The sesquiterpene botrydial produced by Botrytis cinerea induces the hypersensitive response on plant tissues and its action is modulated by salicylic acid and jasmonic acid signaling.

PubMed

Rossi, Franco Rubén; Gárriz, Andrés; Marina, María; Romero, Fernando Matías; Gonzalez, María Elisa; Collado, Isidro González; Pieckenstain, Fernando Luis

2011-08-01

Botrytis cinerea, as a necrotrophic fungus, kills host tissues and feeds on the remains. This fungus is able to induce the hypersensitive response (HR) on its hosts, thus taking advantage on the host's defense machinery for generating necrotic tissues. However, the identity of HR effectors produced by B. cinerea is not clear. The aim of this work was to determine whether botrydial, a phytotoxic sesquiterpene produced by B. cinerea, is able to induce the HR on plant hosts, using Arabidopsis thaliana as a model. Botrydial induced the expression of the HR marker HSR3, callose deposition, and the accumulation of reactive oxygen species and phenolic compounds. Botrydial also induced the expression of PR1 and PDF1.2, two pathogenesis-related proteins involved in defense responses regulated by salicylic acid (SA) and jasmonic acid (JA), respectively. A. thaliana and tobacco plants defective in SA signaling were more resistant to botrydial than wild-type plants, as opposed to A. thaliana plants defective in JA signaling, which were more sensitive. It can be concluded that botrydial induces the HR on its hosts and its effects are modulated by host signaling pathways mediated by SA and JA.

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.

Emerging Role of D-Amino Acid Metabolism in the Innate Defense.

PubMed

Sasabe, Jumpei; Suzuki, Masataka

2018-01-01

Mammalian innate and adaptive immune systems use the pattern recognition receptors, such as toll-like receptors, to detect conserved bacterial and viral components. Bacteria synthesize diverse D-amino acids while eukaryotes and archaea generally produce two D-amino acids, raising the possibility that many of bacterial D-amino acids are bacteria-specific metabolites. Although D-amino acids have not been identified to bind to any known pattern recognition receptors, D-amino acids are enantioselectively recognized by some other receptors and enzymes including a flavoenzyme D-amino acid oxidase (DAO) in mammals. At host-microbe interfaces in the neutrophils and intestinal mucosa, DAO catalyzes oxidation of bacterial D-amino acids, such as D-alanine, and generates H 2 O 2 , which is linked to antimicrobial activity. Intestinal DAO also modifies the composition of microbiota through modulation of growth for some bacteria that are dependent on host nutrition. Furthermore, regulation and recognition of D-amino acids in mammals have additional meanings at various host-microbe interfaces; D-phenylalanine and D-tryptophan regulate chemotaxis of neutrophils through a G-coupled protein receptor, D-serine has a bacteriostatic role in the urinary tract, D-phenylalanine and D-leucine inhibit innate immunity through the sweet taste receptor in the upper airway, and D-tryptophan modulates immune tolerance in the lower airway. This mini-review highlights recent evidence supporting the hypothesis that D-amino acids are utilized as inter-kingdom communication at host-microbe interface to modulate bacterial colonization and host defense.

Phytophthora infestans RXLR Effector AVR1 Interacts with Exocyst Component Sec5 to Manipulate Plant Immunity.

PubMed

Du, Yu; Mpina, Mohamed H; Birch, Paul R J; Bouwmeester, Klaas; Govers, Francine

2015-11-01

Phytophthora infestans secretes numerous RXLR effectors that modulate host defense and thereby pave the way for successful invasion. Here, we show that the RXLR effector AVR1 is a virulence factor that promotes colonization and suppresses callose deposition, a hallmark of basal defense. To identify host targets of AVR1, we performed yeast two-hybrid screens and selected Sec5 as a candidate. Sec5 is a subunit of the exocyst, a protein complex that is involved in vesicle trafficking. AVR1-like (A-L), a close homolog of AVR1, also acts as a virulence factor, but unlike AVR1, A-L does not suppress CRINKLER2 (CRN2)-induced cell death or interact with Sec5. Compared with AVR1, A-L is shorter and lacks the carboxyl-terminal tail, the T-region that is crucial for CRN2-induced cell death suppression and Sec5 interaction. In planta analyses revealed that AVR1 and Sec5 are in close proximity, and coimmunoprecipitation confirmed the interaction. Sec5 is required for secretion of the pathogenesis-related protein PR-1 and callose deposition and also plays a role in CRN2-induced cell death. Our findings show that P. infestans manipulates an exocyst subunit and thereby potentially disturbs vesicle trafficking, a cellular process that is important for basal defense. This is a novel strategy that oomycete pathogens exploit to modulate host defense. © 2015 American Society of Plant Biologists. All Rights Reserved.

Phytophthora infestans RXLR Effector AVR1 Interacts with Exocyst Component Sec5 to Manipulate Plant Immunity1[OPEN

PubMed Central

Du, Yu; Mpina, Mohamed H.; Birch, Paul R.J.; Bouwmeester, Klaas; Govers, Francine

2015-01-01

Phytophthora infestans secretes numerous RXLR effectors that modulate host defense and thereby pave the way for successful invasion. Here, we show that the RXLR effector AVR1 is a virulence factor that promotes colonization and suppresses callose deposition, a hallmark of basal defense. To identify host targets of AVR1, we performed yeast two-hybrid screens and selected Sec5 as a candidate. Sec5 is a subunit of the exocyst, a protein complex that is involved in vesicle trafficking. AVR1-like (A-L), a close homolog of AVR1, also acts as a virulence factor, but unlike AVR1, A-L does not suppress CRINKLER2 (CRN2)-induced cell death or interact with Sec5. Compared with AVR1, A-L is shorter and lacks the carboxyl-terminal tail, the T-region that is crucial for CRN2-induced cell death suppression and Sec5 interaction. In planta analyses revealed that AVR1 and Sec5 are in close proximity, and coimmunoprecipitation confirmed the interaction. Sec5 is required for secretion of the pathogenesis-related protein PR-1 and callose deposition and also plays a role in CRN2-induced cell death. Our findings show that P. infestans manipulates an exocyst subunit and thereby potentially disturbs vesicle trafficking, a cellular process that is important for basal defense. This is a novel strategy that oomycete pathogens exploit to modulate host defense. PMID:26336092

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.

Antimicrobial Peptides: An Emerging Category of Therapeutic Agents.

PubMed

Mahlapuu, Margit; Håkansson, Joakim; Ringstad, Lovisa; Björn, Camilla

2016-01-01

Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

The Role of the Polymeric Immunoglobulin Receptor and Secretory Immunoglobulins during Mucosal Infection and Immunity.

PubMed

Turula, Holly; Wobus, Christiane E

2018-05-03

The gastrointestinal tract houses millions of microbes, and thus has evolved several host defense mechanisms to keep them at bay, and prevent their entry into the host. One such mucosal surface defense is the secretion of secretory immunoglobulins (SIg). Secretion of SIg depends on the polymeric immunoglobulin receptor (pIgR), which transports polymeric Ig (IgA or IgM) from the basolateral surface of the epithelium to the apical side. Upon reaching the luminal side, a portion of pIgR, called secretory component (SC) is cleaved off to release Ig, forming SIg. Through antigen-specific and non-specific binding, SIg can modulate microbial communities and pathogenic microbes via several mechanisms: agglutination and exclusion from the epithelial surface, neutralization, or via host immunity and complement activation. Given the crucial role of SIg as a microbial scavenger, some pathogens also evolved ways to modulate and utilize pIgR and SIg to facilitate infection. This review will cover the regulation of the pIgR/SIg cycle, mechanisms of SIg-mediated mucosal protection as well as pathogen utilization of SIg.

