic interactions that involve additional microbes, i.e., PGPRs and symbiotic fungi, which strengthen plant defenses will generate valuable information on how pathosystems actually function in nature, and thereby provide clues to solving disease problems that engender major losses in crops every year. PMID:22837691

Plants versus fungi and oomycetes: pathogenesis, defense and counter-defense in the proteomics era.

PubMed

El Hadrami, Abdelbasset; El-Bebany, Ahmed F; Yao, Zhen; Adam, Lorne R; El Hadrami, Ismailx; Daayf, Fouad

2012-01-01

Plant-fungi and plant-oomycete interactions have been studied at the proteomic level for many decades. However, it is only in the last few years, with the development of new approaches, combined with bioinformatics data mining tools, gel staining, and analytical instruments, such as 2D-PAGE/nanoflow-LC-MS/MS, that proteomic approaches thrived. They allow screening and analysis, at the sub-cellular level, of peptides and proteins resulting from plants, pathogens, and their interactions. They also highlight post-translational modifications to proteins, e.g., glycosylation, phosphorylation or cleavage. However, many challenges are encountered during in planta studies aimed at stressing details of host defenses and fungal and oomycete pathogenicity determinants during interactions. Dissecting the mechanisms of such host-pathogen systems, including pathogen counter-defenses, will ensure a step ahead towards understanding current outcomes of interactions from a co-evolutionary point of view, and eventually move a step forward in building more durable strategies for management of diseases caused by fungi and oomycetes. Unraveling intricacies of more complex proteomic interactions that involve additional microbes, i.e., PGPRs and symbiotic fungi, which strengthen plant defenses will generate valuable information on how pathosystems actually function in nature, and thereby provide clues to solving disease problems that engender major losses in crops every year.

Diverse host feeding on nesting birds may limit early-season West Nile virus amplification.

PubMed

Egizi, Andrea M; Farajollahi, Ary; Fonseca, Dina M

2014-06-01

Arboviral activity tracks vector availability, which in temperate regions means that transmission ceases during the winter and must be restarted each spring. In the northeastern United States, Culex restuans Theobald resumes its activity earlier than Culex pipiens L. and is thought to be important in restarting West Nile virus (WNV) transmission. Its role in WNV amplification, however, is unclear, because viral levels commonly remain low until the rise of Cx. pipiens later in the season. Because a vector's feeding habits can reveal key information about disease transmission, we identified early-season (April-June) blood meals from Cx. restuans collected throughout New Jersey, and compared them to published datasets from later in the season and also from other parts of the country. We found significantly higher avian diversity, including poor WNV hosts, and fewer blood meals derived from American Robins (17% versus over 40% found in later season). Critically, we identified blood meals from significantly more female than male birds in species where females are the incubating sex, suggesting that Cx. restuans is able to feed on such a wide variety of hosts in early spring because incubating birds are easy targets. Because WNV amplification depends on virus consistently reaching competent hosts, our results indicate that Cx. restuans is unlikely to be an amplifying vector of WNV in the early season. As the season progresses, however, changes in the availability of nesting birds may make it just as capable as Cx. pipiens, although at somewhat lower abundance as the summer progresses.

Cranberry Resistance to Dodder Parasitism: Induced Chemical Defenses and Behavior of a Parasitic Plant.

PubMed

Tjiurutue, Muvari Connie; Sandler, Hilary A; Kersch-Becker, Monica F; Theis, Nina; Adler, Lynn A

2016-02-01

Parasitic plants are common in many ecosystems, where they can structure community interactions and cause major economic damage. For example, parasitic dodder (Cuscuta spp.) can cause up to 80-100 % yield loss in heavily infested cranberry (Vaccinium macrocarpon) patches. Despite their ecological and economic importance, remarkably little is known about how parasitic plants affect, or are affected by, host chemistry. To examine chemically-mediated interactions between dodder and its cranberry host, we conducted a greenhouse experiment asking whether: (1) dodder performance varies with cranberry cultivar; (2) cultivars differ in levels of phytohormones, volatiles, or phenolics, and whether such variation correlates with dodder parasitism; (3) dodder parasitism induced changes in phytohormones, volatiles, or phenolics, and whether the level of inducible response varied among cultivars. We used five cranberry cultivars to assess host attractiveness to dodder and dodder performance. Dodder performance did not differ across cultivars, but there were marginally significant differences in host attractiveness to dodder, with fewer dodder attaching to Early Black than to any other cultivar. Dodder parasitism induced higher levels of salicylic acid (SA) across cultivars. Cultivars differed in overall levels of flavonols and volatile profiles, but not phenolic acids or proanthocyanidins, and dodder attachment induced changes in several flavonols and volatiles. While cultivars differed slightly in resistance to dodder attachment, we did not find evidence of chemical defenses that mediate these interactions. However, induction of several defenses indicates that parasitism alters traits that could influence subsequent interactions with other species, thus shaping community dynamics.

The Interaction of Pneumocystis with the C-Type Lectin Receptor Mincle Exerts a Significant Role in Host Defense Against Infection

PubMed Central

Kottom, Theodore J.; Hebrink, Deanne M.; Jenson, Paige E.; Nandakumar, Vijayalakshmi; Wüthrich, Marcel; Wang, Huafeng; Klein, Bruce; Yamasaki, Sho; Lepenies, Bernd; Limper, Andrew H.

2017-01-01

Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality within immunocompromised patients. In this study, we examined the potential role of Mincle (Macrophage inducible C-type lectin) for host defense against Pneumocystis. Binding assays implementing soluble Mincle Carbohydrate Recognition Domain (CRD) fusion proteins demonstrated binding to intact Pneumocystis carinii (Pc) as well as to organism homogenates, and purified major surface glycoprotein/glycoprotein A derived from the organism. Additional experiments showed that rats with Pneumocystis pneumonia (PCP) expressed increased Mincle mRNA levels. Mouse macrophages over-expressing Mincle displayed increased binding to Pc life forms and enhanced protein tyrosine phosphorylation. The binding of Pc to Mincle resulted in activation of Fc receptor γ (FcRγ) mediated cell signaling. RNA silencing of Mincle in mouse macrophages resulted in decreased activation of Syk kinase after Pc challenge, critical in downstream inflammatory signaling. Mincle deficient CD-4 depleted (Mincle−/−) mice showing a significant defect in organism clearance from the lungs with higher organism burdens and altered lung cytokine responses during Pneumocystis murina (Pm) pneumonia. Interestingly, Mincle−/− did not demonstrate worsened survival during PCP compared to wild type mice, despite the markedly increased organism burdens. This may be related to increased expression of anti-inflammatory factors such as IL-1Ra during infection in the Mincle−/− mice. Of note, the Pm infected Mincle−/− mice demonstrated increased expression of known C-type lectin receptors Dectin-1, Dectin-2, and MCL compared to infected wild type mice. Taken together, these data support a significant role for Mincle in Pneumocystis modulating host defense during infection. PMID:28298521

Racial disparity in survival from early breast cancer in the department of defense healthcare system.

PubMed

Rizzo, Julie A; Sherman, William E; Arciero, Cletus A

2015-06-01

Racial disparity is often identified as a factor in survival from breast cancer in the United States. Current data regarding survival in patients treated in the Department of Defense Military Healthcare System is lacking. The Department of Defense Automated Central Tumor Registry (ACTUR) was queried for all women diagnosed with Stage I or II breast cancer from January 1, 1996 through December 31, 2008. Statistical analyses evaluated demographics, surgical treatment, tumor stage, and survival rates. There were 8,890 patients meeting inclusion criteria. Patients who were younger, Asian American (versus white or black), lower T and/or N stage had significantly improved survival rates. Interestingly, white and black patients demonstrated similar survival in this study. Patients with a longer period of time between diagnosis and treatment had no decrement in survival. As would be expected, patients with a longer recurrence free period enjoyed longer survival. Survival from early stage breast cancer is equivalent between white and black patients in the Department of Defense Healthcare System. This finding is contrary to reports from our civilian counterparts and may be indicative of improved access to care and overall improved cancer surveillance. © 2015 Wiley Periodicals, Inc.

Staphylococcus aureus Manipulates Innate Immunity through Own and Host-Expressed Proteases.

PubMed

Pietrocola, Giampiero; Nobile, Giulia; Rindi, Simonetta; Speziale, Pietro

2017-01-01

Neutrophils, complement system and skin collectively represent the main elements of the innate immune system, the first line of defense of the host against many common microorganisms. Bacterial pathogens have evolved strategies to counteract all these defense activities. Specifically, Staphylococcus aureus , a major human pathogen, secretes a variety of immune evasion molecules including proteases, which cleave components of the innate immune system or disrupt the integrity of extracellular matrix and intercellular connections of tissues. Additionally, S. aureus secretes proteins that can activate host zymogens which, in turn, target specific defense components. Secreted proteins can also inhibit the anti-bacterial function of neutrophils or complement system proteases, potentiating S. aureus chances of survival. Here, we review the current understanding of these proteases and modulators of host proteases in the functioning of innate immunity and describe the importance of these mechanisms in the pathology of staphylococcal diseases.

Staphylococcus aureus Manipulates Innate Immunity through Own and Host-Expressed Proteases

PubMed Central

Pietrocola, Giampiero; Nobile, Giulia; Rindi, Simonetta; Speziale, Pietro

2017-01-01

Neutrophils, complement system and skin collectively represent the main elements of the innate immune system, the first line of defense of the host against many common microorganisms. Bacterial pathogens have evolved strategies to counteract all these defense activities. Specifically, Staphylococcus aureus, a major human pathogen, secretes a variety of immune evasion molecules including proteases, which cleave components of the innate immune system or disrupt the integrity of extracellular matrix and intercellular connections of tissues. Additionally, S. aureus secretes proteins that can activate host zymogens which, in turn, target specific defense components. Secreted proteins can also inhibit the anti-bacterial function of neutrophils or complement system proteases, potentiating S. aureus chances of survival. Here, we review the current understanding of these proteases and modulators of host proteases in the functioning of innate immunity and describe the importance of these mechanisms in the pathology of staphylococcal diseases. PMID:28529927

Friends or Foes? Host defense (antimicrobial) peptides and proteins in human skin diseases.

PubMed

Niyonsaba, François; Kiatsurayanon, Chanisa; Chieosilapatham, Panjit; Ogawa, Hideoki

2017-11-01

Host defense peptides/proteins (HDPs), also known as antimicrobial peptides/proteins (AMPs), are key molecules in the cutaneous innate immune system. AMPs/HDPs historically exhibit broad-spectrum killing activity against bacteria, enveloped viruses, fungi and several parasites. Recently, AMPs/HDPs were shown to have important biological functions, including inducing cell proliferation, migration and differentiation; regulating inflammatory responses; controlling the production of various cytokines/chemokines; promoting wound healing; and improving skin barrier function. Despite the fact that AMPs/HDPs protect our body, several studies have hypothesized that these molecules actively contribute to the pathogenesis of various skin diseases. For example, AMPs/HDPs play crucial roles in the pathological processes of psoriasis, atopic dermatitis, rosacea, acne vulgaris, systemic lupus erythematosus and systemic sclerosis. Thus, AMPs/HDPs may be a double-edged sword, promoting cutaneous immunity while simultaneously initiating the pathogenesis of some skin disorders. This review will describe the most common skin-derived AMPs/HDPs (defensins, cathelicidins, S100 proteins, ribonucleases and dermcidin) and discuss the biology and both the positive and negative aspects of these AMPs/HDPs in skin inflammatory/infectious diseases. Understanding the regulation, functions and mechanisms of AMPs/HDPs may offer new therapeutic opportunities in the treatment of various skin disorders. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of early developmental stages of Myxobolus cerebralis in fish and tubificid oligochaete hosts by in situ hybridization.

PubMed

Antonio, D B; El-Matbouli, M; Hedrick, R P

1999-11-01

The myxosporean and actinosporean spores of Myxobolus cerebralis develop through many stages in their respective hosts, salmonid fishes and a tubificid oligochaete. Using a modified, non-radioactive in situ hybridization protocol, the parasite, which exhibits radically different structural forms during its development in each host, could be specifically detected in paraffin-embedded tissues of both fish and oligochaetes. Our study aims to demonstrate the application of the technique for detection of early stages of M. cerebralis in both hosts.

The AMPK-PPARGC1A pathway is required for antimicrobial host defense through activation of autophagy.

PubMed

Yang, Chul-Su; Kim, Jwa-Jin; Lee, Hye-Mi; Jin, Hyo Sun; Lee, Sang-Hee; Park, Ji-Hoon; Kim, Soung Jung; Kim, Jin-Man; Han, Yong-Mahn; Lee, Myung-Shik; Kweon, Gi Ryang; Shong, Minho; Jo, Eun-Kyeong

2014-05-01

AMP-activated protein kinase (AMPK) is a crucial energy sensor and plays a key role in integration of cellular functions to maintain homeostasis. Despite this, it is largely unknown whether targeting the AMPK pathway can be used as a therapeutic strategy for infectious diseases. Herein, we show that AMPK activation robustly induces antibacterial autophagy, which contributes to antimicrobial defense against Mycobacterium tuberculosis (Mtb). AMPK activation led to inhibition of Mtb-induced phosphorylation of the mechanistic target of rapamycin (MTOR) in macrophages. In addition, AMPK activation increased the genes involved in oxidative phosphorylation, mitochondrial ATP production, and biogenesis in Mtb-infected macrophages. Notably, peroxisome proliferator-activated receptor-gamma, coactivator 1α (PPARGC1A) was required for AMPK-mediated antimicrobial activity, as well as enhancement of mitochondrial function and biogenesis, in macrophages. Further, the AMPK-PPARGC1A pathway was involved in the upregulation of multiple autophagy-related genes via CCAAT/enhancer binding protein (C/EBP), β (CEBPB). PPARGC1A knockdown inhibited the AMPK-mediated induction of autophagy and impaired the fusion of phagosomes with MAP1LC3B (LC3B) autophagosomes in Mtb-infected macrophages. The link between autophagy, mitochondrial function, and antimicrobial activity was further demonstrated by studying LysMCre-mediated knockout of atg7, demonstrating mitochondrial ultrastructural defects and dysfunction, as well as blockade of antimicrobial activity against mycobacteria. Collectively, our results identify the AMPK-PPARGC1A axis as contributing to autophagy activation leading to an antimicrobial response, as a novel host defense mechanism.

Host-Defense Peptides with Therapeutic Potential from Skin Secretions of Frogs from the Family Pipidae

PubMed Central

Conlon, J. Michael; Mechkarska, Milena

2014-01-01

Skin secretions from frogs belonging to the genera Xenopus, Silurana, Hymenochirus, and Pseudhymenochirus in the family Pipidae are a rich source of host-defense peptides with varying degrees of antimicrobial activities and cytotoxicities to mammalian cells. Magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and xenopsin-precursor fragment (XPF) peptides have been isolated from norepinephrine-stimulated skin secretions from several species of Xenopus and Silurana. Hymenochirins and pseudhymenochirins have been isolated from Hymenochirus boettgeri and Pseudhymenochirus merlini. A major obstacle to the development of these peptides as anti-infective agents is their hemolytic activities against human erythrocytes. Analogs of the magainins, CPF peptides and hymenochirin-1B with increased antimicrobial potencies and low cytotoxicities have been developed that are active (MIC < 5 μM) against multidrug-resistant clinical isolates of Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Klebsiella pneumoniae. Despite this, the therapeutic potential of frog skin peptides as anti-infective agents has not been realized so that alternative clinical applications as anti-cancer, anti-viral, anti-diabetic, or immunomodulatory drugs are being explored. PMID:24434793

Context Dependency of a Marine Defensive Symbiosis over a Wide Geographic Distribution

NASA Astrophysics Data System (ADS)

Lopanik, N.; Linneman, J.; Mathew, M.

2016-02-01

The invasive, temperate marine bryozoan Bugula neritina possesses an uncultured, vertically-transmitted bacterial symbiont that produces natural products known as bryostatins. These unpalatable polyketides protect the host larvae from predation. In the western Atlantic, two host genotypes were thought to be restricted to differing latitudes based on the presence of the defensive symbiont: undefended aposymbiotic Type N animals were found at high latitudes, while defended symbiotic Type S colonies were found at low latitudes, where predation pressure is higher. We found that the host genotypes are more widespread than previously thought, but that the symbiont appeared to be restricted to hosts at lower latitudes, regardless of host phylotype, leading to the question of what factors are involved in restricting the symbiont's range. We performed reciprocal transplant experiments of symbiotic and antibiotic-cured hosts, and measured host growth, a proxy for fitness. Our data indicate that possession of the symbiont appears to present a physiological cost to the host. This cost may be more pronounced at higher latitudes where the benefit of symbiosis is less apparent. In addition, preliminary evidence suggests that symbiont titer in a Type S colony from North Carolina transplanted to Virginia is reduced over a period of nearly 4 months. Taken together, these results suggest that a combination of factors may play a role in the distribution of the defensive symbiont: (i) hosts that possess the symbiont are outcompeted by aposymbiotic conspecifics at high latitude and reduced levels of predation pressure; and (ii) symbiont growth may be inhibited or sanctioned by the host at high latitudes. As defensive symbiosis is an important trait in marine habitats, understanding factors that affect the distribution of both the host and symbiont are necessary to fully appreciate the ecological impact of symbiosis.

Extracellular Alkalinization as a Defense Response in Potato Cells.

PubMed

Moroz, Natalia; Fritch, Karen R; Marcec, Matthew J; Tripathi, Diwaker; Smertenko, Andrei; Tanaka, Kiwamu

2017-01-01

A quantitative and robust bioassay to assess plant defense response is important for studies of disease resistance and also for the early identification of disease during pre- or non-symptomatic phases. An increase in extracellular pH is known to be an early defense response in plants. In this study, we demonstrate extracellular alkalinization as a defense response in potatoes. Using potato suspension cell cultures, we observed an alkalinization response against various pathogen- and plant-derived elicitors in a dose- and time-dependent manner. We also assessed the defense response against a variety of potato pathogens, such as protists ( Phytophthora infestans and Spongospora subterranea ) and fungi ( Verticillium dahliae and Colletotrichum coccodes ). Our results show that extracellular pH increases within 30 min in proportion to the number of pathogen spores added. Consistently with the alkalinization effect, the higher transcription level of several defense-related genes and production of reactive oxygen species was observed. Our results demonstrate that the alkalinization response is an effective marker to study early stages of defense response in potatoes.

Analysis of piRNA-mediated silencing of active TEs in Drosophila melanogaster suggests limits on the evolution of host genome defense.

PubMed

Kelleher, Erin S; Barbash, Daniel A

2013-08-01

The Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of transposable element (TE) infection by imposing small-RNA-mediated silencing. Because silencing is targeted by TE-derived piRNAs, piRNA production is posited to be central to the evolution of genome defense. We harnessed genomic data sets from Drosophila melanogaster, including genome-wide measures of piRNA, mRNA, and genomic abundance, along with estimates of age structure and risk of ectopic recombination, to address fundamental questions about the functional and evolutionary relationships between TE families and their regulatory piRNAs. We demonstrate that mRNA transcript abundance, robustness of "ping-pong" amplification, and representation in piRNA clusters together explain the majority of variation in piRNA abundance between TE families, providing the first robust statistical support for the prevailing model of piRNA biogenesis. Intriguingly, we also discover that the most transpositionally active TE families, with the greatest capacity to induce harmful mutations or disrupt gametogenesis, are not necessarily the most abundant among piRNAs. Rather, the level of piRNA targeting is largely independent of recent transposition rate for active TE families, but is rapidly lost for inactive TEs. These observations are consistent with population genetic theory that suggests a limited selective advantage for host repression of transposition. Additionally, we find no evidence that piRNA targeting responds to selection against a second major cost of TE infection: ectopic recombination between TE insertions. Our observations confirm the pivotal role of piRNA-mediated silencing in defending the genome against selfish transposition, yet also suggest limits to the optimization of host genome defense.

Behavioral Strategies of Phorid Parasitoids and Responses of Their Hosts, the Leaf-Cutting Ants

PubMed Central

Elizalde, Luciana; Folgarait, Patricia Julia

2012-01-01

Host-searching and oviposition behaviors of parasitoids, and defensive responses of the hosts, are fundamental in shaping the ecology of host-parasitoid interactions. In order to uncover key behavioral features for the little known interactions between phorid parasitoids (Diptera: Phoridae) and their leaf-cutting ant hosts (Formicidae: Attini), host-related behavioral strategies (i.e., host searching and oviposition) for 13 phorid species, and host defensive responses (i.e., hitchhikers and particular body postures) for 11 ant species, were studied. Data was collected at 14 localities, one of them characterized by its high species richness for this host-parasitoid system. Phorid species showed both great variation and specificity in attacking behaviors. Some chose their hosts using either an ambush or an actively searching strategy, while some species attacked ants on different body parts, and specialized on ants performing different tasks, such as when ants were foraging, removing wastes to refuse piles, or repairing the nest. Combining all the behaviors recorded, most phorid species differed in performance in at least one, making it possible to recognize species in the field through their behavior. Phorid species that attacked hosts with greater activity levels showed overall higher attack rates, although there was no significant correlation between attack rates by most phorid species and ant activity outside the nest while parasitoids were attacking. The presence of phorids was a significant determinant for the presence of defensive behaviors by the ants. Although ant species varied in the incidence levels of these defensive behaviors, most ant species reacted against different phorids by utilizing similar behaviors, in contrast to what parasitoids do. General features of the observed phorid-ant interactions were parasitoid specialization and corresponding high interspecific variation in their behaviors, while their hosts showed generalized responses to attacks

Anatomy and Physiology of the Urinary Tract: Relation to Host Defense and Microbial Infection

PubMed Central

HICKLING, DUANE R.; SUN, TUNG-TIEN; WU, XUE-RU

2015-01-01

The urinary tract exits to a body surface area that is densely populated by a wide range of microbes. Yet, under most normal circumstances, it is typically considered sterile, i.e., devoid of microbes, a stark contrast to the gastrointestinal and upper respiratory tracts where many commensal and pathogenic microbes call home. Not surprisingly, infection of the urinary tract over a healthy person’s lifetime is relatively infrequent, occurring once or twice or not at all for most people. For those who do experience an initial infection, the great majority (70% to 80%) thankfully do not go on to suffer from multiple episodes. This is a far cry from the upper respiratory tract infections, which can afflict an otherwise healthy individual countless times. The fact that urinary tract infections are hard to elicit in experimental animals except with inoculum 3–5 orders of magnitude greater than the colony counts that define an acute urinary infection in humans (105 cfu/ml), also speaks to the robustness of the urinary tract defense. How can the urinary tract be so effective in fending off harmful microbes despite its orifice in a close vicinity to that of the microbe-laden gastrointestinal tract? While a complete picture is still evolving, the general consensus is that the anatomical and physiological integrity of the urinary tract is of paramount importance in maintaining a healthy urinary tract. When this integrity is breached, however, the urinary tract can be at a heightened risk or even recurrent episodes of microbial infections. In fact, recurrent urinary tract infections are a significant cause of morbidity and time lost from work and a major challenge to manage clinically. Additionally, infections of the upper urinary tract often require hospitalization and prolonged antibiotic therapy. In this chapter, we provide an overview of the basic anatomy and physiology of the urinary tract with an emphasis on their specific roles in host defense. We also highlight the

Anatomy and Physiology of the Urinary Tract: Relation to Host Defense and Microbial Infection.

PubMed

Hickling, Duane R; Sun, Tung-Tien; Wu, Xue-Ru

2015-08-01

The urinary tract exits to a body surface area that is densely populated by a wide range of microbes. Yet, under most normal circumstances, it is typically considered sterile, i.e., devoid of microbes, a stark contrast to the gastrointestinal and upper respiratory tracts where many commensal and pathogenic microbes call home. Not surprisingly, infection of the urinary tract over a healthy person's lifetime is relatively infrequent, occurring once or twice or not at all for most people. For those who do experience an initial infection, the great majority (70% to 80%) thankfully do not go on to suffer from multiple episodes. This is a far cry from the upper respiratory tract infections, which can afflict an otherwise healthy individual countless times. The fact that urinary tract infections are hard to elicit in experimental animals except with inoculum 3-5 orders of magnitude greater than the colony counts that define an acute urinary infection in humans (105 cfu/ml), also speaks to the robustness of the urinary tract defense. How can the urinary tract be so effective in fending off harmful microbes despite its orifice in a close vicinity to that of the microbe-laden gastrointestinal tract? While a complete picture is still evolving, the general consensus is that the anatomical and physiological integrity of the urinary tract is of paramount importance in maintaining a healthy urinary tract. When this integrity is breached, however, the urinary tract can be at a heightened risk or even recurrent episodes of microbial infections. In fact, recurrent urinary tract infections are a significant cause of morbidity and time lost from work and a major challenge to manage clinically. Additionally, infections of the upper urinary tract often require hospitalization and prolonged antibiotic therapy. In this chapter, we provide an overview of the basic anatomy and physiology of the urinary tract with an emphasis on their specific roles in host defense. We also highlight the

Host-imposed manganese starvation of invading pathogens: two routes to the same destination

PubMed Central

Morey, Jacqueline R.; McDevitt, Christopher A.; Kehl-Fie, Thomas E.

2015-01-01

During infection invading pathogens must acquire all essential nutrients, including first row transition metals, from the host. To combat invaders, the host exploits this fact and restricts the availability of these nutrients using a defense mechanism known as nutritional immunity. While iron sequestration is the most well-known aspect of this defense, recent work has revealed that the host restricts the availability of other essential elements, notably manganese, during infection. Furthermore, these studies have revealed that the host utilizes multiple strategies that extend beyond metal sequestration to prevent bacteria from obtaining these metals. This review will discuss the mechanisms by which bacteria attempt to obtain the essential first row transition metal ion manganese during infection, and the approaches utilized by the host to prevent this occurrence. In addition, this review will discuss the impact of host-imposed manganese starvation on invading bacteria. PMID:25836716

Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens

PubMed Central

Randow, Felix; MacMicking, John D.; James, Leo C.

2013-01-01

Our prevailing view of vertebrate host defense is strongly shaped by the notion of a specialized set of immune cells as sole guardians of antimicrobial resistance. Yet this view greatly underestimates a capacity for most cell lineages—the majority of which fall outside the traditional province of the immune system—to defend themselves against infection. This ancient and ubiquitous form of host protection is termed cell-autonomous immunity and operates across all three domains of life. Here, we discuss the organizing principles that govern cellular self-defense and how intracellular compartmentalization has shaped its activities to provide effective protection against a wide variety of microbial pathogens. PMID:23661752

Cellular self-defense: how cell-autonomous immunity protects against pathogens.

PubMed

Randow, Felix; MacMicking, John D; James, Leo C

2013-05-10

Our prevailing view of vertebrate host defense is strongly shaped by the notion of a specialized set of immune cells as sole guardians of antimicrobial resistance. Yet this view greatly underestimates a capacity for most cell lineages-the majority of which fall outside the traditional province of the immune system-to defend themselves against infection. This ancient and ubiquitous form of host protection is termed cell-autonomous immunity and operates across all three domains of life. Here, we discuss the organizing principles that govern cellular self-defense and how intracellular compartmentalization has shaped its activities to provide effective protection against a wide variety of microbial pathogens.

Comparative Genomics and Host Resistance against Infectious Diseases

PubMed Central

Qureshi, Salman T.; Skamene, Emil

1999-01-01

The large size and complexity of the human genome have limited the identification and functional characterization of components of the innate immune system that play a critical role in front-line defense against invading microorganisms. However, advances in genome analysis (including the development of comprehensive sets of informative genetic markers, improved physical mapping methods, and novel techniques for transcript identification) have reduced the obstacles to discovery of novel host resistance genes. Study of the genomic organization and content of widely divergent vertebrate species has shown a remarkable degree of evolutionary conservation and enables meaningful cross-species comparison and analysis of newly discovered genes. Application of comparative genomics to host resistance will rapidly expand our understanding of human immune defense by facilitating the translation of knowledge acquired through the study of model organisms. We review the rationale and resources for comparative genomic analysis and describe three examples of host resistance genes successfully identified by this approach. PMID:10081670

Overseas Military Bases: Understanding Host Nation Support

DTIC Science & Technology

2012-02-15

and do not reflect the official policy or position of the United States government or the Department of Defense. In accordance with Air Force...Instruction 51-303, it is not copyrighted, but is the property of the US government . Biography Commander Jeffrey J. Draeger, an Ohio native...hosting decisions, this study seeks greater awareness of the determinants of host nation hospitality. By examining overseas bases in Ecuador and

Plasmacytoid Dendritic Cells Promote Host Defense Against Acute Pneumovirus Infection via the TLR7-MyD88-Dependent Signaling Pathway

PubMed Central

Davidson, Sophia; Kaiko, Gerard; Loh, Zhixuan; Lalwani, Amit; Zhang, Vivian; Spann, Kirsten; Foo, Shen Yun; Hansbro, Nicole; Uematsu, Satoshi; Akira, Shizuo; Matthaei, Klaus I.; Rosenberg, Helene F.; Foster, Paul S.; Phipps, Simon

2012-01-01

Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants. In human infants, plasmacytoid dendritic cells (pDC) are recruited to the nasal compartment during infection and initiate host defense through the secretion of type I IFN, IL-12 and IL-6. However, RSV-infected pDCs are refractory to TLR7-mediated activation. Here, we used the rodent-specific pathogen, pneumonia virus of mice (PVM), to determine the contribution of pDC and TLR7-signaling to the development of the innate inflammatory and early adaptive immune response. In wild-type (WT) but not TLR7- or myeloid differentiation protein 88 (MyD88)-deficient mice, PVM inoculation led to a marked infiltration of pDCs and increased expression of type I, II and III IFNs. The delayed induction of IFNs in the absence of TLR7 or MyD88 was associated with a diminished innate inflammatory response and augmented virus recovery from lung tissue. In the absence of TLR7, PVM-specific CD8+ T cell cytokine production was abrogated. The adoptive transfer of TLR7-sufficient but not TLR7-deficient pDC to TLR7-gene-deleted mice recapitulated the antiviral responses observed in WT mice and promoted virus clearance. In summary, TLR7-mediated signaling by pDC is required for appropriate innate responses to acute pneumovirus infection. It is conceivable that as-yet-unidentified defects in the TLR7 signaling pathway may be associated with elevated levels of RSV-associated morbidity and mortality among otherwise healthy human infants. PMID:21482736

Does chemical aposematic (warning) signaling occur between host plants and their potential parasitic plants?