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

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.

Insights into Host Cell Modulation and Induction of New Cells by the Corn Smut Ustilago maydis.

PubMed

Redkar, Amey; Matei, Alexandra; Doehlemann, Gunther

2017-01-01

Many filamentous fungal pathogens induce drastic modulation of host cells causing abnormal infectious structures such as galls, or tumors that arise as a result of re-programming in the original developmental cell fate of a colonized host cell. Developmental consequences occur predominantly with biotrophic phytopathogens. This suggests that these host structures result as an outcome of efficient defense suppression and intimate fungal-host interaction to suit the pathogen's needs for completion of its infection cycle. This mini-review mainly summarizes host cell re-programming that occurs in the Ustilago maydis - maize interaction, in which the pathogen deploys cell-type specific effector proteins with varying activities. The fungus senses the physiological status and identity of colonized host cells and re-directs the endogenous developmental program of its host. The disturbance of host cell physiology and cell fate leads to novel cell shapes, increased cell size, and/or the number of host cells. We particularly highlight the strategies of U. maydis to induce physiologically varied host organs to form the characteristic tumors in both vegetative and floral parts of maize.

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.

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.

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.

The pleotropic role of statins: Could it be the imminent host modulation agent in periodontics?

PubMed

Grover, Harpreet Singh; Luthra, Shailly; Maroo, Shruti; Maroo, Niteeka

2013-03-01

Periodontal disease is a chronic inflammatory disease which represents a primarily anaerobic Gram-negative oral infection that results in gingival inflammation, loss of attachment, bone destruction. Bacterial endotoxins in the form of lipopolysaccharides (LPS) that are instrumental in generating a host-mediated tissue destructive immune response by mobilizing their defensive cells and releasing cytokines like Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6), which lead to tissue destruction by stimulating the production of the collagenolytic enzymes: Matrix metalloproteinases (MMPs). Since the host-mediated tissue destruction is to be controlled, various means have been employed for modulating this response. Statins, 3-hydroxy-3-methylglutarylcoenzyme A (HMG CoA) reductase inhibitors, besides having lipid-lowering abilities also have antioxidant, antithrombotic, anti-inflammatory, immunomodulatory and osteomodulatory properties. All of these pleiotropic effects of statins point out to it perhaps becoming the novel host modulation agent in periodontics.

The pleotropic role of statins: Could it be the imminent host modulation agent in periodontics?

PubMed Central

Grover, Harpreet Singh; Luthra, Shailly; Maroo, Shruti; Maroo, Niteeka

2013-01-01

Periodontal disease is a chronic inflammatory disease which represents a primarily anaerobic Gram-negative oral infection that results in gingival inflammation, loss of attachment, bone destruction. Bacterial endotoxins in the form of lipopolysaccharides (LPS) that are instrumental in generating a host-mediated tissue destructive immune response by mobilizing their defensive cells and releasing cytokines like Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and Interleukin-6 (IL-6), which lead to tissue destruction by stimulating the production of the collagenolytic enzymes: Matrix metalloproteinases (MMPs). Since the host-mediated tissue destruction is to be controlled, various means have been employed for modulating this response. Statins, 3-hydroxy-3-methylglutarylcoenzyme A (HMG CoA) reductase inhibitors, besides having lipid-lowering abilities also have antioxidant, antithrombotic, anti-inflammatory, immunomodulatory and osteomodulatory properties. All of these pleiotropic effects of statins point out to it perhaps becoming the novel host modulation agent in periodontics. PMID:23946727

Hypothesis: leukocyte endogenous mediator/endogenous pyrogen/lymphocyte-activating factor modulates the development of nonspecific and specific immunity and affects nutritional status.

PubMed

Powanda, M C; Beisel, W R

1982-04-01

We postulate that leukocyte endogenous mediator/endogenous pyrogen/lymphocyte-activating factor (LEM/EP/LAF) integrates the host's nonspecific and specific immune responses to infection by virtue of the panoply of physiological and metabolic activities it is capable of eliciting. The alterations in systemic metabolism modulated by LEM/EP/LAF, although apparently of value to the host in the defense against infection and the repair of tissue damage, result in negative nutrient balances. Severe infections, alone or in conjunction with injury, may result in malnutrition unless the patient is adequately nourished. Preexisting nutritional deficits can compromise host resistance to infection, in part by preventing production of LEM/EP/LAF. Additional studies of the sequelae of LEM/EP/LAF action and effects of nutrition on host resistance to infection appear warranted.

Agrobacterium tumefaciens Promotes Tumor Induction by Modulating Pathogen Defense in Arabidopsis thaliana[W

PubMed Central

Lee, Chil-Woo; Efetova, Marina; Engelmann, Julia C; Kramell, Robert; Wasternack, Claus; Ludwig-Müller, Jutta; Hedrich, Rainer; Deeken, Rosalia

2009-01-01

Agrobacterium tumefaciens causes crown gall disease by transferring and integrating bacterial DNA (T-DNA) into the plant genome. To examine the physiological changes and adaptations during Agrobacterium-induced tumor development, we compared the profiles of salicylic acid (SA), ethylene (ET), jasmonic acid (JA), and auxin (indole-3-acetic acid [IAA]) with changes in the Arabidopsis thaliana transcriptome. Our data indicate that host responses were much stronger toward the oncogenic strain C58 than to the disarmed strain GV3101 and that auxin acts as a key modulator of the Arabidopsis–Agrobacterium interaction. At initiation of infection, elevated levels of IAA and ET were associated with the induction of host genes involved in IAA, but not ET signaling. After T-DNA integration, SA as well as IAA and ET accumulated, but JA did not. This did not correlate with SA-controlled pathogenesis-related gene expression in the host, although high SA levels in mutant plants prevented tumor development, while low levels promoted it. Our data are consistent with a scenario in which ET and later on SA control virulence of agrobacteria, whereas ET and auxin stimulate neovascularization during tumor formation. We suggest that crosstalk among IAA, ET, and SA balances pathogen defense launched by the host and tumor growth initiated by agrobacteria. PMID:19794116

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 pathogen emergence. PMID:25375140

Dietary modulation of inflammation

USDA-ARS?s Scientific Manuscript database

Inflammation is heightened innate immune response caused by infection or wound. It is a part of essential immune responses for host defense against invading pathogens and wound healing which are the key biological processes necessary for the survival of all multi-cellular organisms. In mammals, it i...

Microbial modulation of bacoside A biosynthetic pathway and systemic defense mechanism in Bacopa monnieri under Meloidogyne incognita stress.

PubMed

Gupta, Rupali; Singh, Akanksha; Srivastava, Madhumita; Singh, Vivek; Gupta, M M; Pandey, Rakesh

2017-02-03

Plant-associated beneficial microbes have been explored to fulfill the imperative function for plant health. However, their impact on the host secondary metabolite production and nematode disease management remains elusive. Our present work has shown that chitinolytic microbes viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 singly as well as in combination modulated the biosynthetic pathway of bacoside A and systemic defense mechanism against Meloidogyne incognita in Bacopa monnieri. Interestingly, expression of bacoside biosynthetic pathway genes (3-Hydroxy-3-methylglutaryl coenzyme A reductase, mevalonate diphosphate decarboxylase, and squalene synthase) were upregulated in plants treated with the microbial combination in the presence as well as in absence of M. incognita stress. These microbes not only augmented bacoside A production (1.5 fold) but also strengthened host resistance via enhancement in chlorophyll a, defense enzymes and phenolic compounds like gallic acid, syringic acid, ferulic acid and cinnamic acid. Furthermore, elevated lignification and callose deposition in the microbial combination treated plants corroborate well with the above findings. Overall, the results provide novel insights into the underlying mechanisms of priming by beneficial microbes and underscore their capacity to trigger bacoside A production in B. monnieri under biotic stress.

Modulation of host immunity by beneficial microbes.

PubMed

Zamioudis, Christos; Pieterse, Corné M J

2012-02-01

In nature, plants abundantly form beneficial associations with soilborne microbes that are important for plant survival and, as such, affect plant biodiversity and ecosystem functioning. Classical examples of symbiotic microbes are mycorrhizal fungi that aid in the uptake of water and minerals, and Rhizobium bacteria that fix atmospheric nitrogen for the plant. Several other types of beneficial soilborne microbes, such as plant-growth-promoting rhizobacteria and fungi with biological control activity, can stimulate plant growth by directly suppressing deleterious soilborne pathogens or by priming aboveground plant parts for enhanced defense against foliar pathogens or insect herbivores. The establishment of beneficial associations requires mutual recognition and substantial coordination of plant and microbial responses. A growing body of evidence suggests that beneficial microbes are initially recognized as potential invaders, after which an immune response is triggered, whereas, at later stages of the interaction, mutualists are able to short-circuit plant defense responses to enable successful colonization of host roots. Here, we review our current understanding of how symbiotic and nonsymbiotic beneficial soil microbes modulate the plant immune system and discuss the role of local and systemic defense responses in establishing the delicate balance between the two partners.

Modulating the Levels of Plant Hormone Cytokinins at the Host-Pathogen Interface.

PubMed

Naseem, Muhammad; Shams, Shabana; Roitsch, Thomas

2017-01-01

Cytokinins are adenine and non-adenine derived heterogeneous class of regulatory molecules that participate in almost every aspect of plant biology. They also affect plant defense responses as well as help microbial pathogens to establish pathogenesis. The functional approaches that ensure desired and subtle modulations in the levels of plant cytokinins are highly instrumental in assessing their functions in plant immunity. Here, we describe a detailed working protocol regarding the enhanced production of cytokinins from plants that harbor isopentenyltransferase (IPT) enzyme gene under the control of 4xJERE (jasmonic acid and elicitor-responsive element) pathogen-inducible promoter. Our devised expression system is a context-dependent solution when it comes to investigating host-pathogen interactions under the modulated conditions of plant cytokinins.

Peptidoglycan recognition proteins in Drosophila immunity.

PubMed

Kurata, Shoichiro

2014-01-01

Innate immunity is the front line of self-defense against infectious non-self in vertebrates and invertebrates. The innate immune system is mediated by germ-line encoding pattern recognition molecules (pathogen sensors) that recognize conserved molecular patterns present in the pathogens but absent in the host. Peptidoglycans (PGN) are essential cell wall components of almost all bacteria, except mycoplasma lacking a cell wall, which provides the host immune system an advantage for detecting invading bacteria. Several families of pattern recognition molecules that detect PGN and PGN-derived compounds have been indentified, and the role of PGRP family members in host defense is relatively well-characterized in Drosophila. This review focuses on the role of PGRP family members in the recognition of invading bacteria and the activation and modulation of immune responses in Drosophila. Copyright © 2013 Elsevier Ltd. All rights reserved.

Apoplastic Venom Allergen-like Proteins of Cyst Nematodes Modulate the Activation of Basal Plant Innate Immunity by Cell Surface Receptors

PubMed Central

Lozano-Torres, Jose L.; Wilbers, Ruud H. P.; Warmerdam, Sonja; Finkers-Tomczak, Anna; Diaz-Granados, Amalia; van Schaik, Casper C.; Helder, Johannes; Bakker, Jaap; Goverse, Aska; Schots, Arjen; Smant, Geert

2014-01-01

Despite causing considerable damage to host tissue during the onset of parasitism, nematodes establish remarkably persistent infections in both animals and plants. It is thought that an elaborate repertoire of effector proteins in nematode secretions suppresses damage-triggered immune responses of the host. However, the nature and mode of action of most immunomodulatory compounds in nematode secretions are not well understood. Here, we show that venom allergen-like proteins of plant-parasitic nematodes selectively suppress host immunity mediated by surface-localized immune receptors. Venom allergen-like proteins are uniquely conserved in secretions of all animal- and plant-parasitic nematodes studied to date, but their role during the onset of parasitism has thus far remained elusive. Knocking-down the expression of the venom allergen-like protein Gr-VAP1 severely hampered the infectivity of the potato cyst nematode Globodera rostochiensis. By contrast, heterologous expression of Gr-VAP1 and two other venom allergen-like proteins from the beet cyst nematode Heterodera schachtii in plants resulted in the loss of basal immunity to multiple unrelated pathogens. The modulation of basal immunity by ectopic venom allergen-like proteins in Arabidopsis thaliana involved extracellular protease-based host defenses and non-photochemical quenching in chloroplasts. Non-photochemical quenching regulates the initiation of the defense-related programmed cell death, the onset of which was commonly suppressed by venom allergen-like proteins from G. rostochiensis, H. schachtii, and the root-knot nematode Meloidogyne incognita. Surprisingly, these venom allergen-like proteins only affected the programmed cell death mediated by surface-localized immune receptors. Furthermore, the delivery of venom allergen-like proteins into host tissue coincides with the enzymatic breakdown of plant cell walls by migratory nematodes. We, therefore, conclude that parasitic nematodes most likely utilize venom allergen-like proteins to suppress the activation of defenses by immunogenic breakdown products in damaged host tissue. PMID:25500833

Apoplastic venom allergen-like proteins of cyst nematodes modulate the activation of basal plant innate immunity by cell surface receptors.

PubMed

Lozano-Torres, Jose L; Wilbers, Ruud H P; Warmerdam, Sonja; Finkers-Tomczak, Anna; Diaz-Granados, Amalia; van Schaik, Casper C; Helder, Johannes; Bakker, Jaap; Goverse, Aska; Schots, Arjen; Smant, Geert

2014-12-01

Despite causing considerable damage to host tissue during the onset of parasitism, nematodes establish remarkably persistent infections in both animals and plants. It is thought that an elaborate repertoire of effector proteins in nematode secretions suppresses damage-triggered immune responses of the host. However, the nature and mode of action of most immunomodulatory compounds in nematode secretions are not well understood. Here, we show that venom allergen-like proteins of plant-parasitic nematodes selectively suppress host immunity mediated by surface-localized immune receptors. Venom allergen-like proteins are uniquely conserved in secretions of all animal- and plant-parasitic nematodes studied to date, but their role during the onset of parasitism has thus far remained elusive. Knocking-down the expression of the venom allergen-like protein Gr-VAP1 severely hampered the infectivity of the potato cyst nematode Globodera rostochiensis. By contrast, heterologous expression of Gr-VAP1 and two other venom allergen-like proteins from the beet cyst nematode Heterodera schachtii in plants resulted in the loss of basal immunity to multiple unrelated pathogens. The modulation of basal immunity by ectopic venom allergen-like proteins in Arabidopsis thaliana involved extracellular protease-based host defenses and non-photochemical quenching in chloroplasts. Non-photochemical quenching regulates the initiation of the defense-related programmed cell death, the onset of which was commonly suppressed by venom allergen-like proteins from G. rostochiensis, H. schachtii, and the root-knot nematode Meloidogyne incognita. Surprisingly, these venom allergen-like proteins only affected the programmed cell death mediated by surface-localized immune receptors. Furthermore, the delivery of venom allergen-like proteins into host tissue coincides with the enzymatic breakdown of plant cell walls by migratory nematodes. We, therefore, conclude that parasitic nematodes most likely utilize venom allergen-like proteins to suppress the activation of defenses by immunogenic breakdown products in damaged host tissue.