PubMed

Lev-Yadun, Simcha

2013-07-01

Aposematism (warning) signaling is a common defensive mechanism toward predatory or herbivorous animals, i.e., interactions between different trophic levels. I propose that it should be considered at least as a working hypothesis that chemical aposematism operates between certain host plants and their plant predators, parasitic plants, and that although they are also plants, they belong to a higher trophic level. Specific host plant genotypes emit known repelling chemical signals toward parasitic plants, which reduce the level of, slow the directional parasite growth (attack) toward the signaling hosts, or even cause parasitic plants to grow away from them in response to these chemicals. Chemical host aposematism toward parasitic plants may be a common but overlooked defense from parasitic plants.

Host plant-specific remodeling of midgut physiology in the generalist insect herbivore Trichoplusia ni.

PubMed

Herde, Marco; Howe, Gregg A

2014-07-01

Species diversity in terrestrial ecosystems is influenced by plant defense compounds that alter the behavior, physiology, and host preference of insect herbivores. Although it is established that insects evolved the ability to detoxify specific allelochemicals, the mechanisms by which polyphagous insects cope with toxic compounds in diverse host plants are not well understood. Here, we used defended and non-defended plant genotypes to study how variation in chemical defense affects midgut responses of the lepidopteran herbivore Trichoplusia ni, which is a pest of a wide variety of native and cultivated plants. The genome-wide midgut transcriptional response of T. ni larvae to glucosinolate-based defenses in the crucifer Arabidopsis thaliana was characterized by strong induction of genes encoding Phase I and II detoxification enzymes. In contrast, the response of T. ni to proteinase inhibitors and other jasmonate-regulated defenses in tomato (Solanum lycopersicum) was dominated by changes in the expression of digestive enzymes and, strikingly, concomitant repression of transcripts encoding detoxification enzymes. Unbiased proteomic analyses of T. ni feces demonstrated that tomato defenses remodel the complement of T.ni digestive enzymes, which was associated with increased amounts of serine proteases and decreased lipase protein abundance upon encountering tomato defense chemistry. These collective results indicate that T. ni adjusts its gut physiology to the presence of host plant-specific chemical defenses, and further suggest that plants may exploit this digestive flexibility as a defensive strategy to suppress the production of enzymes that detoxify allelochemicals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Alterations in the host defense properties of human milk following prolonged storage or pasteurization.

PubMed

Akinbi, Henry; Meinzen-Derr, Jareen; Auer, Christine; Ma, Yan; Pullum, Derek; Kusano, Ryosuke; Reszka, Krzysztof J; Zimmerly, Kira

2010-09-01

Preterm infants are often fed pasteurized donor milk or mother's milk that has been stored frozen for up to 4 weeks. Our objectives were to assess the impact of pasteurization or prolonged storage at -20 degrees C on the immunologic components of human milk and the capability of the different forms of human milk to support bacterial proliferation. The concentrations and activities of major host defense proteins in the whey fractions of mother's milk stored for 4 weeks at -20 degrees C or pasteurized human donor milk were compared with freshly expressed human milk. Proliferation of bacteria incubated in the 3 forms of human milk was assessed. Relative to freshly expressed human milk, the concentrations of lysozyme, lactoferrin, lactoperoxidase, and secretory immunoglobulin A were reduced 50% to 82% in pasteurized donor milk and the activities of lysozyme and lactoperoxidase were 74% to 88% lower (P < 0.01). Proliferation of bacterial pathogens in pasteurized donor milk was enhanced 1.8- to 4.6-fold compared with fresh or frozen human milk (P < 0.01). The immunomodulatory proteins in human milk are reduced by pasteurization and, to a lesser extent, by frozen storage, resulting in decreased antibacterial capability. Stringent procedure to minimize bacterial contamination is essential during handling of pasteurized milk.

Early host response in the mammary gland after experimental Streptococcus uberis challenge in heifers.

PubMed

de Greeff, Astrid; Zadoks, Ruth; Ruuls, Lisette; Toussaint, Mathilda; Nguyen, Thi Kim Anh; Downing, Alison; Rebel, Johanna; Stockhofe-Zurwieden, Norbert; Smith, Hilde

2013-06-01

Streptococcus uberis is a highly prevalent causative agent of bovine mastitis, which leads to large economic losses in the dairy industry. The aim of this study was to examine the host response during acute inflammation after experimental challenge with capsulated Strep. uberis. Gene expression in response to Strep. uberis was compared between infected and control quarters in 3 animals. All quarters (n=16) were sampled at 16 different locations. Microarray data showed that 239 genes were differentially expressed between infected and control quarters. No differences in gene expression were observed between the different locations. Microarray data were confirmed for several genes using quantitative PCR analysis. Genes differentially expressed due to early Strep. uberis mastitis represented several stages of the process of infection: (1) pathogen recognition; (2) chemoattraction of neutrophils; (3) tissue repair mechanisms; and (4) bactericidal activity. Three different pathogen recognition genes were induced: ficolins, lipopolysaccharide binding protein, and toll-like receptor 2. Calgranulins were found to be the most strongly upregulated genes during early inflammation. By histology and immunohistochemistry, we demonstrated that changes in gene expression in response to Strep. uberis were induced both in infiltrating somatic milk cells and in mammary epithelial cells, demonstrating that the latter cell type plays a role in milk production as well as immune responsiveness. Given the rapid development of inflammation or mastitis after infection, early diagnosis of (Strep. uberis) mastitis is required for prevention of disease and spread of the pathogen. Insight into host responses could help to design immunomodulatory therapies to dampen inflammation after (early) diagnosis of Strep. uberis mastitis. Future research should focus on development of these early diagnostics and immunomodulatory components for mastitis treatment. Copyright © 2013 American Dairy Science

Insect Outbreaks, Host-Pathogen Interactions, and Induced Plant Defenses

DTIC Science & Technology

2009-09-30

red oaks increases hydrolyzable tannin concentrations20, an induced defense8 that strongly affects average gypsy-moth infection risk in the...laboratory21. Reassuringly, our JA treatment induced hydrolyzable tannins to the same extent as defoliation in nature8 (Table 1, note that control branches...27.05 ± 1.4 Control 23.36 ± 0.9 19.54 ± 0.9 Table 1: Effects of experimental JA spray and natural defoliation on percent hydrolyzable tannin

Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.

PubMed

Reichelt, Mike; Wang, Li; Sommer, Marvin; Perrino, John; Nour, Adel M; Sen, Nandini; Baiker, Armin; Zerboni, Leigh; Arvin, Ann M

2011-02-03

The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant

Analysis of host-pathogen modulators of autophagy during Mycobacterium Tuberculosis infection and therapeutic repercussions.

PubMed

Khan, Arshad; Jagannath, Chinnaswamy

2017-09-03

Mycobacterium tuberculosis is one of the most deadly human pathogens known today in modern world, responsible for about 1.5 million deaths annually. Development of TB disease occurs only in 1 out of 10 individuals exposed to the pathogen which indicates that the competent host defense mechanisms exist in majority of the hosts to control the infection. In the last decade, autophagy has emerged as a key host immune defense mechanism against intracellular M. tuberculosis infection. Autophagy has been demonstrated not only as an effective antimicrobial mechanism for the clearance of M. tuberculosis, but the process has also been suggested to prevent excessive inflammation to avoid the adverse effects of infection on host. Nevertheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to compromise the optimal functioning of host autophagic machinery. This review describes an overview of the various host signaling pathways such as pattern recognition receptors, cytokines, nutrient starvation and other cellular stress that have been implicated in induction of autophagy during M. tuberculosis infection. The review also chalk out the complex interplay of several bacterial factors of M. tuberculosis that are known to be involved in compromising autophagy mediated defense of the host. A comprehensive understanding of the interaction of bacterial and host factors at the intersections of autophagic pathways could provide integrative insights for the development of autophagy-based prophylactics and novel therapeutic interventions for TB.

Involvement of Trichoderma harzianum Epl-1 Protein in the Regulation of Botrytis Virulence- and Tomato Defense-Related Genes.

PubMed

Gomes, Eriston V; Ulhoa, Cirano J; Cardoza, Rosa E; Silva, Roberto N; Gutiérrez, Santiago

2017-01-01

Several Trichoderma spp. are well known for their ability to: (i) act as important biocontrol agents against phytopathogenic fungi; (ii) function as biofertilizers; (iii) increase the tolerance of plants to biotic and abiotic stresses; and (iv) induce plant defense responses via the production and secretion of elicitor molecules. In this study, we analyzed the gene-regulation effects of Trichoderma harzianum Epl-1 protein during the interactions of mutant Δ epl-1 or wild-type T. harzianum strains with: (a) the phytopathogen Botrytis cinerea and (b) with tomato plants, on short (24 h hydroponic cultures) and long periods (4-weeks old plants) after Trichoderma inoculation. Our results indicate that T. harzianum Epl-1 protein affects the in vitro expression of B. cinerea virulence genes, especially those involved in the botrydial biosynthesis ( BcBOT genes), during the mycoparasitism interaction. The tomato defense-related genes were also affected, indicating that Epl-1 is involved in the elicitation of the salicylic acid pathway. Moreover, Epl-1 also regulates the priming effect in host tomato plants and contributes to enhance the interaction with the host tomato plant during the early stage of root colonization.

Involvement of Trichoderma harzianum Epl-1 Protein in the Regulation of Botrytis Virulence- and Tomato Defense-Related Genes

PubMed Central

Gomes, Eriston V.; Ulhoa, Cirano J.; Cardoza, Rosa E.; Silva, Roberto N.; Gutiérrez, Santiago

2017-01-01

Several Trichoderma spp. are well known for their ability to: (i) act as important biocontrol agents against phytopathogenic fungi; (ii) function as biofertilizers; (iii) increase the tolerance of plants to biotic and abiotic stresses; and (iv) induce plant defense responses via the production and secretion of elicitor molecules. In this study, we analyzed the gene-regulation effects of Trichoderma harzianum Epl-1 protein during the interactions of mutant Δepl-1 or wild-type T. harzianum strains with: (a) the phytopathogen Botrytis cinerea and (b) with tomato plants, on short (24 h hydroponic cultures) and long periods (4-weeks old plants) after Trichoderma inoculation. Our results indicate that T. harzianum Epl-1 protein affects the in vitro expression of B. cinerea virulence genes, especially those involved in the botrydial biosynthesis (BcBOT genes), during the mycoparasitism interaction. The tomato defense-related genes were also affected, indicating that Epl-1 is involved in the elicitation of the salicylic acid pathway. Moreover, Epl-1 also regulates the priming effect in host tomato plants and contributes to enhance the interaction with the host tomato plant during the early stage of root colonization. PMID:28611802

Neisseria gonorrhoeae Modulates Iron-Limiting Innate Immune Defenses in Macrophages

PubMed Central

Zughaier, Susu M.; Kandler, Justin L.; Shafer, William M.

2014-01-01

Neisseria gonorrhoeae is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. The gonococcus can survive extracellularly and intracellularly, but in both environments the bacteria must acquire iron from host proteins for survival. However, upon infection the host uses a defensive response by limiting the bioavailability of iron by a number of mechanisms including the enhanced expression of hepcidin, the master iron-regulating hormone, which reduces iron uptake from the gut and retains iron in macrophages. The host also secretes the antibacterial protein NGAL, which sequesters bacterial siderophores and therefore inhibits bacterial growth. To learn whether intracellular gonococci can subvert this defensive response, we examined expression of host genes that encode proteins involved in modulating levels of intracellular iron. We found that N. gonorrhoeae can survive in association (tightly adherent and intracellular) with monocytes and macrophages and upregulates a panel of its iron-responsive genes in this environment. We also found that gonococcal infection of human monocytes or murine macrophages resulted in the upregulation of hepcidin, NGAL, and NRAMP1 as well as downregulation of the expression of the gene encoding the short chain 3-hydroxybutyrate dehydrogenase (BDH2); BDH2 catalyzes the production of the mammalian siderophore 2,5-DHBA involved in chelating and detoxifying iron. Based on these findings, we propose that N. gonorrhoeae can subvert the iron-limiting innate immune defenses to facilitate iron acquisition and intracellular survival. PMID:24489950

Immune Ecosystem of Virus-Infected Host Tissues.

PubMed

Maarouf, Mohamed; Rai, Kul Raj; Goraya, Mohsan Ullah; Chen, Ji-Long

2018-05-06

Virus infected host cells serve as a central immune ecological niche during viral infection and replication and stimulate the host immune response via molecular signaling. The viral infection and multiplication process involves complex intracellular molecular interactions between viral components and the host factors. Various types of host cells are also involved to modulate immune factors in delicate and dynamic equilibrium to maintain a balanced immune ecosystem in an infected host tissue. Antiviral host arsenals are equipped to combat or eliminate viral invasion. However, viruses have evolved with strategies to counter against antiviral immunity or hijack cellular machinery to survive inside host tissue for their multiplication. However, host immune systems have also evolved to neutralize the infection; which, in turn, either clears the virus from the infected host or causes immune-mediated host tissue injury. A complex relationship between viral pathogenesis and host antiviral defense could define the immune ecosystem of virus-infected host tissues. Understanding of the molecular mechanism underlying this ecosystem would uncover strategies to modulate host immune function for antiviral therapeutics. This review presents past and present updates of immune-ecological components of virus infected host tissue and explains how viruses subvert the host immune surveillances.

Structure-activity studies and therapeutic potential of host defense peptides of human thrombin.

PubMed

Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Mörgelin, Matthias; Albiger, Barbara; Malmsten, Martin; Schmidtchen, Artur

2011-06-01

Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

An effector of the Irish potato famine pathogen antagonizes a host autophagy cargo receptor

PubMed Central

Dagdas, Yasin F; Belhaj, Khaoula; Maqbool, Abbas; Chaparro-Garcia, Angela; Pandey, Pooja; Petre, Benjamin; Tabassum, Nadra; Cruz-Mireles, Neftaly; Hughes, Richard K; Sklenar, Jan; Win, Joe; Menke, Frank; Findlay, Kim; Banfield, Mark J; Kamoun, Sophien; Bozkurt, Tolga O

2016-01-01

Plants use autophagy to safeguard against infectious diseases. However, how plant pathogens interfere with autophagy-related processes is unknown. Here, we show that PexRD54, an effector from the Irish potato famine pathogen Phytophthora infestans, binds host autophagy protein ATG8CL to stimulate autophagosome formation. PexRD54 depletes the autophagy cargo receptor Joka2 out of ATG8CL complexes and interferes with Joka2's positive effect on pathogen defense. Thus, a plant pathogen effector has evolved to antagonize a host autophagy cargo receptor to counteract host defenses. DOI: http://dx.doi.org/10.7554/eLife.10856.001 PMID:26765567

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

Plasmodium falciparum erythrocyte membrane protein-1 specifically suppresses early production of host interferon-gamma.

PubMed

D'Ombrain, Marthe C; Voss, Till S; Maier, Alexander G; Pearce, J Andrew; Hansen, Diana S; Cowman, Alan F; Schofield, Louis

2007-08-16

Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) is a variable antigen expressed by P. falciparum, the malarial parasite. PfEMP-1, present on the surface of infected host erythrocytes, mediates erythrocyte binding to vascular endothelium, enabling the parasite to avoid splenic clearance. In addition, PfEMP-1 is proposed to regulate host immune responses via interactions with the CD36 receptor on antigen-presenting cells. We investigated the immunoregulatory function of PfEMP-1 by comparing host cell responses to erythrocytes infected with either wild-type parasites or transgenic parasites lacking PfEMP-1. We showed that PfEMP-1 suppresses the production of the cytokine interferon-gamma by human peripheral blood mononuclear cells early after exposure to P. falciparum. Suppression of this rapid proinflammatory response was CD36 independent and specific to interferon-gamma production by gammadelta-T, NK, and alphabeta-T cells. These data demonstrate a parasite strategy for downregulating the proinflammatory interferon-gamma response and further establish transgenic parasites lacking PfEMP-1 as powerful tools for elucidating PfEMP-1 functions.

Proteomic Characterization of Host Response to Yersinia pestis

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

Chromy, B; Perkins, J; Heidbrink, J

Host-pathogen interactions result in protein expression changes within both the host and the pathogen. Here, results from proteomic characterization of host response following exposure to Yersinia pestis, the causative agent of plague, and to two near neighbors, Y. pseudotuberculosis and Y. enterocolitica, are reported. Human monocyte-like cells were chosen as a model for macrophage immune response to pathogen exposure. Two-dimensional electrophoresis followed by mass spectrometry was used to identify host proteins with differential expression following exposure to these three closely related Yersinia species. This comparative proteomic characterization of host response clearly shows that host protein expression patterns are distinct formore » the different pathogen exposures, and contributes to further understanding of Y. pestis virulence and host defense mechanisms. This work also lays the foundation for future studies aimed at defining biomarkers for presymptomatic detection of plague.« less

Parasitic Cuscuta factor(s) and the detection by tomato initiates plant defense.

PubMed

Fürst, Ursula; Hegenauer, Volker; Kaiser, Bettina; Körner, Max; Welz, Max; Albert, Markus

2016-01-01

Dodders ( Cuscuta spp.) are holoparasitic plants that enwind stems of host plants and penetrate those by haustoria to connect to the vascular bundles. Having a broad host plant spectrum, Cuscuta spp infect nearly all dicot plants - only cultivated tomato as one exception is mounting an active defense specifically against C. reflexa . In a recent work we identified a pattern recognition receptor of tomato, "Cuscuta Receptor 1" (CuRe1), which is critical to detect a "Cuscuta factor" (CuF) and initiate defense responses such as the production of ethylene or the generation of reactive oxygen species. CuRe1 also contributes to the tomato resistance against C. reflexa . Here we point to the fact that CuRe1 is not the only relevant component for full tomato resistance but it requires additional defense mechanisms, or receptors, respectively, to totally fend off the parasite.

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.

Water-deficit and fungal infection can differentially affect the production of different classes of defense compounds in two host pines of mountain pine beetle.

PubMed

Erbilgin, Nadir; Cale, Jonathan A; Lusebrink, Inka; Najar, Ahmed; Klutsch, Jennifer G; Sherwood, Patrick; Enrico Bonello, Pierluigi; Evenden, Maya L

2017-03-01

Bark beetles are important agents of tree mortality in conifer forests and their interaction with trees is influenced by host defense chemicals, such as monoterpenes and phenolics. Since mountain pine beetle (Dendroctonus ponderosae Hopkins) has expanded its host range from lodgepole pine (Pinus contorta Doug. ex Loud. (var. latifolia Engelm.))-dominated forests to the novel jack pine (Pinus banksiana Lamb.) forests in western Canada, studies investigating the jack pine suitability as a host for this beetle have exclusively focused on monoterpenes, and whether phenolics affect jack pine suitability to mountain pine beetle and its symbiotic fungus Grosmannia clavigera is unknown. We investigated the phenolic and monoterpene composition in phloem and foliage of jack and lodgepole pines, and their subsequent change in response to water deficit and G. clavigera inoculation treatments. In lodgepole pine phloem, water deficit treatment inhibited the accumulation of both the total and richness of phenolics, but had no effect on total monoterpene production or richness. Fungal infection also inhibited the total phenolic production and had no effect on phenolic or monoterpene richness, but increased total monoterpene synthesis by 71%. In jack pine phloem, water deficit treatment reduced phenolic production, but had no effect on phenolic or monoterpene richness or total monoterpenes. Fungal infection did not affect phenolic or monoterpene production. Lesions of both species contained lower phenolics but higher monoterpenes than non-infected phloem in the same tree. In both species, richness of monoterpenes and phenolics was greater in non-infected phloem than in lesions. We conclude that monoterpenes seem to be a critical component of induced defenses against G. clavigera in both jack and lodgepole pines; however, a lack of increased monoterpene response to fungal infection is an important evolutionary factor defining jack pine suitability to the mountain pine beetle

The Ustilago maydis Effector Pep1 Suppresses Plant Immunity by Inhibition of Host Peroxidase Activity

PubMed Central

Zechmann, Bernd; Hillmer, Morten; Doehlemann, Gunther

2012-01-01

The corn smut Ustilago maydis establishes a biotrophic interaction with its host plant maize. This interaction requires efficient suppression of plant immune responses, which is attributed to secreted effector proteins. Previously we identified Pep1 (Protein essential during penetration-1) as a secreted effector with an essential role for U. maydis virulence. pep1 deletion mutants induce strong defense responses leading to an early block in pathogenic development of the fungus. Using cytological and functional assays we show that Pep1 functions as an inhibitor of plant peroxidases. At sites of Δpep1 mutant penetrations, H2O2 strongly accumulated in the cell walls, coinciding with a transcriptional induction of the secreted maize peroxidase POX12. Pep1 protein effectively inhibited the peroxidase driven oxidative burst and thereby suppresses the early immune responses of maize. Moreover, Pep1 directly inhibits peroxidases in vitro in a concentration-dependent manner. Using fluorescence complementation assays, we observed a direct interaction of Pep1 and the maize peroxidase POX12 in vivo. Functional relevance of this interaction was demonstrated by partial complementation of the Δpep1 mutant defect by virus induced gene silencing of maize POX12. We conclude that Pep1 acts as a potent suppressor of early plant defenses by inhibition of peroxidase activity. Thus, it represents a novel strategy for establishing a biotrophic interaction. PMID:22589719

Indirect plant defense against insect herbivores: a review.

PubMed

Aljbory, Zainab; Chen, Ming-Shun

2018-02-01

Plants respond to herbivore attack by launching 2 types of defenses: direct defense and indirect defense. Direct defense includes all plant traits that increase the resistance of host plants to insect herbivores by affecting the physiology and/or behavior of the attackers. Indirect defense includes all traits that by themselves do not have significant direct impact on the attacking herbivores, but can attract natural enemies of the herbivores and thus reduce plant loss. When plants recognize herbivore-associated elicitors, they produce and release a blend of volatiles that can attract predators, parasites, and other natural enemies. Known herbivore-associated elicitors include fatty acid-amino acid conjugates, sulfur-containing fatty acids, fragments of cell walls, peptides, esters, and enzymes. Identified plant volatiles include terpenes, nitrogenous compounds, and indoles. In addition, constitive traits including extrafloral nectars, food bodies, and domatia can be further induced to higher levels and attract natural enemies as well as provide food and shelter to carnivores. A better understanding of indirect plant defense at global and componential levels via advanced high throughput technologies may lead to utilization of indirect defense in suppression of herbivore damage to plants. © 2016 Institute of Zoology, Chinese Academy of Sciences.

Burn wound sepsis may be promoted by a failure of local antibacterial host defenses.

PubMed Central

Deitch, E A; Bridges, R M; Dobke, M; McDonald, J C

1987-01-01

Little attention has been focused on the local burn wound environment, even though burn wound sepsis is a common cause of death in the burn victim. To characterize the effect of the local burn wound environment on neutrophil function and metabolism, the opsonic activity of blister fluid specimens against Pseudomonas aeruginosa was measured as was the effect of blister fluid on control neutrophil oxygen consumption using preopsonized zymosan and f-met-leu-phe (FMLP) as stimuli. Blister fluid did not support the killing of P. aeruginosa by normal neutrophils as well as normal serum. Additionally, blister fluid inhibited zymosan-stimulated, but not FMLP-stimulated, neutrophil oxygen consumption. The inhibitory effect of blister fluid on zymosan-stimulated oxygen consumption correlated with the extent of complement activation, measured as C3d or C3AI (p less than 0.01). That blister fluid did not inhibit the FMLP-mediated respiratory burst supports the concept that the blister fluid inhibitory effect on the zymosan-mediated respiratory burst was mediated through the complement receptor. These findings that blister fluid can affect the bactericidal and metabolic activity of normal neutrophils support the concept that cellular function can be altered by the microenvironment in which the cells are bathed. This potential impairment of host defenses within the burn wound could predispose the burn victim to burn wound sepsis. PMID:3115207

A Novel Role for Pro-Coagulant Microvesicles in the Early Host Defense against Streptococcus pyogenes

PubMed Central

Oehmcke, Sonja; Westman, Johannes; Malmström, Johan; Mörgelin, Matthias; Olin, Anders I.; Kreikemeyer, Bernd; Herwald, Heiko

2013-01-01

Previous studies have shown that stimulation of whole blood or peripheral blood mononuclear cells with bacterial virulence factors results in the sequestration of pro-coagulant microvesicles (MVs). These particles explore their clotting activity via the extrinsic and intrinsic pathway of coagulation; however, their pathophysiological role in infectious diseases remains enigmatic. Here we describe that the interaction of pro-coagulant MVs with bacteria of the species Streptococcus pyogenes is part of the early immune response to the invading pathogen. As shown by negative staining electron microscopy and clotting assays, pro-coagulant MVs bind in the presence of plasma to the bacterial surface. Fibrinogen was identified as a linker that, through binding to the M1 protein of S. pyogenes, allows the opsonization of the bacteria by MVs. Surface plasmon resonance analysis revealed a strong interaction between pro-coagulant MVs and fibrinogen with a KD value in the nanomolar range. When performing a mass-spectrometry-based strategy to determine the protein quantity, a significant up-regulation of the fibrinogen-binding integrins CD18 and CD11b on pro-coagulant MVs was recorded. Finally we show that plasma clots induced by pro-coagulant MVs are able to prevent bacterial dissemination and possess antimicrobial activity. These findings were confirmed by in vivo experiments, as local treatment with pro-coagulant MVs dampens bacterial spreading to other organs and improved survival in an invasive streptococcal mouse model of infection. Taken together, our data implicate that pro-coagulant MVs play an important role in the early response of the innate immune system in infectious diseases. PMID:23935504

Colonization behaviors of mountain pine beetle on novel hosts: Implications for range expansion into northeastern North America

PubMed Central

Venette, Robert C.; Maddox, Mitchell P.; Aukema, Brian H.

2017-01-01

As climates change, thermal limits may no longer constrain some native herbivores within their historical ranges. The mountain pine beetle, Dendroctonus ponderosae Hopkins, is a tree-killing bark beetle native to western North America that is currently expanding its range. Continued eastward expansion through the newly invaded and novel jack pine (Pinus banksiana Lamb.) trees of the Canadian boreal forest could result in exposure of several species of novel potential host pines common in northeastern North America to this oligophagous herbivore. Due to the tightly co-evolved relationship between mountain pine beetle and western pine hosts, in which the insect utilizes the defensive chemistry of the host to stimulate mass attacks, we hypothesized that lack of co-evolutionary association would affect the host attraction and acceptance behaviors of this insect among novel hosts, particularly those with little known historical association with an aggressive stem-infesting insect. We studied how beetle behavior differed among the various stages of colonization on newly cut logs of four novel potential pine host species; jack, red (P. resinosa Ait.), eastern white (P. strobus L.) and Scots (P. sylvestris L.) pines, as well as two historical hosts, ponderosa (P. ponderosa Dougl. ex. Laws. var. scopulorum Engelm.) and lodgepole (P. contorta Dougl. var. latifolia Engelm.) pines. Overall, we found that beetle colonization behaviors at each stage in the colonization process differ between pine hosts, likely due to differing chemical and physical bark traits. Pines without co-evolved constitutive defenses against mountain pine beetle exhibited reduced amounts of defensive monoterpenoid chemicals; however, such patterns also reduced beetle attraction and colonization. Neither chemical nor physical defenses fully defended trees against the various stages of host procurement that can result in tree colonization and death. PMID:28472047

Colonization behaviors of mountain pine beetle on novel hosts: Implications for range expansion into northeastern North America.

PubMed

Rosenberger, Derek W; Venette, Robert C; Maddox, Mitchell P; Aukema, Brian H

2017-01-01

As climates change, thermal limits may no longer constrain some native herbivores within their historical ranges. The mountain pine beetle, Dendroctonus ponderosae Hopkins, is a tree-killing bark beetle native to western North America that is currently expanding its range. Continued eastward expansion through the newly invaded and novel jack pine (Pinus banksiana Lamb.) trees of the Canadian boreal forest could result in exposure of several species of novel potential host pines common in northeastern North America to this oligophagous herbivore. Due to the tightly co-evolved relationship between mountain pine beetle and western pine hosts, in which the insect utilizes the defensive chemistry of the host to stimulate mass attacks, we hypothesized that lack of co-evolutionary association would affect the host attraction and acceptance behaviors of this insect among novel hosts, particularly those with little known historical association with an aggressive stem-infesting insect. We studied how beetle behavior differed among the various stages of colonization on newly cut logs of four novel potential pine host species; jack, red (P. resinosa Ait.), eastern white (P. strobus L.) and Scots (P. sylvestris L.) pines, as well as two historical hosts, ponderosa (P. ponderosa Dougl. ex. Laws. var. scopulorum Engelm.) and lodgepole (P. contorta Dougl. var. latifolia Engelm.) pines. Overall, we found that beetle colonization behaviors at each stage in the colonization process differ between pine hosts, likely due to differing chemical and physical bark traits. Pines without co-evolved constitutive defenses against mountain pine beetle exhibited reduced amounts of defensive monoterpenoid chemicals; however, such patterns also reduced beetle attraction and colonization. Neither chemical nor physical defenses fully defended trees against the various stages of host procurement that can result in tree colonization and death.

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

Host-defense and trefoil factor family peptides in skin secretions of the Mawa clawed frog Xenopus boumbaensis (Pipidae).

PubMed

Conlon, J Michael; Mechkarska, Milena; Kolodziejek, Jolanta; Leprince, Jérôme; Coquet, Laurent; Jouenne, Thierry; Vaudry, Hubert; Nowotny, Norbert; King, Jay D

2015-10-01

Peptidomic analysis of norepinephrine-stimulated skin secretions from the octoploid Mawa clawed frog Xenopus boumbaensis Loumont, 1983 led to the identification and characterization of 15 host-defense peptides belonging to the magainin (two peptides), peptide glycine-leucine-amide (PGLa; three peptides), xenopsin precursor fragment (XPF; three peptides), caerulein precursor fragment (CPF; two peptides), and caerulein precursor fragment-related peptide (CPF-RP; five peptides) families. In addition, caerulein and three peptides with structural similarity to the trefoil factor family (TFF) peptides, xP2 and xP4 from Xenopus laevis were also present in the secretions. Consistent with data from comparisons of the nucleotides sequence of mitochondrial and nuclear genes, the primary structures of the peptides suggest a close phylogenetic relationship between X. boumbaensis and the octoploid frogs Xenopus amieti and Xenopus andrei. As the three species occupy disjunct ranges within Cameroon, it is suggested that they diverged from a common ancestor by allopatric speciation. Copyright © 2015 Elsevier Inc. All rights reserved.

A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense.

PubMed

Wolf, Dennis; Anto-Michel, Nathaly; Blankenbach, Hermann; Wiedemann, Ansgar; Buscher, Konrad; Hohmann, Jan David; Lim, Bock; Bäuml, Marina; Marki, Alex; Mauler, Maximilian; Duerschmied, Daniel; Fan, Zhichao; Winkels, Holger; Sidler, Daniel; Diehl, Philipp; Zajonc, Dirk M; Hilgendorf, Ingo; Stachon, Peter; Marchini, Timoteo; Willecke, Florian; Schell, Maximilian; Sommer, Björn; von Zur Muhlen, Constantin; Reinöhl, Jochen; Gerhardt, Teresa; Plow, Edward F; Yakubenko, Valentin; Libby, Peter; Bode, Christoph; Ley, Klaus; Peter, Karlheinz; Zirlik, Andreas

2018-02-06

Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo. In contrast, conventional anti-Mac-1 therapy is not specific and blocks a broad repertoire of integrin functionality, inhibits phagocytosis, promotes apoptosis, and fuels a cytokine storm in vivo. Whereas conventional anti-integrin therapy potentiates bacterial sepsis, bacteremia, and mortality, a ligand-specific intervention with anti-M7 is protective. These findings deepen our understanding of ligand-specific integrin functions and open a path for a new field of ligand-targeted anti-integrin therapy to prevent inflammatory conditions.

COMPARISON OF IN VITRO-CULTURED AND WILD-TYPE PERKINSUS MARINUS. II: DOSING METHODS AND HOST RESPONSE

EPA Science Inventory

Endoparasites must breach host barriers to establish infection and then must survive host internal defenses to cause disease. Such barriers may frustrate attempts to experimentally transmit parasites by ?natural' methods. In addition, the host's condition may affect a study's out...

Activity of Potent and Selective Host Defense Peptide Mimetics in Mouse Models of Oral Candidiasis

PubMed Central

Ryan, Lisa K.; Freeman, Katie B.; Masso-Silva, Jorge A.; Falkovsky, Klaudia; Aloyouny, Ashwag; Markowitz, Kenneth; Hise, Amy G.; Fatahzadeh, Mahnaz; Scott, Richard W.

2014-01-01

There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical properties. Here we describe the identification of several HDP mimetics that are broadly active against C. albicans and other species of Candida, rapidly fungicidal, and active against yeast and hyphal cultures and that exhibit low cytotoxicity for mammalian cells. Importantly, specificity for Candida over commensal bacteria was also evident, thereby minimizing potential damage to the endogenous microbiome which otherwise could favor fungal overgrowth. Three compounds were tested as topical agents in two different mouse models of oral candidiasis and were found to be highly active. Following single-dose administrations, total Candida burdens in tongues of infected animals were reduced up to three logs. These studies highlight the potential of HDP mimetics as a new tool in the antifungal arsenal for the treatment of oral candidiasis. PMID:24752272

Evolution of specialization: a phylogenetic study of host range in the red milkweed beetle (Tetraopes tetraophthalmus).

PubMed

Rasmann, Sergio; Agrawal, Anurag A

2011-06-01

Specialization is common in most lineages of insect herbivores, one of the most diverse groups of organisms on earth. To address how and why specialization is maintained over evolutionary time, we hypothesized that plant defense and other ecological attributes of potential host plants would predict the performance of a specialist root-feeding herbivore (the red milkweed beetle, Tetraopes tetraophthalmus). Using a comparative phylogenetic and functional trait approach, we assessed the determinants of insect host range across 18 species of Asclepias. Larval survivorship decreased with increasing phylogenetic distance from the true host, Asclepias syriaca, suggesting that adaptation to plant traits drives specialization. Among several root traits measured, only cardenolides (toxic defense chemicals) correlated with larval survival, and cardenolides also explained the phylogenetic distance effect in phylogenetically controlled multiple regression analyses. Additionally, milkweed species having a known association with other Tetraopes beetles were better hosts than species lacking Tetraopes herbivores, and milkweeds with specific leaf area values (a trait related to leaf function and habitat affiliation) similar to those of A. syriaca were better hosts than species having divergent values. We thus conclude that phylogenetic distance is an integrated measure of phenotypic and ecological attributes of Asclepias species, especially defensive cardenolides, which can be used to explain specialization and constraints on host shifts over evolutionary time.

Altering host resistance to infections through microbial transplantation.

PubMed

Willing, Benjamin P; Vacharaksa, Anjalee; Croxen, Matthew; Thanachayanont, Teerawat; Finlay, B Brett

2011-01-01

Host resistance to bacterial infections is thought to be dictated by host genetic factors. Infections by the natural murine enteric pathogen Citrobacter rodentium (used as a model of human enteropathogenic and enterohaemorrhagic E. coli infections) vary between mice strains, from mild self-resolving colonization in NIH Swiss mice to lethality in C3H/HeJ mice. However, no clear genetic component had been shown to be responsible for the differences observed with C. rodentium infections. Because the intestinal microbiota is important in regulating resistance to infection, and microbial composition is dependent on host genotype, it was tested whether variations in microbial composition between mouse strains contributed to differences in "host" susceptibility by transferring the microbiota of resistant mice to lethally susceptible mice prior to infection. Successful transfer of the microbiota from resistant to susceptible mice resulted in delayed pathogen colonization and mortality. Delayed mortality was associated with increased IL-22 mediated innate defense including antimicrobial peptides Reg3γ and Reg3β, and immunono-neutralization of IL-22 abrogated the beneficial effect of microbiota transfer. Conversely, depletion of the native microbiota in resistant mice by antibiotics and transfer of the susceptible mouse microbiota resulted in reduced innate defenses and greater pathology upon infection. This work demonstrates the importance of the microbiota and how it regulates mucosal immunity, providing an important factor in susceptibility to enteric infection. Transfer of resistance through microbial transplantation (bacteriotherapy) provides additional mechanisms to alter "host" resistance, and a novel means to alter enteric infection and to study host-pathogen interactions.

Parasitic Cuscuta factor(s) and the detection by tomato initiates plant defense

PubMed Central

Fürst, Ursula; Hegenauer, Volker; Kaiser, Bettina; Körner, Max; Welz, Max; Albert, Markus

2016-01-01

ABSTRACT Dodders (Cuscuta spp.) are holoparasitic plants that enwind stems of host plants and penetrate those by haustoria to connect to the vascular bundles. Having a broad host plant spectrum, Cuscuta spp infect nearly all dicot plants – only cultivated tomato as one exception is mounting an active defense specifically against C. reflexa. In a recent work we identified a pattern recognition receptor of tomato, “Cuscuta Receptor 1“ (CuRe1), which is critical to detect a “Cuscuta factor” (CuF) and initiate defense responses such as the production of ethylene or the generation of reactive oxygen species. CuRe1 also contributes to the tomato resistance against C. reflexa. Here we point to the fact that CuRe1 is not the only relevant component for full tomato resistance but it requires additional defense mechanisms, or receptors, respectively, to totally fend off the parasite. PMID:28042379

Turnabout Is Fair Play: Herbivory-Induced Plant Chitinases Excreted in Fall Armyworm Frass Suppress Herbivore Defenses in Maize1[OPEN

PubMed Central

Alves, Patrick C.M.S.; Gaffoor, Iffa; Acevedo, Flor E.; Peiffer, Michelle; Jin, Shan; Han, Yang; Shakeel, Samina; Felton, Gary W.

2016-01-01

The perception of herbivory by plants is known to be triggered by the deposition of insect-derived factors such as saliva and oral secretions, oviposition materials, and even feces. Such insect-derived materials harbor chemical cues that may elicit herbivore and/or pathogen-induced defenses in plants. Several insect-derived molecules that trigger herbivore-induced defenses in plants are known; however, insect-derived molecules suppressing them are largely unknown. In this study, we identified two plant chitinases from fall armyworm (Spodoptera frugiperda) larval frass that suppress herbivore defenses while simultaneously inducing pathogen defenses in maize (Zea mays). Fall armyworm larvae feed in enclosed whorls of maize plants, where frass accumulates over extended periods of time in close proximity to damaged leaf tissue. Our study shows that maize chitinases, Pr4 and Endochitinase A, are induced during herbivory and subsequently deposited on the host with the feces. These plant chitinases mediate the suppression of herbivore-induced defenses, thereby increasing the performance of the insect on the host. Pr4 and Endochitinase A also trigger the antagonistic pathogen defense pathway in maize and suppress fungal pathogen growth on maize leaves. Frass-induced suppression of herbivore defenses by deposition of the plant-derived chitinases Pr4 and Endochitinase A is a unique way an insect can co-opt the plant’s defense proteins for its own benefit. It is also a phenomenon unlike the induction of herbivore defenses by insect oral secretions in most host-herbivore systems. PMID:26979328

Phagocyte dynamics in a highly regenerative urochordate: insights into development and host defense.

PubMed

Lauzon, Robert J; Brown, Christina; Kerr, Louie; Tiozzo, Stefano

2013-02-15

Phagocytosis is a cellular process by which particles and foreign bodies are engulfed and degraded by specialized cells. It is functionally involved in nutrient acquisition and represents a fundamental mechanism used to remove pathogens and cellular debris. In the marine invertebrate chordate Botryllus schlosseri, cell corpse engulfment by phagocytic cells is the recurrent mechanism of programmed cell clearance and a critical process for the successful execution of asexual regeneration and colony homeostasis. In the present study, we have utilized a naturally occurring process of vascular parabiosis coupled with intravascular microinjection of fluorescent bioparticles and liposomes as tools to investigate the dynamics of phagocyte behavior in real-time during cyclical body regeneration. Our findings indicate that B. schlosseri harbors two major populations of post-mitotic phagocytes, which display distinct phagocytic specificity and homing patterns: a static population that lines the circulatory system epithelia, and a mobile population that continuously recirculates throughout the colony and exhibits a characteristic homing pattern within mesenchymal niches called ventral islands (VI). We observed that a significant proportion of ventral island phagocytes (VIP) die and are engulfed by other VIP following takeover. Selective impairment of VIP activity curtailed zooid resorption and asexual development. Together, these findings strongly suggest that ventral islands are sites of phagocyte homing and turnover. As botryllid ascidians represent invertebrate chordates capable of whole body regeneration in a non-embryonic scenario, we discuss the pivotal role that phagocytosis plays in homeostasis, tissue renewal and host defense. Copyright © 2012 Elsevier Inc. All rights reserved.

The Relationship between Host Lifespan and Pathogen Reservoir Potential: An Analysis in the System Arabidopsis thaliana-Cucumber mosaic virus

PubMed Central

Hily, Jean Michel; García, Adrián; Moreno, Arancha; Plaza, María; Wilkinson, Mark D.; Fereres, Alberto; Fraile, Aurora; García-Arenal, Fernando

2014-01-01

Identification of the determinants of pathogen reservoir potential is central to understand disease emergence. It has been proposed that host lifespan is one such determinant: short-lived hosts will invest less in costly defenses against pathogens, so that they will be more susceptible to infection, more competent as sources of infection and/or will sustain larger vector populations, thus being effective reservoirs for the infection of long-lived hosts. This hypothesis is sustained by analyses of different hosts of multihost pathogens, but not of different genotypes of the same host species. Here we examined this hypothesis by comparing two genotypes of the plant Arabidopsis thaliana that differ largely both in life-span and in tolerance to its natural pathogen Cucumber mosaic virus (CMV). Experiments with the aphid vector Myzus persicae showed that both genotypes were similarly competent as sources for virus transmission, but the short-lived genotype was more susceptible to infection and was able to sustain larger vector populations. To explore how differences in defense against CMV and its vector relate to reservoir potential, we developed a model that was run for a set of experimentally-determined parameters, and for a realistic range of host plant and vector population densities. Model simulations showed that the less efficient defenses of the short-lived genotype resulted in higher reservoir potential, which in heterogeneous host populations may be balanced by the longer infectious period of the long-lived genotype. This balance was modulated by the demography of both host and vector populations, and by the genetic composition of the host population. Thus, within-species genetic diversity for lifespan and defenses against pathogens will result in polymorphisms for pathogen reservoir potential, which will condition within-population infection dynamics. These results are relevant for a better understanding of host-pathogen co-evolution, and of the dynamics of

Host Soluble Mediators: Defying the Immunological Inertness of Aspergillus fumigatus Conidia.

PubMed

Wong, Sarah Sze Wah; Aimanianda, Vishukumar

2017-12-24

Aspergillus fumigatus produce airborne spores (conidia), which are inhaled in abundant quantity. In an immunocompromised population, the host immune system fails to clear the inhaled conidia, which then germinate and invade, leading to pulmonary aspergillosis. In an immunocompetent population, the inhaled conidia are efficiently cleared by the host immune system. Soluble mediators of the innate immunity, that involve the complement system, acute-phase proteins, antimicrobial peptides and cytokines, are often considered to play a complementary role in the defense of the fungal pathogen. In fact, the soluble mediators are essential in achieving an efficient clearance of the dormant conidia, which is the morphotype of the fungus upon inhalation by the host. Importantly, harnessing the host soluble mediators challenges the immunological inertness of the dormant conidia due to the presence of the rodlet and melanin layers. In the review, we summarized the major soluble mediators in the lung that are involved in the recognition of the dormant conidia. This knowledge is essential in the complete understanding of the immune defense against A. fumigatus .

Inorganic chemistry of defensive peroxidases in the human oral cavity.

PubMed

Ashby, M T

2008-10-01

The innate host response system is comprised of various mechanisms for orchestrating host response to microbial infection of the oral cavity. The heterogeneity of the oral cavity and the associated microenvironments that are produced give rise to different chemistries that affect the innate defense system. One focus of this review is on how these spatial differences influence the two major defensive peroxidases of the oral cavity, salivary peroxidase (SPO) and myeloperoxidase (MPO). With hydrogen peroxide (H(2)O(2)) as an oxidant, the defensive peroxidases use inorganic ions to produce antimicrobials that are generally more effective than H(2)O(2) itself. The concentrations of the inorganic substrates are different in saliva vs. gingival crevicular fluid (GCF). Thus, in the supragingival regime, SPO and MPO work in unison for the exclusive production of hypothiocyanite (OSCN(-), a reactive inorganic species), which constantly bathes nascent plaques. In contrast, MPO is introduced to the GCF during inflammatory response, and in that environment it is capable of producing hypochlorite (OCl(-)), a chemically more powerful oxidant that is implicated in host tissue damage. A second focus of this review is on inter-person variation that may contribute to different peroxidase function. Many of these differences are attributed to dietary or smoking practices that alter the concentrations of relevant inorganic species in the oral cavity (e.g.: fluoride, F(-); cyanide, CN(-); cyanate, OCN(-); thiocyanate, SCN(-); and nitrate, NO(3)(-)). Because of the complexity of the host and microflora biology and the associated chemistry, it is difficult to establish the significance of the human peroxidase systems during the pathogenesis of oral diseases. The problem is particularly complex with respect to the gingival sulcus and periodontal pockets (where the very different defensive stratagems of GCF and saliva co-mingle). Despite this complexity, intriguing in vitro and in vivo

Using the Defensive Style Questionnaire to evaluate the impact of sex reassignment surgery on defensive mechanisms in transsexual patients.

PubMed

Lobato, Maria Inês; Koff, Walter José; Crestana, Tiago; Chaves, Camila; Salvador, Jaqueline; Petry, Analídia Rodolpho; Silveira, Esalba; Henriques, Alexandre Annes; Cervo, Fábio; Böhme, Eduardo Siam; Massuda, Raffael

2009-12-01

To evaluate the impact of sex reassignment surgery on the defense mechanisms of 32 transsexual patients at two different points in time using the Defensive Style Questionnaire. The Defensive Style Questionnaire was applied to 32 patients upon their admission to the Gender Identity Disorder Program, and 12 months after they had undergone sex reassignment surgery. There were changes in two defense mechanisms: anticipation and idealization. However, no significant differences were observed in terms of the mature, neurotic and immature categories. One possible explanation for this result is the fact that the procedure does not resolve gender dysphoria, which is a core symptom in such patients. Another aspect is related to the early onset of the gender identity disorder, which determines a more regressive defensive structure in these patients. Sex reassignment surgery did not improve the defensive profile as measured by the Defensive Style Questionnaire.

Parasitism by Cuscuta pentagona attenuates host plant defenses against insect herbivores

Treesearch

Justin B. Runyon; Mark C. Mescher; Consuelo M. De Moraes

2008-01-01

Considerable research has examined plant responses to concurrent attack by herbivores and pathogens, but the effects of attack by parasitic plants, another important class of plant-feeding organisms, on plant defenses against other enemies has not been explored. We investigated how attack by the parasitic plant Cuscuta pentagona impacted tomato (

Targeting the host-pathogen interface for treatment of Staphylococcus aureus infection.

PubMed

Park, Bonggoo; Liu, George Y

2012-03-01

Recent emergence of methicillin-resistant Staphylococcus aureus both within and outside healthcare settings has accelerated the use of once reserved last line antibiotics such as vancomycin. With increased use of antibiotics, there has been a rapid rise in the rate of resistance development to the anti-MRSA drugs. As the antibiotic pipeline becomes strained, alternative strategies are being sought for future treatment of S. aureus. Here, we review several novel anti-staphylococcal strategies that, unlike conventional antibiotics, do not target essential gene products elaborated by the pathogen. The approaches seek instead to weaken the S. aureus defense by neutralizing its virulence factors or boosting host immunity. Other strategies target commensal bacteria that naturally colonize the human host to inhibit S. aureus colonization. Ultimately, the aim is to shift the balance between host defense and pathogen virulence in favor of inhibition of S. aureus pathogenic activities.

Identification of genetic loci that contribute to Campylobacter resistance to fowlicidin-1, a chicken host defense peptide

PubMed Central

Hoang, Ky Van; Wang, Ying; Lin, Jun

2012-01-01

Antimicrobial peptides (AMPs) are critical components of host defense limiting bacterial infections at the gastrointestinal mucosal surface. Bacterial pathogens have co-evolved with host innate immunity and developed means to counteract the effect of endogenous AMPs. However, molecular mechanisms of AMP resistance in Campylobacter, an important human food-borne pathogen with poultry as a major reservoir, are still largely unknown. In this study, random transposon mutagenesis and targeted site-directed mutagenesis approaches were used to identify genetic loci contributing Campylobacter resistance to fowlicidin-1, a chicken AMP belonging to cathelicidin family. An efficient transposon mutagenesis approach (EZ::TN™ Transposome) in conjunction with a microtiter plate screening identified three mutants whose susceptibilities to fowlicidin-1 were significantly increased. Backcrossing of the transposon mutations into parent strain confirmed that the AMP-sensitive phenotype in each mutant was linked to the specific transposon insertion. Direct sequencing showed that these mutants have transposon inserted in the genes encoding two-component regulator CbrR, transporter CjaB, and putative trigger factor Tig. Genomic analysis also revealed an operon (Cj1580c-1584c) that is homologous to sapABCDF, an operon conferring resistance to AMP in other pathogens. Insertional inactivation of Cj1583c (sapB) significantly increased susceptibility of Campylobacter to fowlicidin-1. The sapB as well as tig and cjaB mutants were significantly impaired in their ability to compete with their wild-type strain 81–176 to colonize the chicken cecum. Together, this study identified four genetic loci in Campylobacter that will be useful for characterizing molecular basis of Campylobacter resistance to AMPs, a significant knowledge gap in Campylobacter pathogenesis. PMID:22919624

Symptomless endophytic fungi suppress endogenous levels of salicylic acid and interact with the jasmonate-dependent indirect defense traits of their host, lima bean (Phaseolus lunatus).

PubMed

Navarro-Meléndez, Ariana L; Heil, Martin

2014-07-01

Symptomless ‘type II’ fungal endophytes colonize their plant host horizontally and exert diverse effects on its resistance phenotype. Here, we used wild Lima bean (Phaseolus lunatus) plants that were experimentally colonized with one of three strains of natural endophytes (Bartalinia pondoensis, Fusarium sp., or Cochliobolus lunatus) to investigate the effects of fungal colonization on the endogenous levels of salicylic acid (SA) and jasmonic acid (JA) and on two JA-dependent indirect defense traits. Colonization with Fusarium sp. enhanced JA levels in intact leaves, whereas B. pondoensis suppressed the induction of endogenous JA in mechanically damaged leaves. Endogenous SA levels in intact leaves were significantly decreased by all strains and B. pondoensis and Fusarium sp. decreased SA levels after mechanical damage. Colonization with Fusarium sp. or C. lunatus enhanced the number of detectable volatile organic compounds (VOCs) emitted from intact leaves, and all three strains enhanced the relative amount of several VOCs emitted from intact leaves as well as the number of detectable VOCs emitted from slightly damaged leaves. All three strains completely suppressed the induced secretion of extrafloral nectar (EFN) after the exogenous application of JA. Symptomless endophytes interact in complex and strain-specific ways with the endogenous levels of SA and JA and with the defense traits that are controlled by these hormones. These interactions can occur both upstream and downstream of the defense hormones.

Characterizing the early life history of an imperiled freshwater mussel (Ptychobranchus jonesi) with host-fish determination and fecundity estimation

USGS Publications Warehouse

Mcleod, John; Jelks, Howard L.; Pursifull, Sandra; Johnson, Nathan A.

2017-01-01

Conservation of imperiled species is frequently challenged by insufficient knowledge of life history and environmental factors that affect various life stages. The larvae (glochidia) of most freshwater mussels in the family Unionidae are obligate ectoparasites of fishes. We described the early life history of the federally endangered Southern Kidneyshell Ptychobranchus jonesi and compared methods for estimating fecundity and conducting host trials on this conglutinate-producing mussel species. Glochidial inoculation baths and direct feeding of conglutinates to Percina nigrofasciata, Etheostoma edwini, and Etheostoma fusiforme resulted in successful metamorphosis to the juvenile life stage. Ptychobranchus jonesi glochidia did not metamorphose on 25 other species of fishes tested representing 11 families. Three juveniles were recovered from Gambusia holbrooki resulting in a metamorphosis rate <1%. We characterize P. jonesi as a host-fish specialist that fractionally releases conglutinates from late January to early June. Intact P. jonesi conglutinates resemble simuliid fly larvae attached to an egg-like structure, but most conglutinates were released as segments representing separate egg or larva mimics. Viability of glochidia encased within a conglutinate was >90% for ≥5 d. Feeding conglutinates directly to fishes allowed us to estimate seminatural infestation rates and calculate average numbers of juveniles produced per conglutinate, unlike the traditional approach of infesting fish hosts in an inoculation bath. Regressions based on the physical dimensions of each conglutinate or conglutinate segment were the most practical method used to estimate fecundity. Species distribution information, early life-history description, and methods developed for determining fecundity and conducting host trials may assist in the conservation of P. jonesi during recovery options that include captive propagation, augmentation, and reestablishment.

Host Fish Identification and Early Life Thermal Requirements for the Federal Endangered Winged Mapleleaf Mussel

USGS Publications Warehouse

Steingraeber, Mark; Newton, Teresa J.

2005-01-01

The winged mapleleaf mussel (Quadrula fragosa, WML) is a Federal endangered species historically inhabiting at least 34 river systems in 12 Midwestern states. Only four populations are currently known to exist, including one confirmed reproducing population in the St. Croix National Scenic Riverway (NSR) bordering Minnesota and Wisconsin. Recovery efforts are limited by a lack of life history information, particularly which species of fish serve as host to the mussel's parasitic larvae (glochidia). Since 1997, biologists at the University of Minnesota have tried to identify host fish for the WML. Department of the Interior colleagues working in western Wisconsin at the U.S. Fish and Wildlife Service's La Crosse Fishery Resources Office and Genoa National Fish Hatchery, the National Park Service's St. Croix NSR, and the U.S. Geological Survey's Upper Midwest Environmental Sciences Center (UMESC) in La Crosse joined the team in 2001 to expand and accelerate the laboratory host fish identification program by making use of the well-equipped aquatic research facilities at UMESC. We report on several WML early life history investigations conducted at UMESC since autumn 2003 to identify suitable host fish species and evaluate thermal requisites for the development of glochidia into free-living juvenile mussels.

Host plant species determines symbiotic bacterial community mediating suppression of plant defenses

USDA-ARS?s Scientific Manuscript database

Herbivore associated bacteria are vital mediators of plant and insect interactions. Host plants play an important role in shaping the gut bacterial community of insects. Colorado potato beetles (CPB; Leptinotarsa decemlineata) use several Solanum plants as hosts in their natural environment. We prev...

Systemic bacterial infection and immune defense phenotypes in Drosophila melanogaster.

PubMed

Khalil, Sarah; Jacobson, Eliana; Chambers, Moria C; Lazzaro, Brian P

2015-05-13

The fruit fly Drosophila melanogaster is one of the premier model organisms for studying the function and evolution of immune defense. Many aspects of innate immunity are conserved between insects and mammals, and since Drosophila can readily be genetically and experimentally manipulated, they are powerful for studying immune system function and the physiological consequences of disease. The procedure demonstrated here allows infection of flies by introduction of bacteria directly into the body cavity, bypassing epithelial barriers and more passive forms of defense and allowing focus on systemic infection. The procedure includes protocols for the measuring rates of host mortality, systemic pathogen load, and degree of induction of the host immune system. This infection procedure is inexpensive, robust and quantitatively repeatable, and can be used in studies of functional genetics, evolutionary life history, and physiology.

Plant defense response against Fusarium oxysporum and strategies to develop tolerant genotypes in banana.

PubMed

Swarupa, V; Ravishankar, K V; Rekha, A

2014-04-01

Soil-borne fungal pathogen, Fusarium oxysporum causes major economic losses by inducing necrosis and wilting symptoms in many crop plants. Management of fusarium wilt is achieved mainly by the use of chemical fungicides which affect the soil health and their efficiency is often limited by pathogenic variability. Hence understanding the nature of interaction between pathogen and host may help to select and improve better cultivars. Current research evidences highlight the role of oxidative burst and antioxidant enzymes indicating that ROS act as an important signaling molecule in banana defense response against Fusarium oxysporum f.sp. cubense. The role of jasmonic acid signaling in plant defense against necrotrophic pathogens is well recognized. But recent studies show that the role of salicylic acid is complex and ambiguous against necrotrophic pathogens like Fusarium oxysporum, leading to many intriguing questions about its relationship between other signaling compounds. In case of banana, a major challenge is to identify specific receptors for effector proteins like SIX proteins and also the components of various signal transduction pathways. Significant progress has been made to uncover the role of defense genes but is limited to only model plants such as Arabidopsis and tomato. Keeping this in view, we review the host response, pathogen diversity, current understanding of biochemical and molecular changes that occur during host and pathogen interaction. Developing resistant cultivars through mutation, breeding, transgenic and cisgenic approaches have been discussed. This would help us to understand host defenses against Fusarium oxysporum and to formulate strategies to develop tolerant cultivars.