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 mast cell proteases. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Current European Labyrinthula zosterae Are Not Virulent and Modulate Seagrass (Zostera marina) Defense Gene Expression

PubMed Central

Brakel, Janina; Werner, Franziska Julie; Tams, Verena; Reusch, Thorsten B. H.; Bockelmann, Anna-Christina

2014-01-01

Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930's, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype×genotype interactions of host and pathogen from different regions (10–100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist×eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the host's defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence. PMID:24691450

Oral lactoferrin for the treatment of sepsis and necrotizing enterocolitis in neonates

USDA-ARS?s Scientific Manuscript database

Neonatal sepsis and necrotizing enterocolitis (NEC) cause significant neonatal mortality and morbidity in spite of appropriate antibiotic therapy. Enhancing host defense and modulating inflammation by using lactoferrin as an adjunct to antibiotics in the treatment of sepsis and/or NEC may improve cl...

Oxygen-Dependent Globin Coupled Sensor Signaling Modulates Motility and Virulence of the Plant Pathogen Pectobacterium carotovorum.

PubMed

Burns, Justin L; Jariwala, Parth B; Rivera, Shannon; Fontaine, Benjamin M; Briggs, Laura; Weinert, Emily E

2017-08-18

Bacterial pathogens utilize numerous signals to identify the presence of their host and coordinate changes in gene expression that allow for infection. Within plant pathogens, these signals typically include small molecules and/or proteins from their plant hosts and bacterial quorum sensing molecules to ensure sufficient bacterial cell density for successful infection. In addition, bacteria use environmental signals to identify conditions when the host defenses are weakened and potentially to signal entry into an appropriate host/niche for infection. A globin coupled sensor protein (GCS), termed PccGCS, within the soft rot bacterium Pectobacterium carotovorum ssp. carotovorum WPP14 has been identified as an O 2 sensor and demonstrated to alter virulence factor excretion and control motility, with deletion of PccGCS resulting in decreased rotting of a potato host. Using small molecules that modulate bacterial growth and quorum sensing, PccGCS signaling also has been shown to modulate quorum sensing pathways, resulting in the PccGCS deletion strain being more sensitive to plant-derived phenolic acids, which can function as quorum sensing inhibitors, and exhibiting increased N-acylhomoserine lactone (AHL) production. These findings highlight a role for GCS proteins in controlling key O 2 -dependent phenotypes of pathogenic bacteria and suggest that modulating GCS signaling to limit P. carotovorum motility may provide a means to decrease rotting of plant hosts.

Microbial modulation of bacoside A biosynthetic pathway and systemic defense mechanism in Bacopa monnieri under Meloidogyne incognita stress

PubMed Central

Gupta, Rupali; Singh, Akanksha; Srivastava, Madhumita; Singh, Vivek; Gupta, M. M.; Pandey, Rakesh

2017-01-01

Plant-associated beneficial microbes have been explored to fulfill the imperative function for plant health. However, their impact on the host secondary metabolite production and nematode disease management remains elusive. Our present work has shown that chitinolytic microbes viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 singly as well as in combination modulated the biosynthetic pathway of bacoside A and systemic defense mechanism against Meloidogyne incognita in Bacopa monnieri. Interestingly, expression of bacoside biosynthetic pathway genes (3-Hydroxy-3-methylglutaryl coenzyme A reductase, mevalonate diphosphate decarboxylase, and squalene synthase) were upregulated in plants treated with the microbial combination in the presence as well as in absence of M. incognita stress. These microbes not only augmented bacoside A production (1.5 fold) but also strengthened host resistance via enhancement in chlorophyll a, defense enzymes and phenolic compounds like gallic acid, syringic acid, ferulic acid and cinnamic acid. Furthermore, elevated lignification and callose deposition in the microbial combination treated plants corroborate well with the above findings. Overall, the results provide novel insights into the underlying mechanisms of priming by beneficial microbes and underscore their capacity to trigger bacoside A production in B. monnieri under biotic stress. PMID:28157221

Phytoplasma protein effector SAP11 enhances insect vector reproduction by manipulating plant development and defense hormone biosynthesis.

PubMed

Sugio, Akiko; Kingdom, Heather N; MacLean, Allyson M; Grieve, Victoria M; Hogenhout, Saskia A

2011-11-29

Phytoplasmas are insect-transmitted phytopathogenic bacteria that can alter plant morphology and the longevity and reproduction rates and behavior of their insect vectors. There are various examples of animal and plant parasites that alter the host phenotype to attract insect vectors, but it is unclear how these parasites accomplish this. We hypothesized that phytoplasmas produce effectors that modulate specific targets in their hosts leading to the changes in plant development and insect performance. Previously, we sequenced and mined the genome of Aster Yellows phytoplasma strain Witches' Broom (AY-WB) and identified 56 candidate effectors. Here, we report that the secreted AY-WB protein 11 (SAP11) effector modulates plant defense responses to the advantage of the AY-WB insect vector Macrosteles quadrilineatus. SAP11 binds and destabilizes Arabidopsis CINCINNATA (CIN)-related TEOSINTE BRANCHED1, CYCLOIDEA, PROLIFERATING CELL FACTORS 1 and 2 (TCP) transcription factors, which control plant development and promote the expression of lipoxygenase (LOX) genes involved in jasmonate (JA) synthesis. Both the Arabidopsis SAP11 lines and AY-WB-infected plants produce less JA on wounding. Furthermore, the AY-WB insect vector produces more offspring on AY-WB-infected plants, SAP11 transgenic lines, and plants impaired in CIN-TCP and JA synthesis. Thus, SAP11-mediated destabilization of CIN-TCPs leads to the down-regulation of LOX2 expression and JA synthesis and an increase in M. quadrilineatus progeny. Phytoplasmas are obligate inhabitants of their plant host and insect vectors, in which the latter transmits AY-WB to a diverse range of plant species. This finding demonstrates that pathogen effectors can reach beyond the pathogen-host interface to modulate a third organism in the biological interaction.

Pseudomonas aeruginosa Airway Infection Recruits and Modulates Neutrophilic Myeloid-Derived Suppressor Cells

PubMed Central

Öz, Hasan H.; Zhou, Benyuan; Voss, Pina; Carevic, Melanie; Schroth, Carolin; Frey, Nina; Rieber, Nikolaus; Hector, Andreas; Hartl, Dominik

2016-01-01

Pseudomonas aeruginosa is an opportunistic pathogen that causes infections mainly in patients with cystic fibrosis (CF) lung disease. Despite innate and adaptive immune responses upon infection, P. aeruginosa is capable of efficiently escaping host defenses, but the underlying immune mechanisms remain poorly understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that are functionally characterized by their potential to suppress T- and natural killer (NK)-cell responses. Here we demonstrate, using an airway in vivo infection model, that P. aeruginosa recruits and activates neutrophilic MDSCs, which functionally suppress T-cell responses. We further show that the CF gene defect (CF transmembrane conductance regulator, CFTR) modulates the functionality, but not the recruitment or generation of neutrophilic MDSCs. Collectively, we define a mechanism by which P. aeruginosa airway infection undermines host immunity by modulating neutrophilic MDSCs in vivo. PMID:27965936

A Therapeutic Potential of Animal β-hairpin Antimicrobial Peptides.