MicroRNA regulated defense responses in Triticum aestivum L. during Puccinia graminis f.sp. tritici infection.

PubMed

Gupta, Om Prakash; Permar, Vipin; Koundal, Vikas; Singh, Uday Dhari; Praveen, Shelly

2012-02-01

Plants have evolved diverse mechanism to recognize pathogen attack and triggers defense responses. These defense responses alter host cellular function regulated by endogenous, small, non-coding miRNAs. To understand the mechanism of miRNAs regulated cellular functions during stem rust infection in wheat, we investigated eight different miRNAs viz. miR159, miR164, miR167, miR171, miR444, miR408, miR1129 and miR1138, involved in three different independent cellular defense response to infection. The investigation reveals that at the initiation of disease, accumulation of miRNAs might be playing a key role in hypersensitive response (HR) from host, which diminishes at the maturation stage. This suggests a possible host-fungal synergistic relation leading to susceptibility. Differential expression of these miRNAs in presence and absence of R gene provides a probable explanation of miRNA regulated R gene mediated independent pathways.

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.

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose

PubMed Central

Auld, Stuart K. J. R; Edel, Kai H.; Little, Tom J.

2013-01-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. PMID:23025616

A Virulence Essential CRN Effector of Phytophthora capsici Suppresses Host Defense and Induces Cell Death in Plant Nucleus.

PubMed

Mafurah, Joseph Juma; Ma, Huifei; Zhang, Meixiang; Xu, Jing; He, Feng; Ye, Tingyue; Shen, Danyu; Chen, Yanyu; Rajput, Nasir Ahmed; Dou, Daolong

2015-01-01

Phytophthora capsici is a soil-borne plant pathogen with a wide range of hosts. The pathogen secretes a large array of effectors during infection of host plants, including Crinkler (CRN) effectors. However, it remains largely unknown on the roles of these effectors in virulence especially in P. capsici. In this study, we identified a cell death-inducing CRN effector PcCRN4 using agroinfiltration approach. Transient expression of PcCRN4 gene induced cell death in N. benthamiana, N. tabacum and Solanum lycopersicum. Overexpression of the gene in N. benthamiana enhanced susceptibility to P. capsici. Subcellular localization results showed that PcCRN4 localized to the plant nucleus, and the localization was required for both of its cell death-inducing activity and virulent function. Silencing PcCRN4 gene in P. capsici significantly reduced pathogen virulence. The expression of the pathogenesis-related gene PR1b in N. benthamiana was significantly induced when plants were inoculated with PcCRN4-silenced P. capsici transformant compared to the wilt-type. Callose deposits were also abundant at sites inoculated with PcCRN4-silenced transformant, indicating that silencing of PcCRN4 in P. capsici reduced the ability of the pathogen to suppress plant defenses. Transcriptions of cell death-related genes were affected when PcCRN4-silenced line were inoculated on Arabidopsis thaliana, suggesting that PcCRN4 may induce cell death by manipulating cell death-related genes. Overall, our results demonstrate that PcCRN4 is a virulence essential effector and it needs target to the plant nucleus to suppress plant immune responses.

Anti-endotoxic and antibacterial effects of a dermal substitute coated with host defense peptides.

PubMed

Kasetty, Gopinath; Kalle, Martina; Mörgelin, Matthias; Brune, Jan C; Schmidtchen, Artur

2015-01-01

Biomaterials used during surgery and wound treatment are of increasing importance in modern medical care. In the present study we set out to evaluate the addition of thrombin-derived host defense peptides to human acellular dermis (hAD, i.e. epiflex(®)). Antimicrobial activity of the functionalized hAD was demonstrated using radial diffusion and viable count assays against Gram-negative Escherichia coli, Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus bacteria. Electron microscopy analyses showed that peptide-mediated bacterial killing led to reduced hAD degradation. Furthermore, peptide-functionalized hAD displayed endotoxin-binding activity in vitro, as evidenced by inhibition of NF-κB activation in human monocytic cells (THP-1 cells) and a reduction of pro-inflammatory cytokine production in whole blood in response to lipopolysaccharide stimulation. The dermal substitute retained its anti-endotoxic activity after washing, compatible with results showing that the hAD bound a significant amount of peptide. Furthermore, bacteria-induced contact activation was inhibited by peptide addition to the hAD. E. coli infected hAD, alone, or after treatment with the antiseptic substance polyhexamethylenebiguanide (PHMB), yielded NF-κB activation in THP-1 cells. The activation was abrogated by peptide addition. Thus, thrombin-derived HDPs should be of interest in the further development of new biomaterials with combined antimicrobial and anti-endotoxic functions for use in surgery and wound treatment. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Iron metabolism at the host pathogen interface: lipocalin 2 and the pathogen-associated iroA gene cluster.

PubMed

Smith, Kelly D

2007-01-01

The host innate immune defense protein lipocalin 2 binds bacterial enterobactin siderophores to limit bacterial iron acquisition. To counteract this host defense mechanism bacteria have acquired the iroA gene cluster, which encodes enzymatic machinery and transporters that revitalize enterobactin in the form of salmochelin. The iroB enzyme introduces glucosyl residues at the C5 site on 2,3-dihydroxybenzoylserine moieties of enterobactin and thereby prevents lipocalin 2 binding. Additional strategies to evade lipocalin 2 have evolved in other bacteria, such as Mycobacteria tuberculosis and Bacillus anthracis. Targeting these specialized bacterial evasion strategy may provide a mechanism to reinvigorate lipocalin 2 in defense against specific pathogens.

The exploitation of an ant-defended host plant by a shelter-building herbivore.

PubMed

Eubanks, Micky D; Nesci, Kimberly A; Petersen, Mette K; Liu, Zhiwei; Sanchez, Horacio Bonfil

1997-02-01

Larvae of a Polyhymno species (Lepidoptera: Gelechiidae) feed on the ant-defended acacia, Acacia cornigera, in the tropical lowlands of Veracruz, Mexico. Polyhymno larvae construct sealed shelters by silking together the pinna or pinnules of acacia leaves. Although larval density and larval survival are higher on acacias not occupied by ants, shelters serve as a partial refuge from the ant Pseudomyrmex ferruginea (Hymenoptera: Formicidae), which defends A. cornigera plants; thus, shelters provide Polyhymno larvae access to an ant-defended host plant. P. ferruginea ants act as the primary antiherbivore defense of A. cornigera plants, which lack the chemical and mechanical defenses of non-ant-defended acacias. Thus, defeating the ant defense of A. cornigera provides Polyhymno larvae access to an otherwise poorly defended host plant. Damage caused by Polyhymno larval feeding reaches levels which can kill A. cornigera plants.

Complement factor H in host defense and immune evasion.

PubMed

Parente, Raffaella; Clark, Simon J; Inforzato, Antonio; Day, Anthony J

2017-05-01

Complement is the major humoral component of the innate immune system. It recognizes pathogen- and damage-associated molecular patterns, and initiates the immune response in coordination with innate and adaptive immunity. When activated, the complement system unleashes powerful cytotoxic and inflammatory mechanisms, and thus its tight control is crucial to prevent damage to host tissues and allow restoration of immune homeostasis. Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response. Here we review recent (and not so recent) literature on the structure and function of factor H, including the emerging roles of this protein in the pathophysiology of infectious diseases and cancer.

A Host Susceptibility Gene, DR1, Facilitates Influenza A Virus Replication by Suppressing Host Innate Immunity and Enhancing Viral RNA Replication

PubMed Central

Hsu, Shih-Feng; Su, Wen-Chi; Jeng, King-Song

2015-01-01

ABSTRACT Influenza A virus (IAV) depends on cellular factors to complete its replication cycle; thus, investigation of the factors utilized by IAV may facilitate antiviral drug development. To this end, a cellular transcriptional repressor, DR1, was identified from a genome-wide RNA interference (RNAi) screen. Knockdown (KD) of DR1 resulted in reductions of viral RNA and protein production, demonstrating that DR1 acts as a positive host factor in IAV replication. Genome-wide transcriptomic analysis showed that there was a strong induction of interferon-stimulated gene (ISG) expression after prolonged DR1 KD. We found that beta interferon (IFN-β) was induced by DR1 KD, thereby activating the JAK-STAT pathway to turn on ISG expression, which led to a strong inhibition of IAV replication. This result suggests that DR1 in normal cells suppresses IFN induction, probably to prevent undesired cytokine production, but that this suppression may create a milieu that favors IAV replication once cells are infected. Furthermore, biochemical assays of viral RNA replication showed that DR1 KD suppressed viral RNA replication. We also showed that DR1 associated with all three subunits of the viral RNA-dependent RNA polymerase (RdRp) complex, indicating that DR1 may interact with individual components of the viral RdRp complex to enhance viral RNA replication. Thus, DR1 may be considered a novel host susceptibility gene for IAV replication via a dual mechanism, not only suppressing the host defense to indirectly favor IAV replication but also directly facilitating viral RNA replication. IMPORTANCE Investigations of virus-host interactions involved in influenza A virus (IAV) replication are important for understanding viral pathogenesis and host defenses, which may manipulate influenza virus infection or prevent the emergence of drug resistance caused by a high error rate during viral RNA replication. For this purpose, a cellular transcriptional repressor, DR1, was identified from

Identification of Novel Host Interactors of Effectors Secreted by Salmonella and Citrobacter

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

Sontag, Ryan L.; Nakayasu, Ernesto S.; Brown, Roslyn N.

Many pathogenic bacteria of the familyEnterobacteriaceaeuse type III secretion systems to inject virulence proteins, termed “effectors,” into the host cell cytosol. Although host-cellular activities of several effectors have been demonstrated, the function and host-targeted pathways of most of the effectors identified to date are largely undetermined. To gain insight into host proteins targeted by bacterial effectors, we performed coaffinity purification of host proteins from cell lysates using recombinant effectors from theEnterobacteriaceaeintracellular pathogensSalmonella entericaserovar Typhimurium andCitrobacter rodentium. We identified 54 high-confidence host interactors for theSalmonellaeffectors GogA, GtgA, GtgE, SpvC, SrfH, SseL, SspH1, and SssB collectively and 21 interactors for theCitrobactereffectors EspT,more » NleA, NleG1, and NleK. We biochemically validated the interaction between the SrfHSalmonellaprotein and the extracellular signal-regulated kinase 2 (ERK2) host protein kinase, which revealed a role for this effector in regulating phosphorylation levels of this enzyme, which plays a central role in signal transduction. IMPORTANCEDuring infection, pathogenic bacteria face an adverse environment of factors driven by both cellular and humoral defense mechanisms. To help evade the immune response and ultimately proliferate inside the host, many bacteria evolved specialized secretion systems to deliver effector proteins directly into host cells. Translocated effector proteins function to subvert host defense mechanisms. Numerous pathogenic bacteria use a specialized secretion system called type III secretion to deliver effectors into the host cell cytosol. Here, we identified 75 new host targets ofSalmonellaandCitrobactereffectors, which will help elucidate their mechanisms of action.« less

Host-Induced gene silencing in barley powdery mildew reveals a class of ribonuclease-like effectors

USDA-ARS?s Scientific Manuscript database

Obligate biotrophic pathogens of plants require the ability to circumvent host defenses to enable colonization. To establish compatibility, pathogens secrete a variety of effectors, which regulate host immunity, and thus, facilitate the establishment of haustorial feeding structures. These structur...

A novel nematode effector suppresses plant immunity by activating host reactive oxygen species-scavenging system.

PubMed

Lin, Borong; Zhuo, Kan; Chen, Shiyan; Hu, Lili; Sun, Longhua; Wang, Xiaohong; Zhang, Lian-Hui; Liao, Jinling

2016-02-01

Evidence is emerging that plant-parasitic nematodes can secrete effectors to interfere with the host immune response, but it remains unknown how these effectors can conquer host immune responses. Here, we depict a novel effector, MjTTL5, that could suppress plant immune response. Immunolocalization and transcriptional analyses showed that MjTTL5 is expressed specifically within the subventral gland of Meloidogyne javanica and up-regulated in the early parasitic stage of the nematode. Transgenic Arabidopsis lines expressing MjTTL5 were significantly more susceptible to M. javanica infection than wild-type plants, and vice versa, in planta silencing of MjTTL5 substantially increased plant resistance to M. javanica. Yeast two-hybrid, coimmunoprecipitation and bimolecular fluorescent complementation assays showed that MjTTL5 interacts specifically with Arabidopsis ferredoxin : thioredoxin reductase catalytic subunit (AtFTRc), a key component of host antioxidant system. The expression of AtFTRc is induced by the infection of M. javanica. Interaction between AtFTRc and MjTTL could drastically increase host reactive oxygen species-scavenging activity, and result in suppression of plant basal defenses and attenuation of host resistance to the nematode infection. Our results demonstrate that the host ferredoxin : thioredoxin system can be exploited cunningly by M. javanica, revealing a novel mechanism utilized by plant-parasitic nematodes to subjugate plant innate immunity and thereby promoting parasitism. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

A cluster of immunoresolvents links coagulation to innate host defense in human blood.

PubMed

Norris, Paul C; Libreros, Stephania; Chiang, Nan; Serhan, Charles N

2017-08-01

Blood coagulation is a protective response that prevents excessive bleeding upon blood vessel injury. We investigated the relationship between coagulation and the resolution of inflammation and infection by lipid mediators (LMs) through metabololipidomics-based profiling of human whole blood (WB) during coagulation. We identified temporal clusters of endogenously produced prothrombotic and proinflammatory LMs (eicosanoids), as well as specialized proresolving mediators (SPMs). In addition to eicosanoids, a specific SPM cluster was identified that consisted of resolvin E1 (RvE1), RvD1, RvD5, lipoxin B 4 , and maresin 1, each of which was present at bioactive concentrations (0.1 to 1 nM). Removal of adenosine from the coagulating blood markedly enhanced the amounts of SPMs produced and further increased the biosynthesis of RvD3, RvD4, and RvD6. The cyclooxygenase inhibitors celecoxib and indomethacin, which block the production of thromboxanes and prostanoids, did not block the production of clot-driven SPMs. Unbiased mass cytometry analysis demonstrated that the SPM cluster produced in human blood targeted leukocytes at the single-cell level, directly activating ERK and CREB signaling in neutrophils and CD14 + monocytes. Treatment of human WB with the components of this SPM cluster enhanced both the phagocytosis and killing of Escherichia coli by leukocytes. Together, these data identify a proresolving LM circuit, including endogenous molecular brakes and accelerators, which promoted host defense. These temporal LM-SPM clusters can provide accessible metabolomic profiles for precision and personalized medicine. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The role of body size in host specificity: reciprocal transfer experiments with feather lice.

PubMed

Bush, Sarah E; Clayton, Dale H

2006-10-01

Although most parasites show at least some degree of host specificity, factors governing the evolution of specificity remain poorly understood. Many different groups of host-specific parasites show a striking correlation between parasite and host body size, suggesting that size reinforces specificity. We tested this hypothesis by measuring the relative fitness of host-specific feather lice transferred to pigeons and doves that differ in size by an order of magnitude. To test the general influence of size, we transferred unrelated groups of wing and body lice, which are specialized for different regions of the host. Lice were transferred in both directions, from a large native host species, the rock pigeon (Columba livia), to several progressively smaller hosts, and from a small native host species, the common ground dove (Columbina passerina), to several larger hosts. We measured the relative fitness (population size) of lice transferred to these novel host species after two louse generations. Neither wing lice nor body lice could survive on novel host species that were smaller in size than the native host. However, when host defense (preening behavior) was blocked, both groups survived and reproduced on all novel hosts tested. Thus, host defense interacted with host size to govern the ability of lice to establish on small hosts. Neither wing lice nor body lice could survive on larger hosts, even when preening was blocked. In summary, host size influenced the fitness of both types of feather lice, but through different mechanisms, depending on the direction of the transfer. Our results indicate that host switching is most likely between hosts of similar body size. This finding has important implications for studies of host-parasite coevolution at both the micro- and macroevolutionary scales.

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.

Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense

PubMed Central

Wang, Xing; Li, Yun; Liu, Shan; Yu, Xiaoliang; Li, Lin; Shi, Cuilin; He, Wenhui; Li, Jun; Xu, Lei; Hu, Zhilin; Yu, Lu; Yang, Zhongxu; Chen, Qin; Ge, Lin; Zhang, Zili; Zhou, Biqi; Jiang, Xuejun; Chen, She; He, Sudan

2014-01-01

The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6–RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1–infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism. PMID:25316792

Molecular functions of Xanthomonas type III effector AvrBsT and its plant interactors in cell death and defense signaling.

PubMed

Han, Sang Wook; Hwang, Byung Kook

2017-02-01

Xanthomonas effector AvrBsT interacts with plant defense proteins and triggers cell death and defense response. This review highlights our current understanding of the molecular functions of AvrBsT and its host interactor proteins. The AvrBsT protein is a member of a growing family of effector proteins in both plant and animal pathogens. Xanthomonas type III effector AvrBsT, a member of the YopJ/AvrRxv family, suppresses plant defense responses in susceptible hosts, but triggers cell death signaling leading to hypersensitive response (HR) and defense responses in resistant plants. AvrBsT interacts with host defense-related proteins to trigger the HR cell death and defense responses in plants. Here, we review and discuss recent progress in understanding the molecular functions of AvrBsT and its host interactor proteins in pepper (Capsicum annuum). Pepper arginine decarboxylase1 (CaADC1), pepper aldehyde dehydrogenase1 (CaALDH1), pepper heat shock protein 70a (CaHSP70a), pepper suppressor of the G2 allele of skp1 (CaSGT1), pepper SNF1-related kinase1 (SnRK1), and Arabidopsis acetylated interacting protein1 (ACIP1) have been identified as AvrBsT interactors in pepper and Arabidopsis. Gene expression profiling, virus-induced gene silencing, and transient transgenic overexpression approaches have advanced the functional characterization of AvrBsT-interacting proteins in plants. AvrBsT is localized in the cytoplasm and forms protein-protein complexes with host interactors. All identified AvrBsT interactors regulate HR cell death and defense responses in plants. Notably, CaSGT1 physically binds to both AvrBsT and pepper receptor-like cytoplasmic kinase1 (CaPIK1) in the cytoplasm. During infection with Xanthomonas campestris pv. vesicatoria strain Ds1 (avrBsT), AvrBsT is phosphorylated by CaPIK1 and forms the active AvrBsT-CaSGT1-CaPIK1 complex, which ultimately triggers HR cell death and defense responses. Collectively, the AvrBsT interactor proteins are involved in plant

The entomopathogenic fungus Metarhizium robertsii communicates with the insect host Galleria mellonella during infection.

PubMed

Mukherjee, Krishnendu; Vilcinskas, Andreas

2018-01-01

Parasitic fungi are the only pathogens that can infect insect hosts directly through their proteinaceous exoskeleton. Penetration of the cuticle requires the release of fungal enzymes, including proteinases, which act as virulence factors. Insects can sense fungal infections and activate innate immune responses, including the synthesis of antifungal peptides and proteinase inhibitors that neutralize the incoming proteinases. This well-studied host response is epigenetically regulated by histone acetylation/deacetylation. Here we show that entomopathogenic fungi can in turn sense the presence of insect-derived antifungal peptides and proteinase inhibitors, and respond by inducing the synthesis of chymotrypsin-like proteinases and metalloproteinases that degrade the host-derived defense molecules. The rapidity of this response is dependent on the virulence of the fungal strain. We confirmed the specificity of the pathogen response to host-derived defense molecules by LC/MS and RT-PCR analysis, and correlated this process with the epigenetic regulation of histone acetylation/deacetylation. This cascade of responses reveals that the coevolution of pathogens and hosts can involve a complex series of attacks and counterattacks based on communication between the invading fungal pathogen and its insect host. The resolution of this process determines whether or not pathogenesis is successful.

Demeter's Resilience: an International Food Defense exercise.

PubMed

Hennessey, Morgan; Kennedy, Shaun; Busta, Frank

2010-07-01

The National Center for Food Protection and Defense (NCFPD), which is led by the University of Minnesota, hosted an international food defense exercise on 27 to 29 May 2008. Established in 2004, NCFPD is a Department of Homeland Security Center of Excellence with the mission of defending the food system through research and education. Tabletop exercises are practice-based scenarios intended to mimic real life experiences. The objective of the exercise discussed in this article was to facilitate discussion to increase awareness among exercise participants of both the threat that would be posed by an intentional attack on the food supply and the international impact of such an attack. Through facilitated discussion, exercise participants agreed on the following themes: (i) recognition of a foodborne disease outbreak is driven by the characteristics of the illness rather than the actual number of ill individuals; (ii) during the course of a foodborne outbreak there are generally multiple levels of communication; (iii) a common case definition for a foodborne disease is difficult to develop on a global scale; and (iv) the safety and health of all individuals is the number one priority of all parties involved. Several challenges were faced during the development of the exercise, but these were overcome to produce a more robust exercise. The following discussion will provide an overview of the challenges and the strategies used to overcome them. The lessons learned provide insight into how to plan, prepare, and host an international food defense exercise.

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

PubMed

Auld, Stuart K J R; Edel, Kai H; Little, Tom J

2012-10-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

Natural selection on immune defense: A field experiment.

PubMed

Langeloh, Laura; Behrmann-Godel, Jasminca; Seppälä, Otto

2017-02-01

Predicting the evolution of phenotypic traits requires an understanding of natural selection on them. Despite its indispensability in the fight against parasites, selection on host immune defense has remained understudied. Theory predicts immune traits to be under stabilizing selection due to associated trade-offs with other fitness-related traits. Empirical studies, however, report mainly positive directional selection. This discrepancy could be caused by low phenotypic variation in the examined individuals and/or variation in host resource level that confounds trade-offs in empirical studies. In a field experiment where we maintained Lymnaea stagnalis snails individually in cages in a lake, we investigated phenotypic selection on two immune defense traits, phenoloxidase (PO)-like activity and antibacterial activity, in hemolymph. We used a diverse laboratory population and manipulated snail resource level by limiting their food supply. For six weeks, we followed immune activity, growth, and two fitness components, survival and fecundity of snails. We found that PO-like activity and growth were under stabilizing selection, while antibacterial activity was under positive directional selection. Selection on immune traits was mainly driven by variation in survival. The form of selection on immune defense apparently depends on the particular trait, possibly due to its importance for countering the present parasite community. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Comprehensive Genetic Analysis of Early Host Body Reactions to the Bioactive and Bio-Inert Porous Scaffolds

PubMed Central

Ehashi, Tomo; Takemura, Taro; Hanagata, Nobutaka; Minowa, Takashi; Kobayashi, Hisatoshi; Ishihara, Kazuhiko; Yamaoka, Tetsuji

2014-01-01

To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied. There is no information about host body reactions that can predict successful tissue regeneration in the future. In the present study, porous polyethylene scaffolds were coated with bioactive collagen or bio-inert poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) (PMB) and were implanted subcutaneously and compared the host body reaction to those substrates by normalizing the result using control non-coat polyethylene scaffold. The comprehensive analyses of early host body reactions to the scaffolds were carried out using a DNA microarray assay. Within numerous genes which were expressed differently among these scaffolds, particular genes related to inflammation, wound healing, and angiogenesis were focused upon. Interleukin (IL)-1β and IL-10 are important cytokines in tissue responses to biomaterials because IL-1β promotes both inflammation and wound healing and IL-10 suppresses both of them. IL-1β was up-regulated in the collagen-coated scaffold. Collagen-specifically up-regulated genes contained both M1- and M2-macrophage-related genes. Marked vessel formation in the collagen-coated scaffold was occurred in accordance with the up-regulation of many angiogenesis-inducible factors. The DNA microarray assay provided global information regarding the host body reaction. Interestingly, several up-regulated genes were detected even on the very bio-inert PMB-coated surfaces and those genes include inflammation-suppressive and wound healing-suppressive IL-10, suggesting that not only active tissue response but also the inert response may relates to these genetic regulations. PMID:24454803

Master manipulators: an update on Legionella pneumophila Icm/Dot translocated substrates and their host targets

PubMed Central

Isaac, Dervla T; Isberg, Ralph

2014-01-01

Macrophages are the front line of immune defense against invading microbes. Microbes, however, have evolved numerous and diverse mechanisms to thwart these host immune defenses and thrive intracellularly. Legionella pneumophila, a Gram-negative pathogen of amoebal and mammalian phagocytes, is one such microbe. In humans, it causes a potentially fatal pneumonia referred to as Legionnaires' disease. Armed with the Icm/Dot type IV secretion system, which is required for virulence, and approximately 300 translocated proteins, Legionella is able to enter host cells, direct the biogenesis of its own vacuolar compartment, and establish a replicative niche, where it grows to high levels before lysing the host cell. Efforts to understand the pathogenesis of this bacterium have focused on characterizing the molecular activities of its many effectors. In this article, we highlight recent strides that have been made in understanding how Legionella effectors mediate host-pathogen interactions. PMID:24762308

Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature.

PubMed

Foxman, Ellen F; Storer, James A; Vanaja, Kiran; Levchenko, Andre; Iwasaki, Akiko

2016-07-26

Most strains of rhinovirus (RV), the common cold virus, replicate better at cool temperatures found in the nasal cavity (33-35 °C) than at lung temperature (37 °C). Recent studies found that although 37 °C temperature suppressed RV growth largely by engaging the type 1 IFN response in infected epithelial cells, a significant temperature dependence to viral replication remained in cells devoid of IFN induction or signaling. To gain insight into IFN-independent mechanisms limiting RV replication at 37 °C, we studied RV infection in human bronchial epithelial cells and H1-HeLa cells. During the single replication cycle, RV exhibited temperature-dependent replication in both cell types in the absence of IFN induction. At 37 °C, earlier signs of apoptosis in RV-infected cells were accompanied by reduced virus production. Furthermore, apoptosis of epithelial cells was enhanced at 37 °C in response to diverse stimuli. Dynamic mathematical modeling and B cell lymphoma 2 (BCL2) overexpression revealed that temperature-dependent host cell death could partially account for the temperature-dependent growth observed during RV amplification, but also suggested additional mechanisms of virus control. In search of a redundant antiviral pathway, we identified a role for the RNA-degrading enzyme RNAseL. Simultaneous antagonism of apoptosis and RNAseL increased viral replication and dramatically reduced temperature dependence. These findings reveal two IFN-independent mechanisms active in innate defense against RV, and demonstrate that even in the absence of IFNs, temperature-dependent RV amplification is largely a result of host cell antiviral restriction mechanisms operating more effectively at 37 °C than at 33 °C.

Glucosinolates from Host Plants Influence Growth of the Parasitic Plant Cuscuta gronovii and Its Susceptibility to Aphid Feeding.

PubMed

Smith, Jason D; Woldemariam, Melkamu G; Mescher, Mark C; Jander, Georg; De Moraes, Consuelo M

2016-09-01

Parasitic plants acquire diverse secondary metabolites from their hosts, including defense compounds that target insect herbivores. However, the ecological implications of this phenomenon, including the potential enhancement of parasite defenses, remain largely unexplored. We studied the translocation of glucosinolates from the brassicaceous host plant Arabidopsis (Arabidopsis thaliana) into parasitic dodder vines (Convolvulaceae; Cuscuta gronovii) and its effects on the parasite itself and on dodder-aphid interactions. Aliphatic and indole glucosinolates reached concentrations in parasite tissues higher than those observed in corresponding host tissues. Dodder growth was enhanced on cyp79B2 cyp79B3 hosts (without indole glucosinolates) but inhibited on atr1D hosts (with elevated indole glucosinolates) relative to wild-type hosts, which responded to parasitism with localized elevation of indole and aliphatic glucosinolates. These findings implicate indole glucosinolates in defense against parasitic plants. Rates of settling and survival on dodder vines by pea aphids (Acyrthosiphon pisum) were reduced significantly when dodder parasitized glucosinolate-producing hosts (wild type and atr1D) compared with glucosinolate-free hosts (cyp79B2 cyp79B3 myb28 myb29). However, settling and survival of green peach aphids (Myzus persicae) were not affected. M. persicae population growth was actually reduced on dodder parasitizing glucosinolate-free hosts compared with wild-type or atr1D hosts, even though stems of the former contain less glucosinolates and more amino acids. Strikingly, this effect was reversed when the aphids fed directly upon Arabidopsis, which indicates an interactive effect of parasite and host genotype on M. persicae that stems from host effects on dodder. Thus, our findings indicate that glucosinolates may have both direct and indirect effects on dodder-feeding herbivores. © 2016 American Society of Plant Biologists. All rights reserved.

Ternary nylon-3 copolymers as host-defense peptide mimics: beyond hydrophobic and cationic subunits.

PubMed

Chakraborty, Saswata; Liu, Runhui; Hayouka, Zvi; Chen, Xinyu; Ehrhardt, Jeffrey; Lu, Qin; Burke, Eileen; Yang, Yiqing; Weisblum, Bernard; Wong, Gerard C L; Masters, Kristyn S; Gellman, Samuel H

2014-10-15

Host-defense peptides (HDPs) are produced by eukaryotes to defend against bacterial infection, and diverse synthetic polymers have recently been explored as mimics of these natural peptides. HDPs are rich in both hydrophobic and cationic amino acid residues, and most HDP-mimetic polymers have therefore contained binary combinations of hydrophobic and cationic subunits. However, HDP-mimetic polymers rarely duplicate the hydrophobic surface and cationic charge density found among HDPs ( Hu , K. ; et al. Macromolecules 2013 , 46 , 1908 ); the charge and hydrophobicity are generally higher among the polymers. Statistical analysis of HDP sequences ( Wang , G. ; et al. Nucleic Acids Res. 2009 , 37 , D933 ) has revealed that serine (polar but uncharged) is a very common HDP constituent and that glycine is more prevalent among HDPs than among proteins in general. These observations prompted us to prepare and evaluate ternary nylon-3 copolymers that contain a modestly polar but uncharged subunit, either serine-like or glycine-like, along with a hydrophobic subunit and a cationic subunit. Starting from binary hydrophobic-cationic copolymers that were previously shown to be highly active against bacteria but also highly hemolytic, we found that replacing a small proportion of the hydrophobic subunit with either of the polar, uncharged subunits can diminish the hemolytic activity with minimal impact on the antibacterial activity. These results indicate that the incorporation of polar, uncharged subunits may be generally useful for optimizing the biological activity profiles of antimicrobial polymers. In the context of HDP evolution, our findings suggest that there is a selective advantage to retaining polar, uncharged residues in natural antimicrobial peptides.

GALAXY ZOO: THE FUNDAMENTALLY DIFFERENT CO-EVOLUTION OF SUPERMASSIVE BLACK HOLES AND THEIR EARLY- AND LATE-TYPE HOST GALAXIES

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

Schawinski, Kevin; Urry, C. Megan; Virani, Shanil

We use data from the Sloan Digital Sky Survey and visual classifications of morphology from the Galaxy Zoo project to study black hole growth in the nearby universe (z < 0.05) and to break down the active galactic nucleus (AGN) host galaxy population by color, stellar mass, and morphology. We find that the black hole growth at luminosities L[O{sub III}]>10{sup 40} erg s{sup -1} in early- and late-type galaxies is fundamentally different. AGN host galaxies as a population have a broad range of stellar masses (10{sup 10}-10{sup 11} M{sub sun}), reside in the green valley of the color-mass diagram andmore » their central black holes have median masses around 10{sup 6.5} M{sub sun}. However, by comparing early- and late-type AGN host galaxies to their non-active counterparts, we find several key differences: in early-type galaxies, it is preferentially the galaxies with the least massive black holes that are growing, while in late-type galaxies, it is preferentially the most massive black holes that are growing. The duty cycle of AGNs in early-type galaxies is strongly peaked in the green valley below the low-mass end (10{sup 10} M{sub sun}) of the red sequence at stellar masses where there is a steady supply of blue cloud progenitors. The duty cycle of AGNs in late-type galaxies on the other hand peaks in massive (10{sup 11} M{sub sun}) green and red late-types which generally do not have a corresponding blue cloud population of similar mass. At high-Eddington ratios (L/L{sub Edd}>0.1), the only population with a substantial fraction of AGNs are the low-mass green valley early-type galaxies. Finally, the Milky Way likely resides in the 'sweet spot' on the color-mass diagram where the AGN duty cycle of late-type galaxies is highest. We discuss the implications of these results for our understanding of the role of AGNs in the evolution of galaxies.« less

[Monoxenous and heteroxenous parasites of fish manipulate behavior of their hosts in different ways].

PubMed

Mikheev, V N

2011-01-01

Adaptive host manipulation hypothesis is usually supported by case studies on trophically transmitted heteroxenous endoparasites. Trematodes and cestodes are among efficient manipulators of fish, their common intermediate hosts. In this review paper, new data on modifications of host fish behavior caused by monoxenous ectoparasitic crustaceans are provided together with a review of effects caused by heteroxenous parasites. Differences in modifications of host behavior caused by heteroxenous and monoxenous parasites are discussed. Manipulation by heteroxenous parasites enhances availability of infected fish to predators--definitive hosts of the parasites. Fine-tuned synchronization of modified anti-predator behavior with a certain phase of the trematode Diplostomum spathaceum development in the eyes of fish, their second intermediate host, was shown. Modifications of behavior are habitat specific. When juvenile salmonids are in the open water, parasites impair their cooperative anti-predator behavior; in territorial bottom-dwelling salmonids, individual defense behavior such as sheltering is the main target of manipulation. It was shown that monoxenous ectoparasitic crustaceans Argulus spp. decreased motor activity, aggressiveness and increased shoal cohesiveness of infected fish. Such a behavior facilitates host and mate searching in these parasites, which often change their hosts, especially during reproduction. Reviewed experimental data suggest that heteroxenous parasites manipulate their host mainly through impaired defense behavior, e.g. impairing shoaling in fish. Alternatively, monoxenous parasites facilitate shoaling that is profitable for both parasites and hosts. Coordination of modified host behavior with the parasite life cycle, both temporal and spatial, is the most convincing criterion of the adaptive value of host manipulation.

Early intranuclear replication of African swine fever virus genome modifies the landscape of the host cell nucleus.

PubMed

Simões, Margarida; Martins, Carlos; Ferreira, Fernando

2015-12-02

Although African swine fever virus (ASFV) replicates in viral cytoplasmic factories, the presence of viral DNA within the host cell nucleus has been previously reported to be essential for productive infection. Herein, we described, for the first time, the intranuclear distribution patterns of viral DNA replication events, preceding those that occur in the cytoplasmic compartment. Using BrdU pulse-labelling experiments, newly synthesized ASFV genomes were exclusively detected inside the host cell nucleus at the early phase of infection, both in swine monocyte-derived macrophages (MDMs) and Vero cells. From 8hpi onwards, BrdU labelling was only observed in ASFV cytoplasmic factories. Our results also show that ASFV specifically activates the Ataxia Telangiectasia Mutated Rad-3 related (ATR) pathway in ASFV-infected swine MDMs from the early phase of infection, most probably because ASFV genome is recognized as foreign DNA. Morphological changes of promyelocytic leukaemia nuclear bodies (PML-NBs), nuclear speckles and Cajal bodies were also found in ASFV-infected swine MDMs, strongly suggesting the viral modulation of cellular antiviral responses and cellular transcription, respectively. As described for other viral infections, the nuclear reorganization that takes place during ASFV infection may also provide an environment that favours its intranuclear replication events. Altogether, our results contribute for a better understanding of ASFV replication strategies, starting with an essential intranuclear DNA replication phase which induces host nucleus changes towards a successful viral infection. Copyright © 2015 Elsevier B.V. All rights reserved.

Caterpillar chemical defense and parasitoid success: Cotesia congregata parasitism of Ceratomia catalpae.

PubMed

Lampert, Evan C; Dyer, Lee A; Bowers, M Deane

2010-09-01

Sequestration of plant compounds by herbivorous insects as a defense against predators is well documented; however, few studies have examined the effectiveness of sequestration as a defense against parasitoids. One assumption of the "nasty host" hypothesis is that sequestration of plant defense compounds is deleterious to parasitoid development. We tested this hypothesis with larvae of the sequestering sphingid Ceratomia catalpae, which is heavily parasitized by the endoparasitoid Cotesia congregata, despite sequestering high concentrations of the iridoid glycoside catalpol from their catalpa host plants. We collected C. catalpae and catalpa leaves from six populations in the Eastern US, and allowed any C. congregata to emerge in the lab. Leaf iridoid glycosides and caterpillar iridoid glycosides were quantified, and we examined associations between sequestered caterpillar iridoid glycosides and C. congregata performance. Caterpillar iridoid glycosides were not associated with C. congregata field parasitism or number of offspring produced. Although wasp survival was over 90% in all populations, there was a slight negative relationship between caterpillar iridoid glycosides and wasp survival. Iridoid glycosides were present in caterpillars at levels that are deterrent to a variety of vertebrate and invertebrate predators. Thus, our results support the alternative hypothesis that unpalatable, chemically defended hosts are "safe havens" for endoparasitoids. Future trials examining the importance of catalpol sequestration to potential natural enemies of C. congregata and C. catalpae are necessary to strengthen this conclusion.

Identification of cotton fleahopper (Hemiptera: Miridae) host plants in central Texas and compendium of reported hosts in the United States.

PubMed

Esquivel, J F; Esquivel, S V

2009-06-01

The cotton fleahopper, Pseudatomoscelis seriatus (Reuter), is an early-season pest of developing cotton in Central Texas and other regions of the Cotton Belt. Cotton fleahopper populations develop on spring weed hosts and move to cotton as weed hosts senesce or if other weed hosts are not readily available. To identify weed hosts that were seasonably available for the cotton fleahopper in Central Texas, blooming weed species were sampled during early-season (17 March-31 May), mid-season (1 June-14 August), late-season (15 August-30 November), and overwintering (1 December-16 March) periods. The leading hosts for cotton fleahopper adults and nymphs were evening primrose (Oenothera speciosa T. Nuttall) and Mexican hat [Ratibida columnifera (T. Nuttall) E. Wooton and P. Standley], respectively, during the early season. During the mid-season, silver-leaf nightshade (Solanum elaeagnifolium A. Cavanilles) was consistently a host for fleahopper nymphs and adults. Woolly croton (Croton capitatus A. Michaux) was a leading host during the late season. Cotton fleahoppers were not collected during the overwintering period. Other suitable hosts were available before previously reported leading hosts became available. Eight previously unreported weed species were documented as temporary hosts. A compendium of reported hosts, which includes >160 plant species representing 35 families, for the cotton fleahopper is provided for future research addressing insect-host plant associations. Leading plant families were Asteraceae, Lamiaceae, and Onagraceae. Results presented here indicate a strong argument for assessing weed species diversity and abundance for the control of the cotton fleahopper in the Cotton Belt.

Insights to host discrimination and host acceptance behaviour in a parasitoid (Diptera: Asilidae): implications for fitness.

PubMed

Crespo, José E; Castelo, Marcela K

2009-11-01

The robber fly Mallophora ruficauda is one of the principal pests of apiculture in the Pampas region of Argentina. As adults they prey on honey bees and other insects, while as larvae they are solitary ectoparasitoids of third instar scarab beetle larvae. Females of M. ruficauda lay eggs away from the host in tall grasses. After being dispersed by the wind, larvae drop to the ground, where they dig in search of their hosts. It is known that second instar larvae of M. ruficauda exhibit active host searching behaviour towards its preferred host, third instar larva of Cyclocephala signaticollis. Although the means by which host location occurs has been studied and since superparasitism is a frequent scenario in the field, no information about host discrimination and host acceptance is available. We carried out studies in the field and behavioural experiments in the laboratory to determine if M. ruficauda is capable of quality host discrimination. We also studied if this parasitoid is capable of conspecific detection in order to avoid superparasitism. Finally, we analyzed the conditions under which superparasitism occurs in the field. We report here that the second instar larva of M. ruficauda is able to discriminate the parasitism status of the host by means of chemical cues, but is not capable of detecting conspecifics prior to attacking a host. We also found that the host cannot detect the presence of the parasitoid by means of chemical cues, so that no counter-defense against parasitism occurs. Furthermore, we determined that superparasitism occurs on the heavier hosts, i.e. those with more abundant resources which could harbor several parasitoid individuals. Finally, we discuss the possible implications of larval host location and host discrimination decisions on the fitness of this parasitoid.

Massive activation of archaeal defense genes during viral infection.

PubMed

Quax, Tessa E F; Voet, Marleen; Sismeiro, Odile; Dillies, Marie-Agnes; Jagla, Bernd; Coppée, Jean-Yves; Sezonov, Guennadi; Forterre, Patrick; van der Oost, John; Lavigne, Rob; Prangishvili, David

2013-08-01

Archaeal viruses display unusually high genetic and morphological diversity. Studies of these viruses proved to be instrumental for the expansion of knowledge on viral diversity and evolution. The Sulfolobus islandicus rod-shaped virus 2 (SIRV2) is a model to study virus-host interactions in Archaea. It is a lytic virus that exploits a unique egress mechanism based on the formation of remarkable pyramidal structures on the host cell envelope. Using whole-transcriptome sequencing, we present here a global map defining host and viral gene expression during the infection cycle of SIRV2 in its hyperthermophilic host S. islandicus LAL14/1. This information was used, in combination with a yeast two-hybrid analysis of SIRV2 protein interactions, to advance current understanding of viral gene functions. As a consequence of SIRV2 infection, transcription of more than one-third of S. islandicus genes was differentially regulated. While expression of genes involved in cell division decreased, those genes playing a role in antiviral defense were activated on a large scale. Expression of genes belonging to toxin-antitoxin and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems was specifically pronounced. The observed different degree of activation of various CRISPR-Cas systems highlights the specialized functions they perform. The information on individual gene expression and activation of antiviral defense systems is expected to aid future studies aimed at detailed understanding of the functions and interplay of these systems in vivo.

Proteomic analyses of host and pathogen responses during bovine mastitis.

PubMed

Boehmer, Jamie L

2011-12-01

The pursuit of biomarkers for use as clinical screening tools, measures for early detection, disease monitoring, and as a means for assessing therapeutic responses has steadily evolved in human and veterinary medicine over the past two decades. Concurrently, advances in mass spectrometry have markedly expanded proteomic capabilities for biomarker discovery. While initial mass spectrometric biomarker discovery endeavors focused primarily on the detection of modulated proteins in human tissues and fluids, recent efforts have shifted to include proteomic analyses of biological samples from food animal species. Mastitis continues to garner attention in veterinary research due mainly to affiliated financial losses and food safety concerns over antimicrobial use, but also because there are only a limited number of efficacious mastitis treatment options. Accordingly, comparative proteomic analyses of bovine milk have emerged in recent years. Efforts to prevent agricultural-related food-borne illness have likewise fueled an interest in the proteomic evaluation of several prominent strains of bacteria, including common mastitis pathogens. The interest in establishing biomarkers of the host and pathogen responses during bovine mastitis stems largely from the need to better characterize mechanisms of the disease, to identify reliable biomarkers for use as measures of early detection and drug efficacy, and to uncover potentially novel targets for the development of alternative therapeutics. The following review focuses primarily on comparative proteomic analyses conducted on healthy versus mastitic bovine milk. However, a comparison of the host defense proteome of human and bovine milk and the proteomic analysis of common veterinary pathogens are likewise introduced.

Effects of larch defenses on xylophagous insect guilds

Treesearch

Galina I. Girs; Victor M. Yanovsky

1991-01-01

One of the best studies of a xylophage consortium is the case of larch insects by Isaev and Girs (1975). In their book, a basic theory was presented about host responses to xylophagous insects injury. According to their concept of "sliding resistance," different trunk-infesting insect species have different reactions to the tree's defenses and invade the...

Ca²⁺-dependent repair of pneumolysin pores: A new paradigm for host cellular defense against bacterial pore-forming toxins.

PubMed

Wolfmeier, Heidi; Schoenauer, Roman; Atanassoff, Alexander P; Neill, Daniel R; Kadioglu, Aras; Draeger, Annette; Babiychuk, Eduard B

2015-09-01

Pneumolysin (PLY), a key virulence factor of Streptococcus pneumoniae, permeabilizes eukaryotic cells by forming large trans-membrane pores. PLY imposes a puzzling multitude of diverse, often mutually excluding actions on eukaryotic cells. Whereas cytotoxicity of PLY can be directly attributed to the pore-mediated effects, mechanisms that are responsible for the PLY-induced activation of host cells are poorly understood. We show that PLY pores can be repaired and thereby PLY-induced cell death can be prevented. Pore-induced Ca²⁺ entry from the extracellular milieu is of paramount importance for the initiation of plasmalemmal repair. Nevertheless, active Ca²⁺ sequestration that prevents excessive Ca²⁺ elevation during the execution phase of plasmalemmal repair is of no less importance. The efficacy of plasmalemmal repair does not only define the fate of targeted cells but also intensity, duration and repetitiveness of PLY-induced Ca²⁺ signals in cells that were able to survive after PLY attack. Intracellular Ca²⁺ dynamics evoked by the combined action of pore formation and their elimination mimic the pattern of receptor-mediated Ca²⁺ signaling, which is responsible for the activation of host immune responses. Therefore, we postulate that plasmalemmal repair of PLY pores might provoke cellular responses that are similar to those currently ascribed to the receptor-mediated PLY effects. Our data provide new insights into the understanding of the complexity of cellular non-immune defense responses to a major pneumococcal toxin that plays a critical role in the establishment and the progression of life-threatening diseases. Therapies boosting plasmalemmal repair of host cells and their metabolic fitness might prove beneficial for the treatment of pneumococcal infections. This article is part of a Special Issue entitled: 13th European Symposium on Calcium. Copyright © 2014 Elsevier B.V. All rights reserved.

Extracellular matrix-associated proteome changes during non-host resistance in citrus-Xanthomonas interactions.

PubMed

Swaroopa Rani, Tirupaati; Podile, Appa Rao

2014-04-01

Non-host resistance (NHR) is a most durable broad-spectrum resistance employed by the plants to restrict majority of pathogens. Plant extracellular matrix (ECM) is a critical defense barrier. Understanding ECM responses during interaction with non-host pathogen will provide insights into molecular events of NHR. In this study, the ECM-associated proteome was compared during interaction of citrus with pathogen Xanthomonas axonopodis pv. citri (Xac) and non-host pathogen Xanthomonas oryzae pv. oryzae (Xoo) at 8, 16, 24 and 48 h post inoculation. Comprehensive analysis of ECM-associated proteins was performed by extracting wall-bound and soluble ECM components using both destructive and non-destructive procedures. A total of 53 proteins was differentially expressed in citrus-Xanthomonas host and non-host interaction, out of which 44 were identified by mass spectrometry. The differentially expressed proteins were related to (1) defense-response (5 pathogenesis-related proteins, 3 miraculin-like proteins (MIR, MIR1 and MIR2) and 2 proteases); (2) enzymes of reactive oxygen species (ROS) metabolism [Cu/Zn superoxide dismutase (SOD), Fe-SOD, ascorbate peroxidase and 2-cysteine-peroxiredoxin]; (3) signaling (lectin, curculin-like lectin and concanavalin A-like lectin kinase); and (4) cell-wall modification (α-xylosidase, glucan 1, 3 β-glucosidase, xyloglucan endotransglucosylase/hydrolase). The decrease in ascorbate peroxidase and cysteine-peroxiredoxin could be involved in maintenance of ROS levels. Increase in defense, cell-wall remodeling and signaling proteins in citrus-Xoo interaction suggests an active involvement of ECM in execution of NHR. Partially compromised NHR in citrus against Xoo, upon Brefeldin A pre-treatment supported the role of non-classical secretory proteins in this phenomenon. © 2013 Scandinavian Plant Physiology Society.

Gene Expression Profiling of Monkeypox Virus-Infected Cells Reveals Novel Interfaces for Host-Virus Interactions

DTIC Science & Technology

2010-07-28

expression is plotted on Y -axis after normalization to mock-treated samples. Results plotted to compare calculated fold change in expression of each gene ...RESEARCH Open Access Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions Abdulnaser...suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes

The interaction of gut microbes with host ABC transporters

PubMed Central

Mercado-Lubo, Regino

2010-01-01

ATP binding cassette (ABC) transporters are increasingly recognized for their ability to modulate the absorption, distribution, metabolism, secretion and toxicity of xenobiotics. In addition to their essential function in drug resistance, there is also emerging evidence documenting the important role ABC transporters play in tissue defense. In this respect, the gastrointestinal tract represents a critical vanguard of defense against oral exposure of drugs while at the same time functions as a physical barrier between the lumenal contents (including bacteria) and the intestinal epithelium. Given emerging evidence suggesting that multidrug resistance protein (MDR) plays an important role in host-bacterial interactions in the gastrointestinal tract, this review will discuss the interplay between MDR of the intestinal epithelial cell barrier and gut microbes in health and disease. In particular, we will explore host-microbe interactions involving three apically restricted ABC transporters of the intestinal epithelium; P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and cystic fibrosis transmembrane regulator (CFTR). PMID:21327038

Host and bacterial factors that regulate LC3 recruitment to Listeria monocytogenes during the early stages of macrophage infection.

PubMed

Lam, Grace Y; Cemma, Marija; Muise, Aleixo M; Higgins, Darren E; Brumell, John H

2013-07-01

Listeria monocytogenes is a bacterial pathogen that can escape the phagosome and replicate in the cytosol of host cells during infection. We previously observed that a population (up to 35%) of L. monocytogenes strain 10403S colocalize with the macroautophagy marker LC3 at 1 h postinfection. This is thought to give rise to spacious Listeria-containing phagosomes (SLAPs), a membrane-bound compartment harboring slow-growing bacteria that is associated with persistent infection. Here, we examined the host and bacterial factors that mediate LC3 recruitment to bacteria at 1 h postinfection. At this early time point, LC3(+) bacteria were present within single-membrane phagosomes that are LAMP1(+). Protein ubiquitination is known to play a role in targeting cytosolic L. monocytogenes to macroautophagy. However, we found that neither protein ubiquitination nor the ubiquitin-binding adaptor SQSTM1/p62 are associated with LC3(+) bacteria at 1 h postinfection. Reactive oxygen species (ROS) production by the CYBB/NOX2 NADPH oxidase was also required for LC3 recruitment to bacteria at 1 h postinfection and for subsequent SLAP formation. Diacylglycerol is an upstream activator of the CYBB/NOX2 NADPH oxidase, and its production by both bacterial and host phospholipases was required for LC3 recruitment to bacteria. Our data suggest that the LC3-associated phagocytosis (LAP) pathway, which is distinct from macroautophagy, targets L. monocytogenes during the early stage of infection within host macrophages and allows establishment of an intracellular niche (SLAPs) associated with persistent infection.

Maternal androgens in avian brood parasites and their hosts: responses to parasitism and competition?

USGS Publications Warehouse

Hahn, Caldwell; Wingfield, John C.; Fox, David M.; Walker, Brian G.; Thomley, Jill E

2017-01-01

In the coevolutionary dynamic of avian brood parasites and their hosts, maternal (or transgenerational) effects have rarely been investigated. We examined the potential role of elevated yolk testosterone in eggs of the principal brood parasite in North America, the brown-headed cowbird, and three of its frequent host species. Elevated maternal androgens in eggs are a common maternal effect observed in many avian species when breeding conditions are unfavorable. These steroids accelerate embryo development, shorten incubation period, increase nestling growth rate, and enhance begging vigor, all traits that can increase the survival of offspring. We hypothesized that elevated maternal androgens in host eggs are a defense against brood parasitism. Our second hypothesis was that elevated maternal androgens in cowbird eggs are a defense against intra-specific competition. For host species, we found that elevated yolk testosterone was correlated with parasitized nests of small species, those whose nest success is most reduced by cowbird parasitism. For cowbirds, we found that elevated yolk testosterone was correlated with eggs in multiply-parasitized nests, which indicate intra-specific competition for nests due to high cowbird density. We propose experimental work to further examine the use of maternal effects by cowbirds and their hosts.

Plant defenses against parasitic plants show similarities to those induced by herbivores and pathogens

PubMed Central

Runyon, Justin B; Mescher, Mark C

2010-01-01

Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling and response to herbivores and pathogens has expanded rapidly in recent years, but information is generally lacking for parasitic species. In a recent paper we reported that some of the same defense responses induced by herbivores and pathogens—notably increases in jasmonic acid (JA), salicylic acid (SA), and a hypersensitive-like response (HLR)—also occur in tomato plants upon attack by the parasitic plant Cuscuta pentagona (field dodder). Parasitism induced a distinct pattern of JA and SA accumulation, and growth trials using genetically-altered tomato hosts suggested that both JA and SA govern effective defenses against the parasite, though the extent of the response varied with host plant age. Here we discuss similarities between the induced responses we observed in response to Cuscuta parasitism to those previously described for herbivores and pathogens and present new data showing that trichomes should be added to the list of plant defenses that act against multiple enemies and across kingdoms. PMID:20495380

Plant defenses against parasitic plants show similarities to those induced by herbivores and pathogens.

PubMed

Runyon, Justin B; Mescher, Mark C; De Moraes, Consuelo M

2010-08-01

Herbivores and pathogens come quickly to mind when one thinks of the biotic challenges faced by plants. Important but less appreciated enemies are parasitic plants, which can have important consequences for the fitness and survival of their hosts. Our knowledge of plant perception, signaling, and response to herbivores and pathogens has expanded rapidly in recent years, but information is generally lacking for parasitic species. In a recent paper we reported that some of the same defense responses induced by herbivores and pathogens--notably increases in jasmonic acid (JA), salicylic acid (SA), and a hypersensitive-like response (HLR)--also occur in tomato plants upon attack by the parasitic plant Cuscuta pentagona (field dodder). Parasitism induced a distinct pattern of JA and SA accumulation, and growth trials using genetically-altered tomato hosts suggested that both JA and SA govern effective defenses against the parasite, though the extent of the response varied with host plant age. Here we discuss similarities between the induced responses we observed in response to Cuscuta parasitism to those previously described for herbivores and pathogens and present new data showing that trichomes should be added to the list of plant defenses that act against multiple enemies and across Kingdoms.

Defensive behaviors of the Oriental armyworm Mythimna separata in response to different parasitoid species (Hymenoptera: Braconidae).

PubMed

Zhou, Jincheng; Meng, Ling; Li, Baoping

2017-01-01

This study examined defensive behaviors of Mythimna separata (Lepidoptera: Noctuidae) larvae varying in body size in response to two parasitoids varying in oviposition behavior; Microplitis mediator females sting the host with the ovipositor after climbing onto it while Meteorus pulchricornis females make the sting by standing at a close distance from the host. Mythimna separata larvae exhibited evasive (escaping and dropping) and aggressive (thrashing) behaviors to defend themselves against parasitoids M. mediator and M. pulchricornis . Escaping and dropping did not change in probability with host body size or parasitoid species. Thrashing did not vary in frequency with host body size, yet performed more frequently in response to M. mediator than to M. pulchricornis . Parasitoid handling time and stinging likelihood varied depending not only on host body size but also on parasitoid species. Parasitoid handling time increased with host thrashing frequency, similar in slope for both parasitoids yet on a higher intercept for M. mediator than for M. pulchricornis . Handling time decreased with host size for M. pulchricornis but not for M. mediator . The likelihood of realizing an ovipositor sting decreased with thrashing frequency of both small and large hosts for M. pulchricornis , while this was true only for large hosts for M. mediator . Our results suggest that the thrashing behavior of M. separata larvae has a defensive effect on parasitism, depending on host body size and parasitoid species with different oviposition behaviors.

Defensive behaviors of the Oriental armyworm Mythimna separata in response to different parasitoid species (Hymenoptera: Braconidae)

PubMed Central

Zhou, Jincheng; Meng, Ling

2017-01-01

This study examined defensive behaviors of Mythimna separata (Lepidoptera: Noctuidae) larvae varying in body size in response to two parasitoids varying in oviposition behavior; Microplitis mediator females sting the host with the ovipositor after climbing onto it while Meteorus pulchricornis females make the sting by standing at a close distance from the host. Mythimna separata larvae exhibited evasive (escaping and dropping) and aggressive (thrashing) behaviors to defend themselves against parasitoids M. mediator and M. pulchricornis. Escaping and dropping did not change in probability with host body size or parasitoid species. Thrashing did not vary in frequency with host body size, yet performed more frequently in response to M. mediator than to M. pulchricornis. Parasitoid handling time and stinging likelihood varied depending not only on host body size but also on parasitoid species. Parasitoid handling time increased with host thrashing frequency, similar in slope for both parasitoids yet on a higher intercept for M. mediator than for M. pulchricornis. Handling time decreased with host size for M. pulchricornis but not for M. mediator. The likelihood of realizing an ovipositor sting decreased with thrashing frequency of both small and large hosts for M. pulchricornis, while this was true only for large hosts for M. mediator. Our results suggest that the thrashing behavior of M. separata larvae has a defensive effect on parasitism, depending on host body size and parasitoid species with different oviposition behaviors. PMID:28852593

Limiting the cost of mutualism: the defensive role of elongated gynophore in the leafflower-moth mutualism.

PubMed

Furukawa, Saori; Kawakita, Atsushi

2017-08-01

Mutualisms are interactions from which both partners benefit but may collapse if mutualists' costs and benefits are not aligned. Host sanctions are one mechanism whereby hosts selectively allocate resources to the more cooperative partners and thereby reduce the fitness of overexploiters; however, many mutualisms lack apparent means of host sanctions. In mutualisms between plants and pollinating seed parasites, such as those between leafflowers and leafflower moths, pollinators consume subsets of the seeds as larval food in return for their pollination service. Plants may select against overexploiters by selectively aborting flowers with a heavy egg load, but in many leafflower species, seeds are fully eaten in some fruits, suggesting that such a mechanism is not present in all species. Instead, the fruits of Breynia vitis-idaea have stalk-like structures (gynophore) through which early-instar moth larvae must bore to reach seeds. Examination of moth mortality in fruits with different gynophore lengths suggested that fruits with longer gynophore had higher moth mortality and, therefore, less seed damage. Most moth mortality occurred at the egg stage or as early larval instar before moths reached the seeds, consistent with the view that gynophore functions to prevent moth access to seeds. Gynophore length was unaffected by plant size, extent of moth oviposition, or geography; thus, it is most likely genetically controlled. Because gynophores do not elongate in related species whose pollinators oviposit directly into the ovary, the gynophore in B. vitis-idaea may have evolved as a defense to limit the cost of the mutualism.

Characterizing the proteome and oxi-proteome of apple in response to a host (Penicillium expansum) and a non-host (Penicillium digitatum) pathogen.