PubMed

Panteleev, Pavel V; Balandin, Sergey V; Ivanov, Vadim T; Ovchinnikova, Tatiana V

2017-01-01

Endogenous antimicrobial peptides (AMPs) are evolutionary ancient molecular factors of innate immunity that play the key role in host defense. Because of the low resistance rate, AMPs have caught extensive attention as possible alternatives to conventional antibiotics. Over the last years, it has become evident that biological functions of AMPs are beyond direct killing of microbial cells. This review focuses on a relatively small family of animal host defense peptides with the β-hairpin structure stabilized by disulfide bridges. Their small size, rigid structure, stability to proteases, and plethora of biological functions, including antibacterial, antifungal, antiviral, anticancer, endotoxin-binding, metabolism- and immune- modulating activities, make natural β-hairpin AMPs an attractive molecular basis for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

S100A12 Is Part of the Antimicrobial Network against Mycobacterium leprae in Human Macrophages.

PubMed

Realegeno, Susan; Kelly-Scumpia, Kindra M; Dang, Angeline Tilly; Lu, Jing; Teles, Rosane; Liu, Philip T; Schenk, Mirjam; Lee, Ernest Y; Schmidt, Nathan W; Wong, Gerard C L; Sarno, Euzenir N; Rea, Thomas H; Ochoa, Maria T; Pellegrini, Matteo; Modlin, Robert L

2016-06-01

Triggering antimicrobial mechanisms in macrophages infected with intracellular pathogens, such as mycobacteria, is critical to host defense against the infection. To uncover the unique and shared antimicrobial networks induced by the innate and adaptive immune systems, gene expression profiles generated by RNA sequencing (RNAseq) from human monocyte-derived macrophages (MDMs) activated with TLR2/1 ligand (TLR2/1L) or IFN-γ were analyzed. Weighed gene correlation network analysis identified modules of genes strongly correlated with TLR2/1L or IFN-γ that were linked by the "defense response" gene ontology term. The common TLR2/1L and IFN-γ inducible human macrophage host defense network contained 16 antimicrobial response genes, including S100A12, which was one of the most highly induced genes by TLR2/1L. There is limited information on the role of S100A12 in infectious disease, leading us to test the hypothesis that S100A12 contributes to host defense against mycobacterial infection in humans. We show that S100A12 is sufficient to directly kill Mycobacterium tuberculosis and Mycobacterium leprae. We also demonstrate that S100A12 is required for TLR2/1L and IFN-γ induced antimicrobial activity against M. leprae in infected macrophages. At the site of disease in leprosy, we found that S100A12 was more strongly expressed in skin lesions from tuberculoid leprosy (T-lep), the self-limiting form of the disease, compared to lepromatous leprosy (L-lep), the progressive form of the disease. These data suggest that S100A12 is part of an innate and adaptive inducible antimicrobial network that contributes to host defense against mycobacteria in infected macrophages.

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.

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.

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.

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

Innate defense regulator IDR-1018 activates human mast cells through G protein-, phospholipase C-, MAPK- and NF-ĸB-sensitive pathways.

PubMed

Yanashima, Kensuke; Chieosilapatham, Panjit; Yoshimoto, Eri; Okumura, Ko; Ogawa, Hideoki; Niyonsaba, François

2017-08-01

Host defense (antimicrobial) peptides not only display antimicrobial activities against numerous pathogens but also exert a broader spectrum of immune-modulating functions. Innate defense regulators (IDRs) are a class of host defense peptides synthetically developed from natural or endogenous cationic host defense peptides. Of the IDRs developed to date, IDR-1018 is more efficient not only in killing bacteria but also in regulating the various functions of macrophages and neutrophils and accelerating the wound healing process. Because mast cells intimately participate in wound healing and a number of host defense peptides involved in wound healing are also known to activate mast cells, this study aimed to investigate the effects of IDR-1018 on mast cell activation. Here, we showed that IDR-1018 induced the degranulation of LAD2 human mast cells and caused their production of leukotrienes, prostaglandins and various cytokines and chemokines, including granulocyte-macrophage colony-stimulating factor, interleukin-8, monocyte chemoattractant protein-1 and -3, macrophage-inflammatory protein-1α and -1β, and tumor necrosis factor-α. Furthermore, IDR-1018 increased intracellular calcium mobilization and induced mast cell chemotaxis. The mast cell activation was markedly suppressed by pertussis toxin, U-73122, U0126, SB203580, JNK inhibitor II, and NF-κB activation inhibitor II, suggesting the involvement of G-protein, phospholipase C, ERK, p38, JNK and NF-κB pathways, respectively, in IDR-1018-induced mast cell activation. Notably, we confirmed that IDR-1018 caused the phosphorylation of MAPKs and IκB. Altogether, the current study suggests a novel immunomodulatory role of IDR-1018 through its ability to recruit and activate human mast cells at the sites of inflammation and wounds. We report that IDR-1018 stimulates various functions of human mast cells. IDR-1018-induced mast cell activation is mediated through G protein, PLC, MAPK and NF-κB pathways. IDR-1018 will be a useful therapeutic agent for wound healing.

Host–Multi-Pathogen Warfare: Pathogen Interactions in Co-infected Plants

PubMed Central

Abdullah, Araz S.; Moffat, Caroline S.; Lopez-Ruiz, Francisco J.; Gibberd, Mark R.; Hamblin, John; Zerihun, Ayalsew

2017-01-01

Studies of plant–pathogen interactions have historically focused on simple models of infection involving single host-single disease systems. However, plant infections often involve multiple species and/or genotypes and exhibit complexities not captured in single host-single disease systems. Here, we review recent insights into co-infection systems focusing on the dynamics of host-multi-pathogen interactions and the implications for host susceptibility/resistance. In co-infection systems, pathogen interactions include: (i) Competition, in which competing pathogens develop physical barriers or utilize toxins to exclude competitors from resource-dense niches; (ii) Cooperation, whereby pathogens beneficially interact, by providing mutual biochemical signals essential for pathogenesis, or through functional complementation via the exchange of resources necessary for survival; (iii) Coexistence, whereby pathogens can stably coexist through niche specialization. Furthermore, hosts are also able to, actively or passively, modulate niche competition through defense responses that target at least one pathogen. Typically, however, virulent pathogens subvert host defenses to facilitate infection, and responses elicited by one pathogen may be modified in the presence of another pathogen. Evidence also exists, albeit rare, of pathogens incorporating foreign genes that broaden niche adaptation and improve virulence. Throughout this review, we draw upon examples of co-infection systems from a range of pathogen types and identify outstanding questions for future innovation in disease control strategies. PMID:29118773

Rhizobacterial colonization of roots modulates plant volatile emission and enhances the attraction of a parasitoid wasp to host-infested plants.

PubMed

Pangesti, Nurmi; Weldegergis, Berhane T; Langendorf, Benjamin; van Loon, Joop J A; Dicke, Marcel; Pineda, Ana

2015-08-01

Beneficial root-associated microbes modify the physiological status of their host plants and affect direct and indirect plant defense against insect herbivores. While the effects of these microbes on direct plant defense against insect herbivores are well described, knowledge of the effect of the microbes on indirect plant defense against insect herbivores is still limited. In this study, we evaluate the role of the rhizobacterium Pseudomonas fluorescens WCS417r in indirect plant defense against the generalist leaf-chewing insect Mamestra brassicae through a combination of behavioral, chemical, and gene-transcriptional approaches. We show that rhizobacterial colonization of Arabidopsis thaliana roots results in an increased attraction of the parasitoid Microplitis mediator to caterpillar-infested plants. Volatile analysis revealed that rhizobacterial colonization suppressed the emission of the terpene (E)-α-bergamotene and the aromatics methyl salicylate and lilial in response to caterpillar feeding. Rhizobacterial colonization decreased the caterpillar-induced transcription of the terpene synthase genes TPS03 and TPS04. Rhizobacteria enhanced both the growth and the indirect defense of plants under caterpillar attack. This study shows that rhizobacteria have a high potential to enhance the biocontrol of leaf-chewing herbivores based on enhanced attraction of parasitoids.

Hormone crosstalk in plant disease and defense: more than just jasmonate-salicylate antagonism.

PubMed

Robert-Seilaniantz, Alexandre; Grant, Murray; Jones, Jonathan D G

2011-01-01

Until recently, most studies on the role of hormones in plant-pathogen interactions focused on salicylic acid (SA), jasmonic acid (JA), and ethylene (ET). It is now clear that pathogen-induced modulation of signaling via other hormones contributes to virulence. A picture is emerging of complex crosstalk and induced hormonal changes that modulate disease and resistance, with outcomes dependent on pathogen lifestyles and the genetic constitution of the host. Recent progress has revealed intriguing similarities between hormone signaling mechanisms, with gene induction responses often achieved by derepression. Here, we report on recent advances, updating current knowledge on classical defense hormones SA, JA, and ET, and the roles of auxin, abscisic acid (ABA), cytokinins (CKs), and brassinosteroids in molding plant-pathogen interactions. We highlight an emerging theme that positive and negative regulators of these disparate hormone signaling pathways are crucial regulatory targets of hormonal crosstalk in disease and defense. Copyright © 2011 by Annual Reviews. All rights reserved.

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

PubMed Central

Chung, Seung Ho; Scully, Erin D.; Peiffer, Michelle; Geib, Scott M.; Rosa, Cristina; Hoover, Kelli; Felton, Gary W.

2017-01-01

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 previously showed that symbiotic gut bacteria from CPB larvae suppressed jasmonate (JA)-induced defenses in tomato. However, little is known about how changes in the bacterial community may be involved in the manipulation of induced defenses in wild and cultivated Solanum plants of CPB. Here, we examined suppression of JA-mediated defense in wild and cultivated hosts of CPB by chemical elicitors and their symbiotic bacteria. Furthermore, we investigated associations between the gut bacterial community and suppression of plant defenses using 16 S rRNA amplicon sequencing. Symbiotic bacteria decreased plant defenses in all Solanum hosts and there were different gut bacterial communities in CPB fed on different host plants. When larvae were reared on different hosts, defense suppression differed among host plants. These results demonstrate that host plants influence herbivore gut bacterial communities and consequently affect the herbivore’s ability to manipulate JA-mediated plant defenses. Thus, the presence of symbiotic bacteria that suppress plant defenses might help CPB adapt to host plants. PMID:28045052

Evolution of Host Defense against Multiple Enemy Populations.

PubMed

Toor, Jaspreet; Best, Alex

2016-03-01

Natural and managed populations are embedded within complex ecological communities, where they face multiple enemies. Experimental studies have shown that the evolution of host defense mechanisms to a focal enemy is impacted by the surrounding enemy community. Theoretically, the evolution of host defenses against a single enemy population, typically parasites, has been widely studied, but only recently has the impact of community interactions on host-parasite evolution been looked at. In this article, we theoretically examine the evolutionary behavior of a host population that must allocate defenses between two enemy populations, parasites and predators, with defense against one enemy constraining defense against the other. We show that in simpler models the composition of the enemy community plays the key role in determining the defense strategy of the hosts, with the hosts building up defenses against the enemy population posing a larger threat. However, this simple driver is shown to break down when there is significant recovery and reproduction from infected hosts. Additionally, we find that most host diversity is likely to occur when there is a combined high risk of infection and predation, in common with experimental studies. Our results therefore provide vital insight into the ecological feedbacks that drive the evolution of host defense against multiple enemy populations.

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

PubMed

Chung, Seung Ho; Scully, Erin D; Peiffer, Michelle; Geib, Scott M; Rosa, Cristina; Hoover, Kelli; Felton, Gary W

2017-01-03

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 previously showed that symbiotic gut bacteria from CPB larvae suppressed jasmonate (JA)-induced defenses in tomato. However, little is known about how changes in the bacterial community may be involved in the manipulation of induced defenses in wild and cultivated Solanum plants of CPB. Here, we examined suppression of JA-mediated defense in wild and cultivated hosts of CPB by chemical elicitors and their symbiotic bacteria. Furthermore, we investigated associations between the gut bacterial community and suppression of plant defenses using 16 S rRNA amplicon sequencing. Symbiotic bacteria decreased plant defenses in all Solanum hosts and there were different gut bacterial communities in CPB fed on different host plants. When larvae were reared on different hosts, defense suppression differed among host plants. These results demonstrate that host plants influence herbivore gut bacterial communities and consequently affect the herbivore's ability to manipulate JA-mediated plant defenses. Thus, the presence of symbiotic bacteria that suppress plant defenses might help CPB adapt to host plants.

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.

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 disease caused by tick-borne viruses. PMID:28798904

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 disease caused by tick-borne viruses.

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

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

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

Tamm-Horsfall glycoprotein engages human Siglec-9 to modulate neutrophil activation in the urinary tract

PubMed Central

Patras, Kathryn A.; Coady, Alison; Olson, Joshua; Ali, Syed Raza; RamachandraRao, Satish P.; Kumar, Satish; Varki, Ajit; Nizet, Victor

2017-01-01

Urinary tract infections (UTI) are a major problem in human medicine for which better understanding of native immune defenses may reveal new pathways for therapeutic intervention. Tamm-Horsfall glycoprotein (THP), the most abundant urinary protein, interacts with bacteria including uropathogenic E. coli (UPEC) as well host immune cells. In addition to its well-studied functions to antagonize bacterial colonization, we hypothesize that THP serves a critical host defense function through innate immune modulation. Using isolated human neutrophils, we found that THP binds neutrophils and that this interaction reduces reactive oxygen species generation, chemotaxis, and killing of UPEC. We discovered that THP engages the inhibitory neutrophil receptor sialic acid-binding Ig-like lectin-9 (Siglec-9), and mouse functional ortholog Siglec-E, in a manner dependent on sialic acid on its N-glycan moieties. THP-null mice have significantly more neutrophils present in the urine compared to WT mice, both with and without the presence of inflammatory stimuli. These data support THP as an important negative regulator of neutrophil activation in the urinary tract, with dual functions to counteract bacterial colonization and suppress excessive inflammation within the urinary tract. PMID:28829050

Ethylene and 1-Aminocyclopropane-1-carboxylate (ACC) in Plant–Bacterial Interactions

PubMed Central

Nascimento, Francisco X.; Rossi, Márcio J.; Glick, Bernard R.