PubMed

Buron-Moles, Gemma; Wisniewski, Michael; Viñas, Inmaculada; Teixidó, Neus; Usall, Josep; Droby, Samir; Torres, Rosario

2015-01-30

Apples are subjected to both abiotic and biotic stresses during the postharvest period, which lead to large economic losses worldwide. To obtain biochemical insights into apple defense response, we monitored the protein abundance changes (proteome), as well as the protein carbonyls (oxi-proteome) formed by reactive oxygen species (ROS) in 'Golden Smoothee' apple in response to wounding, Penicillium expansum (host) and Penicillium digitatum (non-host) pathogens with select transcriptional studies. To examine the biological relevance of the results, we described quantitative and oxidative protein changes into the gene ontology functional categories, as well as into de KEGG pathways. We identified 26 proteins that differentially changed in abundance in response to wounding, P. expansum or P. digitatum infection. While these changes showed some similarities between the apple responses and abiotic and biotic stresses, Mal d 1.03A case, other proteins as Mal d 1.03E and EF-Tu were specifically induced in response to P. digitatum infection. Using a protein carbonyl detection method based on fluorescent Bodipy, we detected and identified 27 oxidized proteins as sensitive ROS targets. These ROS target proteins were related to metabolism processes, suggesting that this process plays a leading role in apple fruit defense response against abiotic and biotic stresses. ACC oxidase and two glutamine synthetases showed the highest protein oxidation level in response to P. digitatum infection. Documenting changes in the proteome and, specifically in oxi-proteome of apple can provide information that can be used to better understand how impaired protein functions may affect apple defense mechanisms. Possible mechanisms by which these modified proteins are involved in fruit defense response are discussed. Mechanical damage in apple fruits is linked annually to large economic losses due to opportunistic infection by postharvest pathogens, such as P. expansum. Despite the current use

A Vesicular Arbuscular Mycorrhizal Fungus (Glomus intraradix) Induces a Defense Response in Alfalfa Roots.

PubMed

Volpin, H.; Elkind, Y.; Okon, Y.; Kapulnik, Y.

1994-02-01

Flavonoid accumulation and activities of phenylalanine ammonia-lyase (PAL), chalcone isomerase (CHI), and chitinase were followed during early colonization of alfalfa roots (Medicago sativa L. cv Gilboa) by vesicular arbuscular (VA) fungi (Glomus intraradix). Formononetin was the only flavonoid detected that showed a consistent increase in the inoculated roots. This increase depended only on the presence of the fungus in the plant rhizosphere; no colonization of the root tissue was required. CHI and chitinase activities increased in inoculated roots prior to colonization, whereas the increase in PAL activity coincided with colonization. After reaching a maximum, activities of all enzymes declined to below those of uninoculated roots. PAL inactivation was not caused by a soluble inhibitor. Our results indicate that VA fungi initiate a host defense response in alfalfa roots, which is subsequently suppressed.

Glucosinolates from Host Plants Influence Growth of the Parasitic Plant Cuscuta gronovii and Its Susceptibility to Aphid Feeding1[OPEN

PubMed Central

2016-01-01

Parasitic plants acquire diverse secondary metabolites from their hosts, including defense compounds that target insect herbivores. However, the ecological implications of this phenomenon, including the potential enhancement of parasite defenses, remain largely unexplored. We studied the translocation of glucosinolates from the brassicaceous host plant Arabidopsis (Arabidopsis thaliana) into parasitic dodder vines (Convolvulaceae; Cuscuta gronovii) and its effects on the parasite itself and on dodder-aphid interactions. Aliphatic and indole glucosinolates reached concentrations in parasite tissues higher than those observed in corresponding host tissues. Dodder growth was enhanced on cyp79B2 cyp79B3 hosts (without indole glucosinolates) but inhibited on atr1D hosts (with elevated indole glucosinolates) relative to wild-type hosts, which responded to parasitism with localized elevation of indole and aliphatic glucosinolates. These findings implicate indole glucosinolates in defense against parasitic plants. Rates of settling and survival on dodder vines by pea aphids (Acyrthosiphon pisum) were reduced significantly when dodder parasitized glucosinolate-producing hosts (wild type and atr1D) compared with glucosinolate-free hosts (cyp79B2 cyp79B3 myb28 myb29). However, settling and survival of green peach aphids (Myzus persicae) were not affected. M. persicae population growth was actually reduced on dodder parasitizing glucosinolate-free hosts compared with wild-type or atr1D hosts, even though stems of the former contain less glucosinolates and more amino acids. Strikingly, this effect was reversed when the aphids fed directly upon Arabidopsis, which indicates an interactive effect of parasite and host genotype on M. persicae that stems from host effects on dodder. Thus, our findings indicate that glucosinolates may have both direct and indirect effects on dodder-feeding herbivores. PMID:27482077

Viral Ubiquitin Ligase Stimulates Selective Host MicroRNA Expression by Targeting ZEB Transcriptional Repressors

PubMed Central

Kim, Ju Youn; Leader, Andrew; Stoller, Michelle L.; Coen, Donald M.; Wilson, Angus C.

2017-01-01

Infection with herpes simplex virus-1 (HSV-1) brings numerous changes in cellular gene expression. Levels of most host mRNAs are reduced, limiting synthesis of host proteins, especially those involved in antiviral defenses. The impact of HSV-1 on host microRNAs (miRNAs), an extensive network of short non-coding RNAs that regulate mRNA stability/translation, remains largely unexplored. Here we show that transcription of the miR-183 cluster (miR-183, miR-96, and miR-182) is selectively induced by HSV-1 during productive infection of primary fibroblasts and neurons. ICP0, a viral E3 ubiquitin ligase expressed as an immediate-early protein, is both necessary and sufficient for this induction. Nuclear exclusion of ICP0 or removal of the RING (really interesting new gene) finger domain that is required for E3 ligase activity prevents induction. ICP0 promotes the degradation of numerous host proteins and for the most part, the downstream consequences are unknown. Induction of the miR-183 cluster can be mimicked by depletion of host transcriptional repressors zinc finger E-box binding homeobox 1 (ZEB1)/δ-crystallin enhancer binding factor 1 (δEF1) and zinc finger E-box binding homeobox 2 (ZEB2)/Smad-interacting protein 1 (SIP1), which we establish as new substrates for ICP0-mediated degradation. Thus, HSV-1 selectively stimulates expression of the miR-183 cluster by ICP0-mediated degradation of ZEB transcriptional repressors. PMID:28783105

Host fish suitability for glochidia of Ligumia recta

USGS Publications Warehouse

Khym, J.R.; Layzer, J.B.

2000-01-01

In the early 1900s several hosts were identified for the black sandshell Ligumia recta. Recent attempts to propagate juvenile L. recta with two of the reported hosts (bluegill Lepomis macrochirus and largemouth bass Micropterus salmoides) have produced inconsistent results and few juveniles. We conducted this study to determine which of the reported hosts or other fish hosts were the most suitable for glochidial metamorphosis. The duration of glochidial metamorphosis varied among seasons. Despite similar water temperatures, juveniles metamorphosed sooner and over a shorter period of time in the spring than early fall; the modal day of metamorphosis differed by 78 d. Relatively few juveniles were recovered from bluegill and largemouth bass in three trials. White crappie Pomoxis annularis and black crappie P. nigromaculatus were marginally suitable hosts. Although glochidia encysted on all hosts, >10x more juveniles metamorphosed on sauger Stizostedion canadense compared to other hosts tested.

Mechanisms of plant defense against insect herbivores

PubMed Central

War, Abdul Rashid; Paulraj, Michael Gabriel; Ahmad, Tariq; Buhroo, Abdul Ahad; Hussain, Barkat; Ignacimuthu, Savarimuthu; Sharma, Hari Chand

2012-01-01

Plants respond to herbivory through various morphological, biochemicals, and molecular mechanisms to counter/offset the effects of herbivore attack. The biochemical mechanisms of defense against the herbivores are wide-ranging, highly dynamic, and are mediated both by direct and indirect defenses. The defensive compounds are either produced constitutively or in response to plant damage, and affect feeding, growth, and survival of herbivores. In addition, plants also release volatile organic compounds that attract the natural enemies of the herbivores. These strategies either act independently or in conjunction with each other. However, our understanding of these defensive mechanisms is still limited. Induced resistance could be exploited as an important tool for the pest management to minimize the amounts of insecticides used for pest control. Host plant resistance to insects, particularly, induced resistance, can also be manipulated with the use of chemical elicitors of secondary metabolites, which confer resistance to insects. By understanding the mechanisms of induced resistance, we can predict the herbivores that are likely to be affected by induced responses. The elicitors of induced responses can be sprayed on crop plants to build up the natural defense system against damage caused by herbivores. The induced responses can also be engineered genetically, so that the defensive compounds are constitutively produced in plants against are challenged by the herbivory. Induced resistance can be exploited for developing crop cultivars, which readily produce the inducible response upon mild infestation, and can act as one of components of integrated pest management for sustainable crop production. PMID:22895106

Host and Bacterial Proteins That Repress Recruitment of LC3 to Shigella Early during Infection

PubMed Central

Baxt, Leigh A.; Goldberg, Marcia B.

2014-01-01

Shigella spp. are intracytosolic gram-negative pathogens that cause disease by invasion and spread through the colonic mucosa, utilizing host cytoskeletal components to form propulsive actin tails. We have previously identified the host factor Toca-1 as being recruited to intracellular S. flexneri and being required for efficient bacterial actin tail formation. We show that at early times during infection (40 min.), the type three-secreted effector protein IcsB recruits Toca-1 to intracellular bacteria and that recruitment of Toca-1 is associated with repression of recruitment of LC3, as well as with repression of recruitment of the autophagy marker NDP52, around these intracellular bacteria. LC3 is best characterized as a marker of autophagosomes, but also marks phagosomal membranes in the process LC3-associated phagocytosis. IcsB has previously been demonstrated to be required for S. flexneri evasion of autophagy at late times during infection (4–6 hr) by inhibiting binding of the autophagy protein Atg5 to the Shigella surface protein IcsA (VirG). Our results suggest that IcsB and Toca-1 modulation of LC3 recruitment restricts LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants. Together with published results, our findings suggest that IcsB inhibits innate immune responses in two distinct ways, first, by inhibiting LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants early during infection, and second, by inhibiting autophagy late during infection. PMID:24722587

Reconstruction of the evolution of microbial defense systems.

PubMed

Puigbò, Pere; Makarova, Kira S; Kristensen, David M; Wolf, Yuri I; Koonin, Eugene V

2017-04-04

Evolution of bacterial and archaeal genomes is a highly dynamic process that involves intensive loss of genes as well as gene gain via horizontal transfer, with a lesser contribution from gene duplication. The rates of these processes can be estimated by comparing genomes that are linked by an evolutionary tree. These estimated rates of genome dynamics events substantially differ for different functional classes of genes. The genes involved in defense against viruses and other invading DNA are among those that are gained and lost at the highest rates. We employed a stochastic birth-and-death model to obtain maximum likelihood estimates of the rates of gain and loss of defense genes in 35 groups of closely related bacterial genomes and one group of archaeal genomes. We find that on average, the defense genes experience 1.4 fold higher flux than the rest of microbial genes. This excessive flux of defense genes over the genomic mean is consistent across diverse microbial groups. The few exceptions include intracellular parasites with small, degraded genomes that possess few defense systems which are more stable than in other microbes. Generally, defense genes follow the previously established pattern of genome dynamics, with gene family loss being about 3 times more common than gain and an order of magnitude more common than expansion or contraction of gene families. Case by case analysis of the evolutionary dynamics of defense genes indicates frequent multiple events in the same locus and widespread involvement of mobile elements in the gain and loss of defense genes. Evolution of microbial defense systems is highly dynamic but, notwithstanding the host-parasite arms race, generally follows the same trends that have been established for the rest of the genes. Apart from the paucity and the low flux of defense genes in parasitic bacteria with deteriorating genomes, there is no clear connection between the evolutionary regime of defense systems and microbial life style.

Do host species evolve a specific response to slave-making ants?

PubMed Central

2012-01-01

Background Social parasitism is an important selective pressure for social insect species. It is particularly the case for the hosts of dulotic (so called slave-making) ants, which pillage the brood of host colonies to increase the worker force of their own colony. Such raids can have an important impact on the fitness of the host nest. An arms race which can lead to geographic variation in host defenses is thus expected between hosts and parasites. In this study we tested whether the presence of a social parasite (the dulotic ant Myrmoxenus ravouxi) within an ant community correlated with a specific behavioral defense strategy of local host or non-host populations of Temnothorax ants. Social recognition often leads to more or less pronounced agonistic interactions between non-nestmates ants. Here, we monitored agonistic behaviors to assess whether ants discriminate social parasites from other ants. It is now well-known that ants essentially rely on cuticular hydrocarbons to discriminate nestmates from aliens. If host species have evolved a specific recognition mechanism for their parasite, we hypothesize that the differences in behavioral responses would not be fully explained simply by quantitative dissimilarity in cuticular hydrocarbon profiles, but should also involve a qualitative response due to the detection of particular compounds. We scaled the behavioral results according to the quantitative chemical distance between host and parasite colonies to test this hypothesis. Results Cuticular hydrocarbon profiles were distinct between species, but host species did not show a clearly higher aggression rate towards the parasite than toward non-parasite intruders, unless the degree of response was scaled by the chemical distance between intruders and recipient colonies. By doing so, we show that workers of the host and of a non-host species in the parasitized site displayed more agonistic behaviors (bites and ejections) towards parasite than toward non

An evolutionary missing link? A modest-mass early-type galaxy hosting an oversized nuclear black hole

NASA Astrophysics Data System (ADS)

van Loon, Jacco Th.; Sansom, Anne E.

2015-11-01

SAGE1C J053634.78-722658.5 is a galaxy at redshift z = 0.14, discovered behind the Large Magellanic Cloud in the Spitzer Space Telescope`Surveying the Agents of Galaxy Evolution' Spectroscopy survey. It has very strong silicate emission at 10 μm but negligible far-IR and UV emission. This makes it a candidate for a bare active galactic nuclei (AGN) source in the IR, perhaps seen pole-on, without significant IR emission from the host galaxy. In this paper we present optical spectra taken with the Southern African Large Telescope to investigate the nature of the underlying host galaxy and its AGN. We find broad H α emission characteristic of an AGN, plus absorption lines associated with a mature stellar population (>9 Gyr), and refine its redshift determination to z = 0.1428 ± 0.0001. There is no evidence for any emission lines associated with star formation. This remarkable object exemplifies the need for separating the emission from any AGN from that of the host galaxy when employing IR diagnostic diagrams. We estimate the black hole mass, MBH = 3.5 ± 0.8 × 108 M⊙, host galaxy mass, M_stars=2.5^{2.5}_{1.2}× 10^{10} M⊙, and accretion luminosity, Lbol(AGN) = 5.3 ± 0.4 × 1045 erg s-1 (≈12 per cent of the Eddington luminosity), and find the AGN to be more prominent than expected for a host galaxy of this modest size. The old age is in tension with the downsizing paradigm in which this galaxy would recently have transformed from a star-forming disc galaxy into an early-type, passively evolving galaxy.

Immune defense in leaf-cutting ants: a cross-fostering approach.

PubMed

Armitage, Sophie A O; Broch, Jens F; Marín, Hermogenes Fernández; Nash, David R; Boomsma, Jacobus J

2011-06-01

To ameliorate the impact of disease, social insects combine individual innate immune defenses with collective social defenses. This implies that there are different levels of selection acting on investment in immunity, each with their own trade-offs. We present the results of a cross-fostering experiment designed to address the influences of genotype and social rearing environment upon individual and social immune defenses. We used a multiply mating leaf-cutting ant, enabling us to test for patriline effects within a colony, as well as cross-colony matriline effects. The worker's father influenced both individual innate immunity (constitutive antibacterial activity) and the size of the metapleural gland, which secretes antimicrobial compounds and functions in individual and social defense, indicating multiple mating could have important consequences for both defense types. However, the primarily social defense, a Pseudonocardia bacteria that helps to control pathogens in the ants' fungus garden, showed a significant colony of origin by rearing environment interaction, whereby ants that acquired the bacteria of a foster colony obtained a less abundant cover of bacteria: one explanation for this pattern would be co-adaptation between host colonies and their vertically transmitted mutualist. These results illustrate the complexity of the selection pressures that affect the expression of multilevel immune defenses. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms

PubMed Central

Warren, Kristi J.; Olson, Molly M.; Thompson, Nicholas J.; Cahill, Mackenzie L.; Wyatt, Todd A.; Yoon, Kyoungjin J.; Loiacono, Christina M.; Kohut, Marian L.

2015-01-01

Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise “restores” the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response. PMID:26110868

Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

PubMed Central

Das, Rina; Hammamieh, Rasha; Neill, Roger; Ludwig, George V; Eker, Steven; Lincoln, Patrick; Ramamoorthy, Preveen; Dhokalia, Apsara; Mani, Sachin; Mendis, Chanaka; Cummings, Christiano; Kearney, Brian; Royaee, Atabak; Huang, Xiao-Zhe; Paranavitana, Chrysanthi; Smith, Leonard; Peel, Sheila; Kanesa-Thasan, Niranjan; Hoover, David; Lindler, Luther E; Yang, David; Henchal, Erik; Jett, Marti

2008-01-01

Background Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs. Methods To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays. Results We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin. Conclusion Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents. PMID:18667072

Sequestration of host metabolism by an intracellular pathogen.

PubMed

Gehre, Lena; Gorgette, Olivier; Perrinet, Stéphanie; Prevost, Marie-Christine; Ducatez, Mathieu; Giebel, Amanda M; Nelson, David E; Ball, Steven G; Subtil, Agathe

2016-03-16

For intracellular pathogens, residence in a vacuole provides a shelter against cytosolic host defense to the cost of limited access to nutrients. The human pathogen Chlamydia trachomatis grows in a glycogen-rich vacuole. How this large polymer accumulates there is unknown. We reveal that host glycogen stores shift to the vacuole through two pathways: bulk uptake from the cytoplasmic pool, and de novo synthesis. We provide evidence that bacterial glycogen metabolism enzymes are secreted into the vacuole lumen through type 3 secretion. Our data bring strong support to the following scenario: bacteria co-opt the host transporter SLC35D2 to import UDP-glucose into the vacuole, where it serves as substrate for de novo glycogen synthesis, through a remarkable adaptation of the bacterial glycogen synthase. Based on these findings we propose that parasitophorous vacuoles not only offer protection but also provide a microorganism-controlled metabolically active compartment essential for redirecting host resources to the pathogens.

TREM-1 signaling promotes host defense during the early stage of infection with highly pathogenic Streptococcus suis.

PubMed

Yang, Chao; Chen, Bo; Zhao, Jianqing; Lin, Lan; Han, Li; Pan, Shan; Fu, Lei; Jin, Meilin; Chen, Huanchun; Zhang, Anding

2015-08-01

Infection with highly pathogenic Streptococcus suis can cause septic shock, which is characterized by high levels of inflammatory cytokines and a high mortality rate. Our previous study indicated that TREM-1 (triggering receptor expressed on myeloid cells 1) was upregulated in swine spleen cells in response to S. suis infection. The role of TREM-1 signaling in enhancement of the proinflammatory response promoted us to examine its effect on the outcome of S. suis infection. In the present study, the recombinant extracellular domain of TREM-1 (rTREM-1) and an agonistic TREM-1 antibody were used to inhibit and activate TREM-1 signaling to evaluate its role in neutrophil activation, pathogen clearance, proinflammatory cytokine response, and the outcome of highly pathogenic S. suis infection in a mouse model. Blockage of TREM-1 signaling caused a more severe proinflammatory response to S. suis infection and increased the mortality rate, while its activation had the opposite effect. Blockage or activation of TREM-1 signaling lowered or raised the number of neutrophils in the blood, which correlated well with host clearance of S. suis. In conclusion, the TREM-1-mediated innate immune response played an essential role in the activation of neutrophils and S. suis clearance, which further reduced severe inflammation and finally benefited the outcome of the infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Expression of host defense peptides in the intestine of Eimeria-challenged chickens.

PubMed

Su, S; Dwyer, D M; Miska, K B; Fetterer, R H; Jenkins, M C; Wong, E A

2017-07-01

Avian coccidiosis is caused by the intracellular protozoan Eimeria, which produces intestinal lesions leading to weight gain depression. Current control methods include vaccination and anticoccidial drugs. An alternative approach involves modulating the immune system. The objective of this study was to profile the expression of host defense peptides such as avian beta-defensins (AvBDs) and liver expressed antimicrobial peptide 2 (LEAP2), which are part of the innate immune system. The mRNA expression of AvBD family members 1, 6, 8, 10, 11, 12, and 13 and LEAP2 was examined in chickens challenged with either E. acervulina, E. maxima, or E. tenella. The duodenum, jejunum, ileum, and ceca were collected 7 d post challenge. In study 1, E. acervulina challenge resulted in down-regulation of AvBD1, AvBD6, AvBD10, AvBD11, AvBD12, and AvBD13 in the duodenum. E. maxima challenge caused down-regulation of AvBD6, AvBD10, and AvBD11 in the duodenum, down-regulation of AvBD10 in the jejunum, but up-regulation of AvBD8 and AvBD13 in the ceca. E. tenella challenge showed no change in AvBD expression in any tissue. In study 2, which involved challenge with only E. maxima, there was down-regulation of AvBD1 in the ileum, AvBD11 in the jejunum and ileum, and LEAP2 in all 3 segments of the small intestine. The expression of LEAP2 was further examined by in situ hybridization in the jejunum of chickens from study 2. LEAP2 mRNA was expressed similarly in the enterocytes lining the villi, but not in the crypts of control and Eimeria challenged chickens. The lengths of the villi in the Eimeria challenged chickens were less than those in the control chickens, which may in part account for the observed down-regulation of LEAP2 mRNA quantified by PCR. Overall, the AvBD response to Eimeria challenge was not consistent; whereas LEAP2 was consistently down-regulated, which suggests that LEAP2 plays an important role in modulating an Eimeria infection. Published by Oxford University Press on

Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission.

PubMed

Rao, Sheila; Schieber, Alexandria M Palaferri; O'Connor, Carolyn P; Leblanc, Mathias; Michel, Daniela; Ayres, Janelle S

2017-01-26

Sickness-induced anorexia is a conserved behavior induced during infections. Here, we report that an intestinal pathogen, Salmonella Typhimurium, inhibits anorexia by manipulating the gut-brain axis. Inhibition of inflammasome activation by the S. Typhimurium effector, SlrP, prevented anorexia caused by IL-1β-mediated signaling to the hypothalamus via the vagus nerve. Rather than compromising host defenses, pathogen-mediated inhibition of anorexia increased host survival. SlrP-mediated inhibition of anorexia prevented invasion and systemic infection by wild-type S. Typhimurium, reducing virulence while increasing transmission to new hosts, suggesting that there are trade-offs between transmission and virulence. These results clarify the complex and contextual role of anorexia in host-pathogen interactions and suggest that microbes have evolved mechanisms to modulate sickness-induced behaviors to promote health of their host and their transmission at the expense of virulence. Copyright © 2017 Elsevier Inc. All rights reserved.

Bacterial effectors target the plant cell nucleus to subvert host transcription.

PubMed

Canonne, Joanne; Rivas, Susana

2012-02-01

In order to promote virulence, Gram-negative bacteria have evolved the ability to inject so-called type III effector proteins into host cells. The plant cell nucleus appears to be a subcellular compartment repeatedly targeted by bacterial effectors. In agreement with this observation, mounting evidence suggests that manipulation of host transcription is a major strategy developed by bacteria to counteract plant defense responses. It has been suggested that bacterial effectors may adopt at least three alternative, although not mutually exclusive, strategies to subvert host transcription. T3Es may (1) act as transcription factors that directly activate transcription in host cells, (2) affect histone packing and chromatin configuration, and/or (3) target host transcription factor activity. Here, we provide an overview on how all these strategies may lead to host transcriptional re-programming and, as a result, to improved bacterial multiplication inside plant cells.

Key role for scavenger receptor B-I in the integrative physiology of host defense during bacterial pneumonia.

PubMed

Gowdy, K M; Madenspacher, J H; Azzam, K M; Gabor, K A; Janardhan, K S; Aloor, J J; Fessler, M B

2015-05-01

Scavenger receptor B-I (SR-BI) is a multirecognition receptor that regulates cholesterol trafficking and cardiovascular inflammation. Although it is expressed by neutrophils (PMNs) and lung-resident cells, no role for SR-BI has been defined in pulmonary immunity. Herein, we report that, compared with SR-BI(+/+) counterparts, SR-BI(-/-) mice suffer markedly increased mortality during bacterial pneumonia associated with higher bacterial burden in the lung and blood, deficient induction of the stress glucocorticoid corticosterone, higher serum cytokines, and increased organ injury. SR-BI(-/-) mice had significantly increased PMN recruitment and cytokine production in the infected airspace. This was associated with defective hematopoietic cell-dependent clearance of lipopolysaccharide from the airspace and increased cytokine production by SR-BI(-/-) macrophages. Corticosterone replacement normalized alveolar neutrophilia but not alveolar cytokines, bacterial burden, or mortality, suggesting that adrenal insufficiency derepresses PMN trafficking to the SR-BI(-/-) airway in a cytokine-independent manner. Despite enhanced alveolar neutrophilia, SR-BI(-/-) mice displayed impaired phagocytic killing. Bone marrow chimeras revealed this defect to be independent of the dyslipidemia and adrenal insufficiency of SR-BI(-/-) mice. During infection, SR-BI(-/-) PMNs displayed deficient oxidant production and CD11b externalization, and increased surface L-selectin, suggesting defective activation. Taken together, SR-BI coordinates several steps in the integrated neutrophilic host defense response to pneumonia.

Change in Coping and Defense Mechanisms across Adulthood: Longitudinal Findings in a European-American Sample

PubMed Central

Diehl, Manfred; Chui, Helena; Hay, Elizabeth L.; Lumley, Mark A.; Grühn, Daniel; Labouvie-Vief, Gisela

2014-01-01

This study examined longitudinal changes in coping and defense mechanisms in an age- and gender-stratified sample of 392 European-American adults. Nonlinear age-related changes were found for the coping mechanisms of sublimation and suppression and the defense mechanisms of intellectualization, doubt, displacement, and regression. The change trajectories for sublimation and suppression showed that their use increased from adolescence to late middle age and early old age, and remained mostly stable into late old age. The change trajectory for intellectualization showed that the use of this defense mechanism increased from adolescence to middle age, remained stable until late midlife, and started to decline thereafter. The defense mechanisms of doubt, displacement, and regression showed decreases from adolescence until early old age, with increases occurring again after the age of 65. Linear age-related decreases were found for the coping mechanism of ego regression and the defense mechanisms of isolation and rationalization. Gender and socioeconomic status were associated with the mean levels of several coping and defense mechanisms, but did not moderate age-related changes. Increases in ego level were associated with increased use of the defense mechanism intellectualization and decreased use of the defense mechanisms of doubt and displacement. Overall, these findings in a European-American sample suggest that most individuals showed development in the direction of more adaptive and less maladaptive coping and defense strategies from adolescence until late middle age or early old age. However, in late old age this development was reversed, presenting potential challenges to the adaptive capacity of older adults. PMID:23834293

Genomic analysis of cold-active Colwelliaphage 9A and psychrophilic phage-host interactions.

PubMed

Colangelo-Lillis, Jesse R; Deming, Jody W

2013-01-01

The 104 kb genome of cold-active bacteriophage 9A, which replicates in the marine psychrophilic gamma-proteobacterium Colwellia psychrerythraea strain 34H (between -12 and 8 °C), was sequenced and analyzed to investigate elements of molecular adaptation to low temperature and phage-host interactions in the cold. Most characterized ORFs indicated closest similarity to gamma-proteobacteria and their phages, though no single module provided definitive phylogenetic grouping. A subset of primary structural features linked to psychrophily suggested that the majority of annotated phage proteins were not psychrophilic; those that were, primarily serve phage-specific functions and may also contribute to 9A's restricted temperature range for replication as compared to host. Comparative analyses suggest ribonucleotide reductase genes were acquired laterally from host. Neither restriction modification nor the CRISPR-Cas system appeared to be the predominant phage defense mechanism of Cp34H or other cold-adapted bacteria; we hypothesize that psychrophilic hosts rely more on the use of extracellular polymeric material to block cell surface receptors recognized by phages. The relative dearth of evidence for genome-specific defenses, genetic transfer events or auxiliary metabolic genes suggest that the 9A-Cp34H system may be less tightly coupled than are other genomically characterized marine phage-host systems, with possible implications for phage specificity under different environmental conditions.

CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy.

PubMed

Chen, Shuliang; Yu, Xiao; Guo, Deyin

2018-01-16

Currently, a new gene editing tool-the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system-is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy.

CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy

PubMed Central

Chen, Shuliang; Yu, Xiao; Guo, Deyin

2018-01-01

Currently, a new gene editing tool—the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) associated (Cas) system—is becoming a promising approach for genetic manipulation at the genomic level. This simple method, originating from the adaptive immune defense system in prokaryotes, has been developed and applied to antiviral research in humans. Based on the characteristics of virus-host interactions and the basic rules of nucleic acid cleavage or gene activation of the CRISPR-Cas system, it can be used to target both the virus genome and host factors to clear viral reservoirs and prohibit virus infection or replication. Here, we summarize recent progress of the CRISPR-Cas technology in editing host genes as an antiviral strategy. PMID:29337866

Costs of immune responses are related to host body size and lifespan

DOE PAGES

Brace, Amber J.; Lajeunesse, Marc J.; Ardia, Daniel R.; ...