2018-01-01

Ethylene and its precursor 1-aminocyclopropane-1-carboxylate (ACC) actively participate in plant developmental, defense and symbiotic programs. In this sense, ethylene and ACC play a central role in the regulation of bacterial colonization (rhizospheric, endophytic, and phyllospheric) by the modulation of plant immune responses and symbiotic programs, as well as by modulating several developmental processes, such as root elongation. Plant-associated bacterial communities impact plant growth and development, both negatively (pathogens) and positively (plant-growth promoting and symbiotic bacteria). Some members of the plant-associated bacterial community possess the ability to modulate plant ACC and ethylene levels and, subsequently, modify plant defense responses, symbiotic programs and overall plant development. In this work, we review and discuss the role of ethylene and ACC in several aspects of plant-bacterial interactions. Understanding the impact of ethylene and ACC in both the plant host and its associated bacterial community is key to the development of new strategies aimed at increased plant growth and protection. PMID:29520283

Innate immune interactions within the central nervous system modulate pathogenesis of viral infections

PubMed Central

Nair, Sharmila; Diamond, Michael S.

2015-01-01

The innate immune system mediates protection against neurotropic viruses that replicate in the central nervous system (CNS). Virus infection within specific cells of the CNS triggers activation of several families of pattern recognition receptors including Toll-like receptors, retinoic acid-inducible gene 1 like receptors, nucleotide-binding oligomerization domain-like receptors, and cytosolic DNA sensors. In this review, we highlight recent advances in our understanding of how cell-intrinsic host defenses within the CNS modulate infection of different DNA and RNA viruses. PMID:26163762

Cell-Specific IRF-3 Responses Protect against West Nile Virus Infection by Interferon-Dependent and -Independent Mechanisms

PubMed Central

Daffis, Stephane; Samuel, Melanie A; Keller, Brian C; Gale, Michael; Diamond, Michael S

2007-01-01

Interferon regulatory factor (IRF)-3 is a master transcription factor that activates host antiviral defense programs. Although cell culture studies suggest that IRF-3 promotes antiviral control by inducing interferon (IFN)-β, near normal levels of IFN-α and IFN-β were observed in IRF-3−/− mice after infection by several RNA and DNA viruses. Thus, the specific mechanisms by which IRF-3 modulates viral infection remain controversial. Some of this disparity could reflect direct IRF-3-dependent antiviral responses in specific cell types to control infection. To address this and determine how IRF-3 coordinates an antiviral response, we infected IRF-3−/− mice and two primary cells relevant for West Nile virus (WNV) pathogenesis, macrophages and cortical neurons. IRF-3−/− mice were uniformly vulnerable to infection and developed elevated WNV burdens in peripheral and central nervous system tissues, though peripheral IFN responses were largely normal. Whereas wild-type macrophages basally expressed key host defense molecules, including RIG-I, MDA5, ISG54, and ISG56, and restricted WNV infection, IRF-3−/− macrophages lacked basal expression of these host defense genes and supported increased WNV infection and IFN-α and IFN-β production. In contrast, wild-type cortical neurons were highly permissive to WNV and did not basally express RIG-I, MDA5, ISG54, and ISG56. IRF-3−/− neurons lacked induction of host defense genes and had blunted IFN-α and IFN-β production, yet exhibited only modestly increased viral titers. Collectively, our data suggest that cell-specific IRF-3 responses protect against WNV infection through both IFN-dependent and -independent programs. PMID:17676997

Cytokine Diedel and a viral homologue suppress the IMD pathway in Drosophila.

PubMed

Lamiable, Olivier; Kellenberger, Christine; Kemp, Cordula; Troxler, Laurent; Pelte, Nadège; Boutros, Michael; Marques, Joao Trindade; Daeffler, Laurent; Hoffmann, Jules A; Roussel, Alain; Imler, Jean-Luc

2016-01-19

Viruses are obligatory intracellular parasites that suffer strong evolutionary pressure from the host immune system. Rapidly evolving viral genomes can adapt to this pressure by acquiring genes that counteract host defense mechanisms. For example, many vertebrate DNA viruses have hijacked cellular genes encoding cytokines or cytokine receptors to disrupt host cell communication. Insect viruses express suppressors of RNA interference or apoptosis, highlighting the importance of these cell intrinsic antiviral mechanisms in invertebrates. Here, we report the identification and characterization of a family of proteins encoded by insect DNA viruses that are homologous to a 12-kDa circulating protein encoded by the virus-induced Drosophila gene diedel (die). We show that die mutant flies have shortened lifespan and succumb more rapidly than controls when infected with Sindbis virus. This reduced viability is associated with deregulated activation of the immune deficiency (IMD) pathway of host defense and can be rescued by mutations in the genes encoding the homolog of IKKγ or IMD itself. Our results reveal an endogenous pathway that is exploited by insect viruses to modulate NF-κB signaling and promote fly survival during the antiviral response.

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.

Geminiviruses and Plant Hosts: A Closer Examination of the Molecular Arms Race.

PubMed

Ramesh, Shunmugiah V; Sahu, Pranav P; Prasad, Manoj; Praveen, Shelly; Pappu, Hanu R

2017-09-15

Geminiviruses are plant-infecting viruses characterized by a single-stranded DNA (ssDNA) genome. Geminivirus-derived proteins are multifunctional and effective regulators in modulating the host cellular processes resulting in successful infection. Virus-host interactions result in changes in host gene expression patterns, reprogram plant signaling controls, disrupt central cellular metabolic pathways, impair plant's defense system, and effectively evade RNA silencing response leading to host susceptibility. This review summarizes what is known about the cellular processes in the continuing tug of war between geminiviruses and their plant hosts at the molecular level. In addition, implications for engineered resistance to geminivirus infection in the context of a greater understanding of the molecular processes are also discussed. Finally, the prospect of employing geminivirus-based vectors in plant genome engineering and the emergence of powerful genome editing tools to confer geminivirus resistance are highlighted to complete the perspective on geminivirus-plant molecular interactions.

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.

Geminiviruses and Plant Hosts: A Closer Examination of the Molecular Arms Race

PubMed Central

Ramesh, Shunmugiah V.; Sahu, Pranav P.; Prasad, Manoj; Praveen, Shelly; Pappu, Hanu R.

2017-01-01

Geminiviruses are plant-infecting viruses characterized by a single-stranded DNA (ssDNA) genome. Geminivirus-derived proteins are multifunctional and effective regulators in modulating the host cellular processes resulting in successful infection. Virus-host interactions result in changes in host gene expression patterns, reprogram plant signaling controls, disrupt central cellular metabolic pathways, impair plant’s defense system, and effectively evade RNA silencing response leading to host susceptibility. This review summarizes what is known about the cellular processes in the continuing tug of war between geminiviruses and their plant hosts at the molecular level. In addition, implications for engineered resistance to geminivirus infection in the context of a greater understanding of the molecular processes are also discussed. Finally, the prospect of employing geminivirus-based vectors in plant genome engineering and the emergence of powerful genome editing tools to confer geminivirus resistance are highlighted to complete the perspective on geminivirus-plant molecular interactions. PMID:28914771

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.

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 plant response. Indeed, several putative effector genes are among the highest expressed genes in planta.

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.

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.

Ticks and Tick-Borne Infections: Complex Ecology, Agents, and Host Interactions.

PubMed

Wikel, Stephen K

2018-06-20

Ticks transmit the most diverse array of infectious agents of any arthropod vector. Both ticks and the microbes they transmit are recognized as significant threats to human and veterinary public health. This article examines the potential impacts of climate change on the distribution of ticks and the infections they transmit; the emergence of novel tick-borne pathogens, increasing geographic range and incidence of tick-borne infections; and advances in the characterization of tick saliva mediated modulation of host defenses and the implications of those interactions for transmission, establishment, and control of tick infestation and tick-borne infectious agents.