2017-06-01

A central assumption in ecological immunology is that immune responses are costly, with costs manifesting directly (e.g., increases in metabolic rate and increased amino acid usage) or as tradeoffs with other life processes (e.g., reduced growth and reproductive success). Across taxa, host longevity, timing of maturity, and reproductive effort affect the organization of immune systems. It is reasonable, therefore, to expect that these and related factors should also affect immune activation costs. Specifically, species that spread their breeding efforts over a long lifetime should experience lower immune costs than those that mature and breed quickly and die comparatively early. Likewise,more » body mass should affect immune costs, as body size affects the extent to which hosts are exposed to parasites as well as how hosts can combat infections (via its effects on metabolic rates and other factors). Here in this paper, we used phylogenetic meta-regression to reveal that, in general, animals incur costs of immune activation, but small species that are relatively long-lived incur the largest costs. These patterns probably arise because of the relative need for defense when infection risk is comparatively high and fitness can only be realized over a comparatively long period. However, given the diversity of species considered here and the overall modest effects of body mass and life history on immune costs, much more research is necessary before generalizations are appropriate.« less

Costs of immune responses are related to host body size and lifespan

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

Brace, Amber J.; Lajeunesse, Marc J.; Ardia, Daniel R.

A central assumption in ecological immunology is that immune responses are costly, with costs manifesting directly (e.g., increases in metabolic rate and increased amino acid usage) or as tradeoffs with other life processes (e.g., reduced growth and reproductive success). Across taxa, host longevity, timing of maturity, and reproductive effort affect the organization of immune systems. It is reasonable, therefore, to expect that these and related factors should also affect immune activation costs. Specifically, species that spread their breeding efforts over a long lifetime should experience lower immune costs than those that mature and breed quickly and die comparatively early. Likewise,more » body mass should affect immune costs, as body size affects the extent to which hosts are exposed to parasites as well as how hosts can combat infections (via its effects on metabolic rates and other factors). Here in this paper, we used phylogenetic meta-regression to reveal that, in general, animals incur costs of immune activation, but small species that are relatively long-lived incur the largest costs. These patterns probably arise because of the relative need for defense when infection risk is comparatively high and fitness can only be realized over a comparatively long period. However, given the diversity of species considered here and the overall modest effects of body mass and life history on immune costs, much more research is necessary before generalizations are appropriate.« less

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.

Defense.gov Special Report: Defense Intelligence

Science.gov Websites

Department of Defense Submit Search Defense intelligence is critical to the Defense Department's role in and conduct successful military and security operations that protect America. Defense Intelligence News Story Intelligence Chief Describes 'Pervasive Uncertainty' of Worldwide Threats "

RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense.

PubMed

Moelling, Karin; Broecker, Felix; Russo, Giancarlo; Sunagawa, Shinichi

2017-01-01

Retroviral infections are 'mini-symbiotic' events supplying recipient cells with sequences for viral replication, including the reverse transcriptase (RT) and ribonuclease H (RNase H). These proteins and other viral or cellular sequences can provide novel cellular functions including immune defense mechanisms. Their high error rate renders RT-RNases H drivers of evolutionary innovation. Integrated retroviruses and the related transposable elements (TEs) have existed for at least 150 million years, constitute up to 80% of eukaryotic genomes and are also present in prokaryotes. Endogenous retroviruses regulate host genes, have provided novel genes including the syncytins that mediate maternal-fetal immune tolerance and can be experimentally rendered infectious again. The RT and the RNase H are among the most ancient and abundant protein folds. RNases H may have evolved from ribozymes, related to viroids, early in the RNA world, forming ribosomes, RNA replicases and polymerases. Basic RNA-binding peptides enhance ribozyme catalysis. RT and ribozymes or RNases H are present today in bacterial group II introns, the precedents of TEs. Thousands of unique RTs and RNases H are present in eukaryotes, bacteria, and viruses. These enzymes mediate viral and cellular replication and antiviral defense in eukaryotes and prokaryotes, splicing, R-loop resolvation, DNA repair. RNase H-like activities are also required for the activity of small regulatory RNAs. The retroviral replication components share striking similarities with the RNA-induced silencing complex (RISC), the prokaryotic CRISPR-Cas machinery, eukaryotic V(D)J recombination and interferon systems. Viruses supply antiviral defense tools to cellular organisms. TEs are the evolutionary origin of siRNA and miRNA genes that, through RISC, counteract detrimental activities of TEs and chromosomal instability. Moreover, piRNAs, implicated in transgenerational inheritance, suppress TEs in germ cells. Thus, virtually all known

RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense

PubMed Central

Moelling, Karin; Broecker, Felix; Russo, Giancarlo; Sunagawa, Shinichi

2017-01-01

Retroviral infections are ‘mini-symbiotic’ events supplying recipient cells with sequences for viral replication, including the reverse transcriptase (RT) and ribonuclease H (RNase H). These proteins and other viral or cellular sequences can provide novel cellular functions including immune defense mechanisms. Their high error rate renders RT-RNases H drivers of evolutionary innovation. Integrated retroviruses and the related transposable elements (TEs) have existed for at least 150 million years, constitute up to 80% of eukaryotic genomes and are also present in prokaryotes. Endogenous retroviruses regulate host genes, have provided novel genes including the syncytins that mediate maternal-fetal immune tolerance and can be experimentally rendered infectious again. The RT and the RNase H are among the most ancient and abundant protein folds. RNases H may have evolved from ribozymes, related to viroids, early in the RNA world, forming ribosomes, RNA replicases and polymerases. Basic RNA-binding peptides enhance ribozyme catalysis. RT and ribozymes or RNases H are present today in bacterial group II introns, the precedents of TEs. Thousands of unique RTs and RNases H are present in eukaryotes, bacteria, and viruses. These enzymes mediate viral and cellular replication and antiviral defense in eukaryotes and prokaryotes, splicing, R-loop resolvation, DNA repair. RNase H-like activities are also required for the activity of small regulatory RNAs. The retroviral replication components share striking similarities with the RNA-induced silencing complex (RISC), the prokaryotic CRISPR-Cas machinery, eukaryotic V(D)J recombination and interferon systems. Viruses supply antiviral defense tools to cellular organisms. TEs are the evolutionary origin of siRNA and miRNA genes that, through RISC, counteract detrimental activities of TEs and chromosomal instability. Moreover, piRNAs, implicated in transgenerational inheritance, suppress TEs in germ cells. Thus, virtually all

Host Diet Affects the Morphology of Monarch Butterfly Parasites.

PubMed

Hoang, Kevin; Tao, Leiling; Hunter, Mark D; de Roode, Jacobus C

2017-06-01

Understanding host-parasite interactions is essential for ecological research, wildlife conservation, and health management. While most studies focus on numerical traits of parasite groups, such as changes in parasite load, less focus is placed on the traits of individual parasites such as parasite size and shape (parasite morphology). Parasite morphology has significant effects on parasite fitness such as initial colonization of hosts, avoidance of host immune defenses, and the availability of resources for parasite replication. As such, understanding factors that affect parasite morphology is important in predicting the consequences of host-parasite interactions. Here, we studied how host diet affected the spore morphology of a protozoan parasite ( Ophryocystis elektroscirrha ), a specialist parasite of the monarch butterfly ( Danaus plexippus ). We found that different host plant species (milkweeds; Asclepias spp.) significantly affected parasite spore size. Previous studies have found that cardenolides, secondary chemicals in host plants of monarchs, can reduce parasite loads and increase the lifespan of infected butterflies. Adding to this benefit of high cardenolide milkweeds, we found that infected monarchs reared on milkweeds of higher cardenolide concentrations yielded smaller parasites, a potentially hidden characteristic of cardenolides that may have important implications for monarch-parasite interactions.

CARD games between virus and host get a new player.

PubMed

Johnson, Cynthia L; Gale, Michael

2006-01-01

A growing family of cellular proteins encoding the caspase activation and recruitment domain (CARD) has a crucial role in immunity by sensing virus infection and signaling antiviral immune defenses. Four independent studies have identified a novel CARD-containing protein, variously called IPS-1, MAVS, VISA and Cardif, which is an essential signaling adaptor of the host defense mediating CARD-CARD interactions with retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDAS), sensors of virus infection. Disruption of this novel signaling pathway by hepatitis C virus (HCV) might provide a foundation for viral persistence.

Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

PubMed Central

Domm, William; Misra, Ravi S.; O’Reilly, Michael A.

2015-01-01

Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health. PMID:26322310

South African Defense Policy.

DTIC Science & Technology

1984-06-01

apartheid policy and ensure Afrikaner control of the government through legislation and regulation. While a survey of the actual implementation of apartheid...from the government’s subse- quent actions that much of the defense legislation introduced 35 during early 1961 was aimed at strengthening internal...National Party. As the expression of Western European political liberalism, the Westminister system made it difficult to maintain government secrecy, and

ESRRA (estrogen-related receptor α) is a key coordinator of transcriptional and post-translational activation of autophagy to promote innate host defense.

PubMed

Kim, Soo Yeon; Yang, Chul-Su; Lee, Hye-Mi; Kim, Jin Kyung; Kim, Yi-Sak; Kim, Ye-Ram; Kim, Jae-Sung; Kim, Tae Sung; Yuk, Jae-Min; Dufour, Catherine Rosa; Lee, Sang-Hee; Kim, Jin-Man; Choi, Hueng-Sik; Giguère, Vincent; Jo, Eun-Kyeong

2018-01-01

The orphan nuclear receptor ESRRA (estrogen-related receptor α) is a key regulator of energy homeostasis and mitochondrial function. Macroautophagy/autophagy, an intracellular degradation process, is a critical innate effector against intracellular microbes. Here, we demonstrate that ESRRA is required for the activation of autophagy to promote innate antimicrobial defense against mycobacterial infection. AMP-activated protein kinase pathway and SIRT1 (sirtuin 1) activation led to induction of ESRRA, which is essential for autophagosome formation, in bone marrow-derived macrophages. ESRRA enhanced the transcriptional activation of numerous autophagy-related (Atg) genes containing ERR response elements in their promoter regions. Furthermore, ESRRA, operating in a feed-forward loop with SIRT1, was required for autophagy activation through deacetylation of ATG5, BECN1, and ATG7. Importantly, ESRRA deficiency resulted in a decrease of phagosomal maturation and antimicrobial responses against mycobacterial infection. Thus, we identify ESRRA as a critical activator of autophagy via both transcriptional and post-translational control to promote antimicrobial host responses.

Host Immune Response to Influenza A Virus Infection.

PubMed

Chen, Xiaoyong; Liu, Shasha; Goraya, Mohsan Ullah; Maarouf, Mohamed; Huang, Shile; Chen, Ji-Long

2018-01-01

Influenza A viruses (IAVs) are contagious pathogens responsible for severe respiratory infection in humans and animals worldwide. Upon detection of IAV infection, host immune system aims to defend against and clear the viral infection. Innate immune system is comprised of physical barriers (mucus and collectins), various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, which provide first line of defense against IAV infection. The adaptive immunity is mediated by B cells and T cells, characterized with antigen-specific memory cells, capturing and neutralizing the pathogen. The humoral immune response functions through hemagglutinin-specific circulating antibodies to neutralize IAV. In addition, antibodies can bind to the surface of infected cells and induce antibody-dependent cell-mediated cytotoxicity or complement activation. Although there are neutralizing antibodies against the virus, cellular immunity also plays a crucial role in the fight against IAVs. On the other hand, IAVs have developed multiple strategies to escape from host immune surveillance for successful replication. In this review, we discuss how immune system, especially innate immune system and critical molecules are involved in the antiviral defense against IAVs. In addition, we highlight how IAVs antagonize different immune responses to achieve a successful infection.

Venom of Parasitoid Pteromalus puparum Impairs Host Humoral Antimicrobial Activity by Decreasing Host Cecropin and Lysozyme Gene Expression

PubMed Central

Fang, Qi; Wang, Bei-Bei; Ye, Xin-Hai; Wang, Fei; Ye, Gong-Yin

2016-01-01

Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Here, we report that Pteromalus puparum venom impairs the antimicrobial activity of its host Pieris rapae. Inhibition zone results showed that bead injection induced the antimicrobial activity of the host hemolymph but that venom inhibited it. The cDNAs encoding cecropin and lysozyme were screened. Relative quantitative PCR results indicated that all of the microorganisms and bead injections up-regulated the transcript levels of the two genes but that venom down-regulated them. At 8 h post bead challenge, there was a peak in the transcript level of the cecropin gene, whereas the peak of lysozyme gene occurred at 24 h. The transcripts levels of the two genes were higher in the granulocytes and fat body than in other tissues. RNA interference decreased the transcript levels of the two genes and the antimicrobial activity of the pupal hemolymph. Venom injections similarly silenced the expression of the two genes during the first 8 h post-treatment in time- and dose-dependent manners, after which the silence effects abated. Additionally, recombinant cecropin and lysozyme had no significant effect on the emergence rate of pupae that were parasitized by P. puparum females. These findings suggest one mechanism of impairing host antimicrobial activity by parasitoid venom. PMID:26907346

Cross-talk of the biotrophic pathogen Claviceps purpurea and its host Secale cereale.

PubMed

Oeser, Birgitt; Kind, Sabine; Schurack, Selma; Schmutzer, Thomas; Tudzynski, Paul; Hinsch, Janine

2017-04-04

The economically important Ergot fungus Claviceps purpurea is an interesting biotrophic model system because of its strict organ specificity (grass ovaries) and the lack of any detectable plant defense reactions. Though several virulence factors were identified, the exact infection mechanisms are unknown, e.g. how the fungus masks its attack and if the host detects the infection at all. We present a first dual transcriptome analysis using an RNA-Seq approach. We studied both, fungal and plant gene expression in young ovaries infected by the wild-type and two virulence-attenuated mutants. We can show that the plant recognizes the fungus, since defense related genes are upregulated, especially several phytohormone genes. We present a survey of in planta expressed fungal genes, among them several confirmed virulence genes. Interestingly, the set of most highly expressed genes includes a high proportion of genes encoding putative effectors, small secreted proteins which might be involved in masking the fungal attack or interfering with host defense reactions. As known from several other phytopathogens, the C. purpurea genome contains more than 400 of such genes, many of them clustered and probably highly redundant. Since the lack of effective defense reactions in spite of recognition of the fungus could very well be achieved by effectors, we started a functional analysis of some of the most highly expressed candidates. However, the redundancy of the system made the identification of a drastic effect of a single gene most unlikely. We can show that at least one candidate accumulates in the plant apoplast. Deletion of some candidates led to a reduced virulence of C. purpurea on rye, indicating a role of the respective proteins during the infection process. We show for the first time that- despite the absence of effective plant defense reactions- the biotrophic pathogen C. purpurea is detected by its host. This points to a role of effectors in modulation of the effective

Using host-pathogen protein interactions to identify and characterize Francisella tularensis virulence factors.

PubMed

Wallqvist, Anders; Memišević, Vesna; Zavaljevski, Nela; Pieper, Rembert; Rajagopala, Seesandra V; Kwon, Keehwan; Yu, Chenggang; Hoover, Timothy A; Reifman, Jaques

2015-12-29

Francisella tularensis is a select bio-threat agent and one of the most virulent intracellular pathogens known, requiring just a few organisms to establish an infection. Although several virulence factors are known, we lack an understanding of virulence factors that act through host-pathogen protein interactions to promote infection. To address these issues in the highly infectious F. tularensis subsp. tularensis Schu S4 strain, we deployed a combined in silico, in vitro, and in vivo analysis to identify virulence factors and their interactions with host proteins to characterize bacterial infection mechanisms. We initially used comparative genomics and literature to identify and select a set of 49 putative and known virulence factors for analysis. Each protein was then subjected to proteome-scale yeast two-hybrid (Y2H) screens with human and murine cDNA libraries to identify potential host-pathogen protein-protein interactions. Based on the bacterial protein interaction profile with both hosts, we selected seven novel putative virulence factors for mutant construction and animal validation experiments. We were able to create five transposon insertion mutants and used them in an intranasal BALB/c mouse challenge model to establish 50 % lethal dose estimates. Three of these, ΔFTT0482c, ΔFTT1538c, and ΔFTT1597, showed attenuation in lethality and can thus be considered novel F. tularensis virulence factors. The analysis of the accompanying Y2H data identified intracellular protein trafficking between the early endosome to the late endosome as an important component in virulence attenuation for these virulence factors. Furthermore, we also used the Y2H data to investigate host protein binding of two known virulence factors, showing that direct protein binding was a component in the modulation of the inflammatory response via activation of mitogen-activated protein kinases and in the oxidative stress response. Direct interactions with specific host proteins and the

Stress responses in Streptococcus species and their effects on the host.

PubMed

Nguyen, Cuong Thach; Park, Sang-Sang; Rhee, Dong-Kwon

2015-11-01

Streptococci cause a variety of diseases, such as dental caries, pharyngitis, meningitis, pneumonia, bacteremia, endocarditis, erysipelas, and necrotizing fasciitis. The natural niche of this genus of bacteria ranges from the mouth and nasopharynx to the skin, indicating that the bacteria will inevitably be subjected to environmental changes during invasion into the host, where it is exposed to the host immune system. Thus, the Streptococcus-host interaction determines whether bacteria are cleared by the host's defenses or whether they survive after invasion to cause serious diseases. If this interaction was to be deciphered, it could aid in the development of novel preventive and therapeutic agents. Streptococcus species possess many virulent factors, such as peroxidases and heat-shock proteins (HSPs), which play key roles in protecting the bacteria from hostile host environments. This review will discuss insights into the mechanism(s) by which streptococci adapt to host environments. Additionally, we will address how streptococcal infections trigger host stress responses; however, the mechanism by which bacterial components modulate host stress responses remains largely unknown.

Bacterial Surface Glycans: Microarray and QCM Strategies for Glycophenotyping and Exploration of Recognition by Host Receptors.

PubMed

Kalograiaki, Ioanna; Campanero-Rhodes, María A; Proverbio, Davide; Euba, Begoña; Garmendia, Junkal; Aastrup, Teodor; Solís, Dolores

2018-01-01

Bacterial surfaces are decorated with a diversity of carbohydrate structures that play important roles in the bacteria-host relationships. They may offer protection against host defense mechanisms, elicit strong antigenic responses, or serve as ligands for host receptors, including lectins of the innate immune system. Binding by these lectins may trigger defense responses or, alternatively, promote attachment, thereby enhancing infection. The outcome will depend on the particular bacterial surface landscape, which may substantially differ among species and strains. In this chapter, we describe two novel methods for exploring interactions directly on the bacterial surface, based on the generation of bacterial microarrays and quartz crystal microbalance (QCM) sensor chips. Bacterial microarrays enable profiling of accessible carbohydrate structures and screening of their recognition by host receptors, also providing information on binding avidity, while the QCM approach allows determination of binding affinity and kinetics. In both cases, the chief element is the use of entire bacterial cells, so that recognition of the bacterial glycan epitopes is explored in their natural environment. © 2018 Elsevier Inc. All rights reserved.

Histophagous ciliate Pseudocollinia brintoni and bacterial assemblage interaction with krill Nyctiphanes simplex. II. Host responses.

PubMed

Gómez-Gutiérrez, Jaime; Angel-Rodríguez, Jorge A; Tremblay, Nelly; Zenteno-Savín, Tania; Aguilar-Méndez, Mario J; López-Cortés, Alejandro; Robinson, Carlos J

2015-10-27

Unlike decapod crustaceans of commercial interest, the krill defense system and its response to parasites and pathogens is virtually unknown. Histophagous ciliates of the genus Pseudocollinia interact with at least 7 krill species in the northeastern Pacific. Although they can cause epizootic events, the physiology of the histophagous ciliate-host interaction and krill (host) defenses remain unknown. From 1 oceanographic survey along the southwestern coast of the Baja California Peninsula near Bahía Magdalena and 2 in the Gulf of California, we investigated parasitoid-host physiological responses (fatty acid and oxidative stress indicators) of the subtropical krill Nyctiphanes simplex infected with the ciliate P. brintoni. All life stages of P. brintoni were associated with opportunistic bacterial assemblages that have not been explicitly investigated in other Pseudocollinia species (P. beringensis, P. oregonensis, and P. similis). Parasitoid ciliates exclusively infected adult females, which showed increased lipid content during gonad development. As the infection progressed, omega-3 eicosapentaenoic and docosahexaenoic fatty acids, which may act as energy sources to produce high numbers of ciliate transmission stages, were quickly depleted. Antioxidant enzymes, components of the crustacean defense system, varied throughout infection, but without inhibiting Pseudocollinia infection, i.e. higher levels of lipid oxidative damage were detected in late stages of infection. The ineffective response of the krill antioxidant defense system against histophagous ciliates and the bacteria associated with the ciliates suggests that Pseudocollinia ciliates are functionally analogous to krill predators and may have a strong influence on the population dynamics of krill.

Neurophysiological evidence of an association between cognitive control and defensive reactivity processes in young children.

PubMed

Lo, Sharon L; Schroder, Hans S; Moran, Tim P; Durbin, C Emily; Moser, Jason S

2015-10-01

Interactions between cognitive control and affective processes, such as defensive reactivity, are intimately involved in healthy and unhealthy human development. However, cognitive control and defensive reactivity processes are often studied in isolation and rarely examined in early childhood. To address these gaps, we examined the relationships between multiple neurophysiological measures of cognitive control and defensive reactivity in young children. Specifically, we assessed two event-related potentials thought to index cognitive control processes--the error-related negativity (ERN) and error positivity (Pe)--measured across two tasks, and two markers of defensive reactivity processes--startle reflex and resting parietal asymmetry--in a sample of 3- to 7-year old children. Results revealed that measures of cognitive control and defensive reactivity were related such that evidence of poor cognitive control (smaller ERN) was associated with high defensive reactivity (larger startle and greater right relative to left parietal activity). The strength of associations between the ERN and measures of defensive reactivity did not vary by age, providing evidence that poor cognitive control relates to greater defensive reactivity across early childhood years. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Modulating airway defenses against microbes.

PubMed

Reynolds, Herbert Y

2002-05-01

Prevention and treatment of respiratory infections remain an important health care challenge as the US population ages, contains more susceptible or high-risk people, and encounters new pathogens or antibiotic resistant bacteria. Reasonably protective vaccines against very common microbes are available for childhood and adult immunization, but, generally, these are underutilized. A broader definition of higher risk individuals is evolving, which will include more for immunization. Different approaches to vaccine development through design of new component vaccines are necessary. This review has updated host defense mechanisms at three levels in the human respiratory tract: naso-oropharynx (upper airways), conducting airways, and alveolar space. Examples of representative pathogenic microbes have been inserted at the respective airway segment where they may colonize or create infection (influenza, measles virus, Porphyromonas gingivalis causing periodontitis, Bordetella pertussis, Chlamydia pneumoniae, Streptococcus pneumoniae, and Bacillus anthracis ). Hopefully, microbe-host interactions will suggest new approaches for preventing these kinds of infections.

Strategies of Vibrio parahaemolyticus to acquire nutritional iron during host colonization

PubMed Central

León-Sicairos, Nidia; Angulo-Zamudio, Uriel A.; de la Garza, Mireya; Velázquez-Román, Jorge; Flores-Villaseñor, Héctor M.; Canizalez-Román, Adrian

2015-01-01

Iron is an essential element for the growth and development of virtually all living organisms. As iron acquisition is critical for the pathogenesis, a host defense strategy during infection is to sequester iron to restrict the growth of invading pathogens. To counteract this strategy, bacteria such as Vibrio parahaemolyticus have adapted to such an environment by developing mechanisms to obtain iron from human hosts. This review focuses on the multiple strategies employed by V. parahaemolyticus to obtain nutritional iron from host sources. In these strategies are included the use of siderophores and xenosiderophores, proteases and iron-protein receptor. The host sources used by V. parahaemolyticus are the iron-containing proteins transferrin, hemoglobin, and hemin. The implications of iron acquisition systems in the virulence of V. parahaemolyticus are also discussed. PMID:26217331

Developing Cyberspace Data Understanding: Using CRISP-DM for Host-based IDS Feature Mining

DTIC Science & Technology

2010-03-01

Developing Cyberspace Data Understanding: Using CRISP - DM for Host-based IDS Feature Mining THESIS Joseph R. Erskine, Captain, USAF AFIT/GCS/ENG/10-01...Air Force, Department of Defense, or the United States Government. AFIT/GCS/ENG/10-01 Developing Cyberspace Data Understanding: Using CRISP - DM for...Developing Cyberspace Data Understanding: Using CRISP - DM for Host-based IDS Feature Mining Joseph R. Erskine, B.S.C.S. Captain, USAF Approved: /signed/ 12

The cGAS-STING Defense Pathway and Its Counteraction by Viruses.

PubMed

Ma, Zhe; Damania, Blossom

2016-02-10

Upon virus infection, host cells mount a concerted innate immune response involving type I interferon and pro-inflammatory cytokines to enable elimination of the pathogen. Recently, cGAS and STING have been identified as intracellular sensors that activate the interferon pathway in response to virus infection and thus mediate host defense against a range of DNA and RNA viruses. Here we review how viruses are sensed by the cGAS-STING signaling pathway as well as how viruses modulate this pathway. Mechanisms utilized by viral proteins to inhibit cGAS and/or STING are also discussed. On the flip side, host cells have also evolved strategies to thwart viral immune escape. The balance between host immune control and viral immune evasion is pivotal to viral pathogenesis, and we discuss this virus-host stand-off in the context of the cGAS-STING innate immune pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense.

PubMed

Hansdottir, Sif; Monick, Martha M; Hinde, Sara L; Lovan, Nina; Look, Dwight C; Hunninghake, Gary W

2008-11-15

The role of vitamin D in innate immunity is increasingly recognized. Recent work has identified a number of tissues that express the enzyme 1alpha-hydroxylase and are able to activate vitamin D. This locally produced vitamin D is believed to have important immunomodulatory effects. In this paper, we show that primary lung epithelial cells express high baseline levels of activating 1alpha-hydroxylase and low levels of inactivating 24-hydroxylase. The result of this enzyme expression is that airway epithelial cells constitutively convert inactive 25-dihydroxyvitamin D(3) to the active 1,25-dihydroxyvitamin D(3). Active vitamin D that is generated by lung epithelium leads to increased expression of vitamin D-regulated genes with important innate immune functions. These include the cathelicidin antimicrobial peptide gene and the TLR coreceptor CD14. dsRNA increases the expression of 1alpha-hydroxylase, augments the production of active vitamin D, and synergizes with vitamin D to increase expression of cathelicidin. In contrast to induction of the antimicrobial peptide, vitamin D attenuates dsRNA-induced expression of the NF-kappaB-driven gene IL-8. We conclude that primary epithelial cells generate active vitamin D, which then influences the expression of vitamin D-driven genes that play a major role in host defense. Furthermore, the presence of vitamin D alters induction of antimicrobial peptides and inflammatory cytokines in response to viruses. These observations suggest a novel mechanism by which local conversion of inactive to active vitamin D alters immune function in the lung.

Rapid Host Defense against Aspergillus fumigatus Involves Alveolar Macrophages with a Predominance of Alternatively Activated Phenotype

PubMed Central

Bhatia, Shikha; Fei, Mingjian; Yarlagadda, Manohar; Qi, Zengbiao; Akira, Shizuo; Saijo, Shinobu; Iwakura, Yoichiro; van Rooijen, Nico; Gibson, Gregory A.; St. Croix, Claudette M.; Ray, Anuradha; Ray, Prabir

2011-01-01

The ubiquitous fungus Aspergillus fumigatus is associated with chronic diseases such as invasive pulmonary aspergillosis in immunosuppressed patients and allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis or severe asthma. Because of constant exposure to this fungus, it is critical for the host to exercise an immediate and decisive immune response to clear fungal spores to ward off disease. In this study, we observed that rapidly after infection by A. fumigatus, alveolar macrophages predominantly express Arginase 1 (Arg1), a key marker of alternatively activated macrophages (AAMs). The macrophages were also found to express Ym1 and CD206 that are also expressed by AAMs but not NOS2, which is expressed by classically activated macrophages. The expression of Arg1 was reduced in the absence of the known signaling axis, IL-4Rα/STAT6, for AAM development. While both Dectin-1 and TLR expressed on the cell surface have been shown to sense A. fumigatus, fungus-induced Arg1 expression in CD11c+ alveolar macrophages was not dependent on either Dectin-1 or the adaptor MyD88 that mediates intracellular signaling by most TLRs. Alveolar macrophages from WT mice efficiently phagocytosed fungal conidia, but those from mice deficient in Dectin-1 showed impaired fungal uptake. Depletion of macrophages with clodronate-filled liposomes increased fungal burden in infected mice. Collectively, our studies suggest that alveolar macrophages, which predominantly acquire an AAM phenotype following A. fumigatus infection, have a protective role in defense against this fungus. PMID:21246055

A Meloidogyne incognita effector MiISE5 suppresses programmed cell death to promote parasitism in host plant.

PubMed

Shi, Qianqian; Mao, Zhenchuan; Zhang, Xi; Zhang, Xiaoping; Wang, Yunsheng; Ling, Jian; Lin, Runmao; Li, Denghui; Kang, Xincong; Sun, Wenxian; Xie, Bingyan

2018-05-08

Root-knot nematodes (RKNs) are highly specialized parasites that interact with their host plants using a range of strategies. The esophageal glands are the main places where nematodes synthesize effector proteins, which play central roles in successful invasion. The Meloidogyne incognita effector MiISE5 is exclusively expressed within the subventral esophageal cells and is upregulated during early parasitic stages. In this study, we show that MiISE5 can be secreted to barley cells through infectious hyphae of Magnaporthe oryzae. Transgenic Arabidopsis plants expressing MiISE5 became significantly more susceptible to M. incognita. Inversely, the tobacco rattle virus (TRV)-mediated silence of MiISE5 decreased nematode parasitism. Moreover, transient expression of MiISE5 suppressed cell death caused by Burkholderia glumae in Nicotiana benthamiana. Based on transcriptome analysis of MiISE5 transgenic sample and the wild-type (WT) sample, we obtained 261 DEGs, and the results of GO and KEGG enrichment analysis indicate that MiISE5 can interfere with various metabolic and signaling pathways, especially the JA signaling pathway, to facilitate nematode parasitism. Results from the present study suggest that MiISE5 plays an important role during the early stages of parasitism and provides evidence to decipher the molecular mechanisms underlying the manipulation of host immune defense responses by M. incognita.

Flower-specific jasmonate signaling regulates constitutive floral defenses in wild tobacco

PubMed Central

Li, Ran; Wang, Ming; Wang, Yang; Schuman, Meredith C.; Weinhold, Arne; Schäfer, Martin; Jiménez-Alemán, Guillermo H.; Barthel, Andrea; Baldwin, Ian T.

2017-01-01

Optimal defense (OD) theory predicts that within a plant, tissues are defended in proportion to their fitness value and risk of predation. The fitness value of leaves varies greatly and leaves are protected by jasmonate (JA)-inducible defenses. Flowers are vehicles of Darwinian fitness in flowering plants and are attacked by herbivores and pathogens, but how they are defended is rarely investigated. We used Nicotiana attenuata, an ecological model plant with well-characterized herbivore interactions to characterize defense responses in flowers. Early floral stages constitutively accumulate greater amounts of two well-characterized defensive compounds, the volatile (E)-α-bergamotene and trypsin proteinase inhibitors (TPIs), which are also found in herbivore-induced leaves. Plants rendered deficient in JA biosynthesis or perception by RNA interference had significantly attenuated floral accumulations of defensive compounds known to be regulated by JA in leaves. By RNA-seq, we found a JAZ gene, NaJAZi, specifically expressed in early-stage floral tissues. Gene silencing revealed that NaJAZi functions as a flower-specific jasmonate repressor that regulates JAs, (E)-α-bergamotene, TPIs, and a defensin. Flowers silenced in NaJAZi are more resistant to tobacco budworm attack, a florivore. When the defensin was ectopically expressed in leaves, performance of Manduca sexta larvae, a folivore, decreased. NaJAZi physically interacts with a newly identified NINJA-like protein, but not the canonical NINJA. This NINJA-like recruits the corepressor TOPLESS that contributes to the suppressive function of NaJAZi on floral defenses. This study uncovers the defensive function of JA signaling in flowers, which includes components that tailor JA signaling to provide flower-specific defense. PMID:28784761

A conserved mitochondrial surveillance pathway is required for defense against Pseudomonas aeruginosa.

PubMed

Tjahjono, Elissa; Kirienko, Natalia V

2017-06-01

All living organisms exist in a precarious state of homeostasis that requires constant maintenance. A wide variety of stresses, including hypoxia, heat, and infection by pathogens perpetually threaten to imbalance this state. Organisms use a battery of defenses to mitigate damage and restore normal function. Previously, we described a Caenorhabditis elegans-Pseudomonas aeruginosa assay (Liquid Killing) in which toxicity to the host is dependent upon the secreted bacterial siderophore pyoverdine. Although pyoverdine is also indispensable for virulence in mammals, its cytological effects are unclear. We used genetics, transcriptomics, and a variety of pathogen and chemical exposure assays to study the interactions between P. aeruginosa and C. elegans. Although P. aeruginosa can kill C. elegans through at least 5 different mechanisms, the defense responses activated by Liquid Killing are specific and selective and have little in common with innate defense mechanisms against intestinal colonization. Intriguingly, the defense response utilizes the phylogenetically-conserved ESRE (Ethanol and Stress Response Element) network, which we and others have previously shown to mitigate damage from a variety of abiotic stresses. This is the first report of this networks involvement in innate immunity, and indicates that host innate immune responses overlap with responses to abiotic stresses. The upregulation of the ESRE network in C. elegans is mediated in part by a family of bZIP proteins (including ZIP-2, ZIP-4, CEBP-1, and CEBP-2) that have overlapping and unique functions. Our data convincingly show that, following exposure to P. aeruginosa, the ESRE defense network is activated by mitochondrial damage, and that mitochondrial damage also leads to ESRE activation in mammals. This establishes a role for ESRE in a phylogenetically-conserved mitochondrial surveillance system important for stress response and innate immunity.

Virus versus Host Plant MicroRNAs: Who Determines the Outcome of the Interaction?

PubMed Central

Maghuly, Fatemeh; Ramkat, Rose C.; Laimer, Margit

2014-01-01

Considering the importance of microRNAs (miRNAs) in the regulation of essential processes in plant pathogen interactions, it is not surprising that, while plant miRNA sequences counteract viral attack via antiviral RNA silencing, viruses in turn have developed antihost defense mechanisms blocking these RNA silencing pathways and establish a counter-defense. In the current study, computational and stem-loop Reverse Transcription – Polymerase Chain Reaction (RT-PCR) approaches were employed to a) predict and validate virus encoded mature miRNAs (miRs) in 39 DNA-A sequences of the bipartite genomes of African cassava mosaic virus (ACMV) and East African cassava mosaic virus-Uganda (EACMV-UG) isolates, b) determine whether virus encoded miRs/miRs* generated from the 5′/3′ harpin arms have the capacity to bind to genomic sequences of the host plants Jatropha or cassava and c) investigate whether plant encoded miR/miR* sequences have the potential to bind to the viral genomes. Different viral pre-miRNA hairpin sequences and viral miR/miR* length variants occurring as isomiRs were predicted in both viruses. These miRNAs were located in three Open Reading Frames (ORFs) and in the Intergenic Region (IR). Moreover, various target genes for miRNAs from both viruses were predicted and annotated in the host plant genomes indicating that they are involved in biotic response, metabolic pathways and transcription factors. Plant miRs/miRs* from conserved and highly expressed families were identified, which were shown to have potential targets in the genome of both begomoviruses, representing potential plant miRNAs mediating antiviral defense. This is the first assessment of predicted viral miRs/miRs* of ACMV and EACMV-UG and host plant miRNAs, providing a reference point for miRNA identification in pathogens and their hosts. These findings will improve the understanding of host- pathogen interaction pathways and the function of viral miRNAs in Euphorbiaceous crop plants. PMID

Type III secretion system effector proteins: double agents in bacterial disease and plant defense.

PubMed

Alfano, James R; Collmer, Alan

2004-01-01

Many phytopathogenic bacteria inject virulence effector proteins into plant cells via a Hrp type III secretion system (TTSS). Without the TTSS, these pathogens cannot defeat basal defenses, grow in plants, produce disease lesions in hosts, or elicit the hypersensitive response (HR) in nonhosts. Pathogen genome projects employing bioinformatic methods to identify TTSS Hrp regulon promoters and TTSS pathway targeting signals suggest that phytopathogenic Pseudomonas, Xanthomonas, and Ralstonia spp. harbor large arsenals of effectors. The Hrp TTSS employs customized cytoplasmic chaperones, conserved export components in the bacterial envelope (also used by the TTSS of animal pathogens), and a more specialized set of TTSS-secreted proteins to deliver effectors across the plant cell wall and plasma membrane. Many effectors can act as molecular double agents that betray the pathogen to plant defenses in some interactions and suppress host defenses in others. Investigations of the functions of effectors within plant cells have demonstrated the plasma membrane and nucleus as subcellular sites for several effectors, revealed some effectors to possess cysteine protease or protein tyrosine phosphatase activity, and provided new clues to the coevolution of bacterium-plant interactions.

Identification of the Crucial Residues in the Early Insertion of Pardaxin into Different Phospholipid Bilayers.

PubMed

Jafari, Majid; Mehrnejad, Faramarz; Aghdami, Raheleh; Chaparzadeh, Nader; Razaghi Moghadam Kashani, Zahra; Doustdar, Farahnoosh

2017-04-24

Antimicrobial peptides (AMPs) are part of the innate host defense system, and they are produced by living organisms to defend themselves against infections. Pardaxin is a cationic AMP with antimicrobial and antitumor activities that has potential to be used as a novel antibiotic or for drug delivery in cancer therapy. This peptide acts on the membrane of target cells and can lead to lysis using different mechanisms of action. Here, we conducted 4.5 μs all-atom molecular dynamics (MD) simulations to determine the critical fragments and residues of Pardaxin for early insertion into different lipid bilayers. Our results revealed that the N-terminal domain of the peptide, particularly the Phe 2 and (/or) Phe 3 residues, has a crucial role in early insertion, independent of the type of lipid bilayers.

Sequestration of host metabolism by an intracellular pathogen

PubMed Central

Gehre, Lena; Gorgette, Olivier; Perrinet, Stéphanie; Prevost, Marie-Christine; Ducatez, Mathieu; Giebel, Amanda M; Nelson, David E; Ball, Steven G; Subtil, Agathe

2016-01-01

For intracellular pathogens, residence in a vacuole provides a shelter against cytosolic host defense to the cost of limited access to nutrients. The human pathogen Chlamydia trachomatis grows in a glycogen-rich vacuole. How this large polymer accumulates there is unknown. We reveal that host glycogen stores shift to the vacuole through two pathways: bulk uptake from the cytoplasmic pool, and de novo synthesis. We provide evidence that bacterial glycogen metabolism enzymes are secreted into the vacuole lumen through type 3 secretion. Our data bring strong support to the following scenario: bacteria co-opt the host transporter SLC35D2 to import UDP-glucose into the vacuole, where it serves as substrate for de novo glycogen synthesis, through a remarkable adaptation of the bacterial glycogen synthase. Based on these findings we propose that parasitophorous vacuoles not only offer protection but also provide a microorganism-controlled metabolically active compartment essential for redirecting host resources to the pathogens. DOI: http://dx.doi.org/10.7554/eLife.12552.001 PMID:26981769

A physical/psychological and biological stress combine to enhance endoplasmic reticulum stress

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

Mondal, Tapan Kumar; Emeny, Rebecca T.; Gao, Donghong

The generation of an immune response against infectious and other foreign agents is substantially modified by allostatic load, which is increased with chemical, physical and/or psychological stressors. The physical/psychological stress from cold-restraint (CR) inhibits host defense against Listeria monocytogenes (LM), due to early effects of the catecholamine norepinephrine (NE) from sympathetic nerves on β1-adrenoceptors (β1AR) of immune cells. Although CR activates innate immunity within 2 h, host defenses against bacterial growth are suppressed 2–3 days after infection (Cao and Lawrence 2002). CR enhances inducible nitric oxide synthase (iNOS) expression and NO production. The early innate activation leads to cellular reduction-oxidationmore » (redox) changes of immune cells. Lymphocytes from CR-treated mice express fewer surface thiols. Splenic and hepatic immune cells also have fewer proteins with free thiols after CR and/or LM, and macrophages have less glutathione after the in vivo CR exposure or exposure to NE in vitro. The early induction of CR-induced oxidative stress elevates endoplasmic reticulum (ER) stress, which could interfere with keeping phagocytized LM within the phagosome or re-encapsuling LM by autophagy once they escape from the phagosome. ER stress-related proteins, such as glucose-regulated protein 78 (GRP78), have elevated expression with CR and LM. The results indicate that CR enhances the unfolded protein response (UPR), which interferes with host defenses against LM. Thus, it is postulated that increased stress, as exists with living conditions at low socioeconomic conditions, can lower host defenses against pathogens because of oxidative and ER stress processes. - Highlights: • Cold-restraint (physical/psychological stress) induces early oxidative stress. • The oxidative stress relates to catecholamine signaling beta-adrenoceptors. • Physical/psychological stress combines infection enhancing inflammation. • Endoplasmic

Mosaic genome structure of the barley powdery mildew pathogen and conservation of transcriptional programs in divergent hosts

PubMed Central

Hacquard, Stéphane; Kracher, Barbara; Maekawa, Takaki; Vernaldi, Saskia; Schulze-Lefert, Paul; Ver Loren van Themaat, Emiel

2013-01-01

Barley powdery mildew, Blumeria graminis f. sp. hordei (Bgh), is an obligate biotrophic ascomycete fungal pathogen that can grow and reproduce only on living cells of wild or domesticated barley (Hordeum sp.). Domestication and deployment of resistant barley cultivars by humans selected for amplification of Bgh isolates with different virulence combinations. We sequenced the genomes of two European Bgh isolates, A6 and K1, for comparative analysis with the reference genome of isolate DH14. This revealed a mosaic genome structure consisting of large isolate-specific DNA blocks with either high or low SNP densities. Some of the highly polymorphic blocks likely accumulated SNPs for over 10,000 years, well before the domestication of barley. These isolate-specific blocks of alternating monomorphic and polymorphic regions imply an exceptionally large standing genetic variation in the Bgh population and might be generated and maintained by rare outbreeding and frequent clonal reproduction. RNA-sequencing experiments with isolates A6 and K1 during four early stages of compatible and incompatible interactions on leaves of partially immunocompromised Arabidopsis mutants revealed a conserved Bgh transcriptional program during pathogenesis compared with the natural host barley despite ∼200 million years of reproductive isolation of these hosts. Transcripts encoding candidate-secreted effector proteins are massively induced in successive waves. A specific decrease in candidate-secreted effector protein transcript abundance in the incompatible interaction follows extensive transcriptional reprogramming of the host transcriptome and coincides with the onset of localized host cell death, suggesting a host-inducible defense mechanism that targets fungal effector secretion or production. PMID:23696672

A Host-Pathogen Interaction Screen Identifies ada2 as a Mediator of Candida glabrata Defenses Against Reactive Oxygen Species.

PubMed

Kounatidis, Ilias; Ames, Lauren; Mistry, Rupal; Ho, Hsueh-Lui; Haynes, Ken; Ligoxygakis, Petros

2018-05-04

Candida glabrata ( C. glabrata ) forms part of the normal human gut microbiota but can cause life-threatening invasive infections in immune-compromised individuals. C. glabrata displays high resistance to common azole antifungals, which necessitates new treatments. In this investigation, we identified five C. glabrata deletion mutants ( ∆ada2 , ∆bas1 , ∆ hir3, ∆ino2 and ∆met31 ) from a library of 196 transcription factor mutants that were unable to grow and activate an immune response in Drosophila larvae. This highlighted the importance of these transcription factors in C. glabrata infectivity. Further ex vivo investigation into these mutants revealed the requirement of C. glabrata ADA2 for oxidative stress tolerance. We confirmed this observation in vivo whereby growth of the C. glabrata Δada2 strain was permitted only in flies with suppressed production of reactive oxygen species (ROS). Conversely, overexpression of ADA2 promoted C. glabrata replication in infected wild type larvae resulting in larval killing. We propose that ADA2 orchestrates the response of C. glabrata against ROS-mediated immune defenses during infection. With the need to find alternative antifungal treatment for C. glabrata infections, genes required for survival in the host environment, such as ADA2 , provide promising potential targets. Copyright © 2018 Kounatidis et al.

Chemical and Mechanical Defenses Vary among Maternal Lines and Leaf Ages in Verbascum thapsus L. (Scrophulariaceae) and Reduce Palatability to a Generalist Insect

PubMed Central

Alba, Christina; Bowers, M. Deane; Blumenthal, Dana; Hufbauer, Ruth A.

2014-01-01

Intra-specific variation in host-plant quality affects herbivore foraging decisions and, in turn, herbivore foraging decisions mediate plant fitness. In particular, variation in defenses against herbivores, both among and within plants, shapes herbivore behavior. If variation in defenses is genetically based, it can respond to natural selection by herbivores. We quantified intra-specific variation in iridoid glycosides, trichome length, and leaf strength in common mullein (Verbascum thapsus L, Scrophulariaceae) among maternal lines within a population and among leaves within plants, and related this variation to feeding preferences of a generalist herbivore, Trichopulsia ni Hübner. We found significant variation in all three defenses among maternal lines, with T. ni preferring plants with lower investment in chemical, but not mechanical, defense. Within plants, old leaves had lower levels of all defenses than young leaves, and were strongly preferred by T. ni. Caterpillars also preferred leaves with trichomes removed to leaves with trichomes intact. Differences among maternal lines indicate that phenotypic variation in defenses likely has a genetic basis. Furthermore, these results reveal that the feeding behaviors of T. ni map onto variation in plant defense in a predictable way. This work highlights the importance of variation in host-plant quality in driving interactions between plants and their herbivores. PMID:25127229

Challenges and Strategies for Proteome Analysis of the Interaction of Human Pathogenic Fungi with Host Immune Cells.

PubMed

Krüger, Thomas; Luo, Ting; Schmidt, Hella; Shopova, Iordana; Kniemeyer, Olaf

2015-12-14

Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.

Overcompensation of herbivore reproduction through hyper-suppression of plant defenses in response to competition.

PubMed

Schimmel, Bernardus C J; Ataide, Livia M S; Chafi, Rachid; Villarroel, Carlos A; Alba, Juan M; Schuurink, Robert C; Kant, Merijn R

2017-06-01

Spider mites are destructive arthropod pests on many crops. The generalist herbivorous mite Tetranychus urticae induces defenses in tomato (Solanum lycopersicum) and this constrains its fitness. By contrast, the Solanaceae-specialist Tetranychus evansi maintains a high reproductive performance by suppressing tomato defenses. Tetranychus evansi outcompetes T. urticae when infesting the same plant, but it is unknown whether this is facilitated by the defenses of the plant. We assessed the extent to which a secondary infestation by a competitor affects local plant defense responses (phytohormones and defense genes), mite gene expression and mite performance. We observed that T. evansi switches to hyper-suppression of defenses after its tomato host is also invaded by its natural competitor T. urticae. Jasmonate (JA) and salicylate (SA) defenses were suppressed more strongly, albeit only locally at the feeding site of T. evansi, upon introduction of T. urticae to the infested leaflet. The hyper-suppression of defenses coincided with increased expression of T. evansi genes coding for salivary defense-suppressing effector proteins and was paralleled by an increased reproductive performance. Together, these observations suggest that T. evansi overcompensates its reproduction through hyper-suppression of plant defenses in response to nearby competitors. We hypothesize that the competitor-induced overcompensation promotes competitive population growth of T. evansi on tomato. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Metabolic host responses to infection by intracellular bacterial pathogens

PubMed Central

Eisenreich, Wolfgang; Heesemann, Jürgen; Rudel, Thomas; Goebel, Werner

2013-01-01

The interaction of bacterial pathogens with mammalian hosts leads to a variety of physiological responses of the interacting partners aimed at an adaptation to the new situation. These responses include multiple metabolic changes in the affected host cells which are most obvious when the pathogen replicates within host cells as in case of intracellular bacterial pathogens. While the pathogen tries to deprive nutrients from the host cell, the host cell in return takes various metabolic countermeasures against the nutrient theft. During this conflicting interaction, the pathogen triggers metabolic host cell responses by means of common cell envelope components and specific virulence-associated factors. These host reactions generally promote replication of the pathogen. There is growing evidence that pathogen-specific factors may interfere in different ways with the complex regulatory network that controls the carbon and nitrogen metabolism of mammalian cells. The host cell defense answers include general metabolic reactions, like the generation of oxygen- and/or nitrogen-reactive species, and more specific measures aimed to prevent access to essential nutrients for the respective pathogen. Accurate results on metabolic host cell responses are often hampered by the use of cancer cell lines that already exhibit various de-regulated reactions in the primary carbon metabolism. Hence, there is an urgent need for cellular models that more closely reflect the in vivo infection conditions. The exact knowledge of the metabolic host cell responses may provide new interesting concepts for antibacterial therapies. PMID:23847769

African swine fever virus controls the host transcription and cellular machinery of protein synthesis.

PubMed

Sánchez, Elena G; Quintas, Ana; Nogal, Marisa; Castelló, Alfredo; Revilla, Yolanda

2013-04-01

Throughout a viral infection, the infected cell reprograms the gene expression pattern in order to establish a satisfactory antiviral response. African swine fever virus (ASFV), like other complex DNA viruses, sets up a number of strategies to evade the host's defense systems, such as apoptosis, inflammation and immune responses. The capability of the virus to persist in its natural hosts and in domestic pigs, which recover from infection with less virulent isolates, suggests that the virus displays effective mechanisms to escape host defense systems. ASFV has been described to regulate the activation of several transcription factors, thus regulating the activation of specific target genes during ASFV infection. Whereas some reports have concerned about anti-apoptotic ASFV genes and the molecular mechanisms by which ASFV interferes with inducible gene transcription and immune evasion, less is yet known regarding how ASFV regulates the translational machinery in infected cells, although a recent report has shown a mechanism for favored expression of viral genes based on compartmentalization of viral mRNA and ribosomes with cellular translation factors within the virus factory. The viral mechanisms involved both in the regulation of host genes transcription and in the control of cellular protein synthesis are summarized in this review. Copyright © 2012 Elsevier B.V. All rights reserved.

Insect response to plant defensive protease inhibitors.

PubMed

Zhu-Salzman, Keyan; Zeng, Rensen

2015-01-07

Plant protease inhibitors (PIs) are natural plant defense proteins that inhibit proteases of invading insect herbivores. However, their anti-insect efficacy is determined not only by their potency toward a vulnerable insect system but also by the response of the insect to such a challenge. Through the long history of coevolution with their host plants, insects have developed sophisticated mechanisms to circumvent antinutritional effects of dietary challenges. Their response takes the form of changes in gene expression and the protein repertoire in cells lining the alimentary tract, the first line of defense. Research in insect digestive proteases has revealed the crucial roles they play in insect adaptation to plant PIs and has brought about a new appreciation of how phytophagous insects employ this group of molecules in both protein digestion and counterdefense. This review provides researchers in related fields an up-to-date summary of recent advances.

The host galaxy/AGN connection in nearby early-type galaxies. Is there a miniature radio-galaxy in every "core" galaxy?

NASA Astrophysics Data System (ADS)

Balmaverde, B.; Capetti, A.

2006-02-01

This is the second of a series of three papers exploring the connection between the multiwavelength properties of AGN in nearby early-type galaxies and the characteristics of their hosts. We selected two samples with 5 GHz VLA radio flux measurements down to 1 mJy, reaching levels of radio luminosity as low as 1036 erg s-1. In Paper I we presented a study of the surface brightness profiles for the 65 objects with available archival HST images out of the 116 radio-detected galaxies. We classified early-type galaxies into "core" and "power-law" galaxies, discriminating on the basis of the slope of their nuclear brightness profiles, following the Nukers scheme. Here we focus on the 29 core galaxies (hereafter CoreG). We used HST and Chandra data to isolate their optical and X-ray nuclear emission. The CoreG invariably host radio-loud nuclei, with an average radio-loudness parameter of Log R = L5 {GHz} / LB ˜ 3.6. The optical and X-ray nuclear luminosities correlate with the radio-core power, smoothly extending the analogous correlations already found for low luminosity radio-galaxies (LLRG) toward even lower power, by a factor of ˜ 1000, covering a combined range of 6 orders of magnitude. This supports the interpretation of a common non-thermal origin of the nuclear emission also for CoreG. The luminosities of the nuclear sources, most likely dominated by jet emission, set firm upper limits, as low as L/L_Edd ˜ 10-9 in both the optical and X-ray band, on any emission from the accretion process. The similarity of CoreG and LLRG when considering the distributions host galaxies luminosities and black hole masses, as well as of the surface brightness profiles, indicates that they are drawn from the same population of early-type galaxies. LLRG represent only the tip of the iceberg associated with (relatively) high activity levels, with CoreG forming the bulk of the population. We do not find any relationship between radio-power and black hole mass. A minimum black hole

Mancae of the parasitic cymothoid isopod, Anilocra apogonae: early life history, host-specificity, and effect on growth and survival of preferred young cardinal fishes

NASA Astrophysics Data System (ADS)

Fogelman, R. M.; Grutter, A. S.

2008-09-01

Juvenile parasitic cymothoid isopods (mancae) can injure or kill fishes, yet few studies have investigated their biology. While the definitive host of the adult cymothoids is usually a single host from a particular fish species, mancae may use so-called optional intermediate hosts before settling on the definitive host. Little, however, is known about these early interactions. The cymothoid isopod, Anilocra apogonae, infests the definitive host, Cheilodipterus quinquelineatus. This study examined their host preference among potential optional intermediate hosts. Their effect on the growth and mortality of the young of three apogonid fishes, including the definitive host, was investigated. The number of mancae produced per brood was positively correlated with female length. When given a choice of intermediate hosts, significantly more mancae attached to Apogon trimaculatus (Apogonidae) than to Apogon nigrofasciatus. When presented with Ap. trimaculatus and Pomacentrus amboinensis (Pomacentridae), mancae only attached to Ap. trimaculatus suggesting that mancae may show a taxonomic affiliation with preferred hosts. Mancae fed on all three apogonid species, with C. quinquelineatus being fed on earlier than Ap. trimaculatus and Ap. nigrofasciatus. Mancae feeding frequency, adjusted for fish survival, was lowest on C. quinquelineatus and highest on Ap. trimaculatus. Infested apogonids had reduced growth and increased mortality compared with uninfested fish. A. apogonae mancae can use several species of young apogonid fishes as optional intermediate hosts. Via reduced growth and increased mortality, mancae have the potential to negatively influence definitive host populations and also other young species of apogonid fishes.

The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response.

PubMed

Liu, Dong; Uzonna, Jude E

2012-01-01

The complicated interactions between Leishmania and the host antigen-presenting cells (APCs) have fundamental effects on the final outcome of the disease. Two major APCs, macrophages and dendritic cells (DCs), play critical roles in mediating resistance and susceptibility during Leishmania infection. Macrophages are the primary resident cell for Leishmania: they phagocytose and permit parasite proliferation. However, these cells are also the major effector cells to eliminate infection. The effective clearance of parasites by macrophages depends on activation of appropriate immune response, which is usually initiated by DCs. Here, we review the early interaction of APCs with Leishmania parasites and how these interactions profoundly impact on the ensuing adaptive immune response. We also discuss how the current knowledge will allow further refinement of our understanding of the interplay between Leishmania and its hosts that leads to resistance or susceptibility.

The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response

PubMed Central

Liu, Dong; Uzonna, Jude E.

2012-01-01

The complicated interactions between Leishmania and the host antigen-presenting cells (APCs) have fundamental effects on the final outcome of the disease. Two major APCs, macrophages and dendritic cells (DCs), play critical roles in mediating resistance and susceptibility during Leishmania infection. Macrophages are the primary resident cell for Leishmania: they phagocytose and permit parasite proliferation. However, these cells are also the major effector cells to eliminate infection. The effective clearance of parasites by macrophages depends on activation of appropriate immune response, which is usually initiated by DCs. Here, we review the early interaction of APCs with Leishmania parasites and how these interactions profoundly impact on the ensuing adaptive immune response. We also discuss how the current knowledge will allow further refinement of our understanding of the interplay between Leishmania and its hosts that leads to resistance or susceptibility. PMID:22919674

Immune defense and reproductive pace of life in Peromyscus mice.

PubMed

Martin, Lynn B; Weil, Zachary M; Nelson, Randy J

2007-10-01

Immune activity is variable within and among vertebrates despite the potentially large fitness costs of pathogens to their hosts. From the perspective of life history theory, immunological variability may be the consequence of counterbalancing investments in immune defense against other expensive physiological processes, namely, reproduction. In the present study, we tested the hypothesis that immune defense among captive-bred, disease-free Peromyscus mice would be influenced by their reproductive life history strategies. Specifically, we expected that small species that reproduce prolifically and mature rapidly (i.e., fast pace of life) would favor inexpensive, nonspecific immune defenses to promote reproductive proclivity. Alternatively, we expected that large species that mature slowly and invest modestly in reproduction over multiple events (i.e., slow pace of life) would favor developmentally expensive, specific immune defenses and avoid cheap, nonspecific ones because such defenses are predisposed to self-damage. We found that species exhibited either strong ability to kill (gram-negative) bacteria, a developmentally inexpensive defense, or strong ability to produce antibodies against a novel protein, a developmentally expensive defense, but not both. Cell-mediated inflammation also varied significantly among species, but in a unique fashion relative to bacteria killing or antibody production; wound healing was comparatively similar among species. These results indicate that Peromyscus species use immune strategies that are constrained to a dominant axis, but this axis is not determined solely by reproductive pace of life. Further comparisons, ideally with broader phylogenetic coverage, could identify what ecological and evolutionary forces produce the pattern we detected. Importantly, our study indicates that species may not be differentially immunocompetent; rather, they use unique defense strategies to prevent infection.