Adaptive evolution has targeted the C-terminal domain of the RXLR effectors of plant pathogenic oomycetes.

PubMed

Win, Joe; Kamoun, Sophien

2008-04-01

Plant pathogenic microbes deliver effector proteins inside host cells to modulate plant defense circuitry and enable parasitic colonization. As genome sequences from plant pathogens become available, genome-wide evolutionary analyses will shed light on how pathogen effector genes evolved and adapted to the cellular environment of their host plants. In the August 2007 issue of Plant Cell, we described adaptive evolution (positive selection) in the cytoplasmic RXLR effectors of three recently sequenced oomycete plant pathogens. Here, we summarize our findings and describe additional data that further validate our approach.

Modulation of Ocular Inflammation by Mesenchymal Stem Cells

DTIC Science & Technology

2017-03-01

mature myeloid cells in 64 host defense and resolution of inflammation, excessive innate immune response can have 65 deleterious effects on tissue...that MSCs can regulate 69 functions of mature innate immune cells , including polarization of inflammatory macrophages 70 into an anti-inflammatory... cells 191 As immune cells are primarily developed in lymphoid organs, single cell suspensions from bone 192 marrow, spleen, and submandibular lymph

Coevolutionary arms race versus host defense chase in a tropical herbivore-plant system.

PubMed

Endara, María-José; Coley, Phyllis D; Ghabash, Gabrielle; Nicholls, James A; Dexter, Kyle G; Donoso, David A; Stone, Graham N; Pennington, R Toby; Kursar, Thomas A

2017-09-05

Coevolutionary models suggest that herbivores drive diversification and community composition in plants. For herbivores, many questions remain regarding how plant defenses shape host choice and community structure. We addressed these questions using the tree genus Inga and its lepidopteran herbivores in the Amazon. We constructed phylogenies for both plants and insects and quantified host associations and plant defenses. We found that similarity in herbivore assemblages between Inga species was correlated with similarity in defenses. There was no correlation with phylogeny, a result consistent with our observations that the expression of defenses in Inga is independent of phylogeny. Furthermore, host defensive traits explained 40% of herbivore community similarity. Analyses at finer taxonomic scales showed that different lepidopteran clades select hosts based on different defenses, suggesting taxon-specific histories of herbivore-host plant interactions. Finally, we compared the phylogeny and defenses of Inga to phylogenies for the major lepidopteran clades. We found that closely related herbivores fed on Inga with similar defenses rather than on closely related plants. Together, these results suggest that plant defenses might be more evolutionarily labile than the herbivore traits related to host association. Hence, there is an apparent asymmetry in the evolutionary interactions between Inga and its herbivores. Although plants may evolve under selection by herbivores, we hypothesize that herbivores may not show coevolutionary adaptations, but instead "chase" hosts based on the herbivore's own traits at the time that they encounter a new host, a pattern more consistent with resource tracking than with the arms race model of coevolution.

Coevolutionary arms race versus host defense chase in a tropical herbivore–plant system

PubMed Central

Coley, Phyllis D.; Ghabash, Gabrielle; Nicholls, James A.; Donoso, David A.; Stone, Graham N.; Pennington, R. Toby; Kursar, Thomas A.

2017-01-01

Coevolutionary models suggest that herbivores drive diversification and community composition in plants. For herbivores, many questions remain regarding how plant defenses shape host choice and community structure. We addressed these questions using the tree genus Inga and its lepidopteran herbivores in the Amazon. We constructed phylogenies for both plants and insects and quantified host associations and plant defenses. We found that similarity in herbivore assemblages between Inga species was correlated with similarity in defenses. There was no correlation with phylogeny, a result consistent with our observations that the expression of defenses in Inga is independent of phylogeny. Furthermore, host defensive traits explained 40% of herbivore community similarity. Analyses at finer taxonomic scales showed that different lepidopteran clades select hosts based on different defenses, suggesting taxon-specific histories of herbivore–host plant interactions. Finally, we compared the phylogeny and defenses of Inga to phylogenies for the major lepidopteran clades. We found that closely related herbivores fed on Inga with similar defenses rather than on closely related plants. Together, these results suggest that plant defenses might be more evolutionarily labile than the herbivore traits related to host association. Hence, there is an apparent asymmetry in the evolutionary interactions between Inga and its herbivores. Although plants may evolve under selection by herbivores, we hypothesize that herbivores may not show coevolutionary adaptations, but instead “chase” hosts based on the herbivore’s own traits at the time that they encounter a new host, a pattern more consistent with resource tracking than with the arms race model of coevolution. PMID:28827317

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

Suppression of RNA Silencing by a Plant DNA Virus Satellite Requires a Host Calmodulin-Like Protein to Repress RDR6 Expression

PubMed Central

Li, Fangfang; Huang, Changjun; Li, Zhenghe; Zhou, Xueping

2014-01-01

In plants, RNA silencing plays a key role in antiviral defense. To counteract host defense, plant viruses encode viral suppressors of RNA silencing (VSRs) that target different effector molecules in the RNA silencing pathway. Evidence has shown that plants also encode endogenous suppressors of RNA silencing (ESRs) that function in proper regulation of RNA silencing. The possibility that these cellular proteins can be subverted by viruses to thwart host defense is intriguing but has not been fully explored. Here we report that the Nicotiana benthamiana calmodulin-like protein Nbrgs-CaM is required for the functions of the VSR βC1, the sole protein encoded by the DNA satellite associated with the geminivirus Tomato yellow leaf curl China virus (TYLCCNV). Nbrgs-CaM expression is up-regulated by the βC1. Transgenic plants over-expressing Nbrgs-CaM displayed developmental abnormities reminiscent of βC1-associated morphological alterations. Nbrgs-CaM suppressed RNA silencing in an Agrobacterium infiltration assay and, when over-expressed, blocked TYLCCNV-induced gene silencing. Genetic evidence showed that Nbrgs-CaM mediated the βC1 functions in silencing suppression and symptom modulation, and was required for efficient virus infection. Moreover, the tobacco and tomato orthologs of Nbrgs-CaM also possessed ESR activity, and were induced by betasatellite to promote virus infection in these Solanaceae hosts. We further demonstrated that βC1-induced Nbrgs-CaM suppressed the production of secondary siRNAs, likely through repressing RNA-DEPENDENT RNA POLYMERASE 6 (RDR6) expression. RDR6-deficient N. benthamiana plants were defective in antiviral response and were hypersensitive to TYLCCNV infection. More significantly, TYLCCNV could overcome host range restrictions to infect Arabidopsis thaliana when the plants carried a RDR6 mutation. These findings demonstrate a distinct mechanism of VSR for suppressing PTGS through usurpation of a host ESR, and highlight an essential role for RDR6 in RNA silencing defense response against geminivirus infection. PMID:24516387

Leaf-mining by Phyllonorycter blancardella reprograms the host-leaf transcriptome to modulate phytohormones associated with nutrient mobilization and plant defense.

PubMed

Zhang, Hui; Dugé de Bernonville, Thomas; Body, Mélanie; Glevarec, Gaëlle; Reichelt, Michael; Unsicker, Sybille; Bruneau, Maryline; Renou, Jean-Pierre; Huguet, Elisabeth; Dubreuil, Géraldine; Giron, David

2016-01-01

Phytohormones have long been hypothesized to play a key role in the interactions between plant-manipulating organisms and their host-plants such as insect-plant interactions that lead to gall or 'green-islands' induction. However, mechanistic understanding of how phytohormones operate in these plant reconfigurations is lacking due to limited information on the molecular and biochemical phytohormonal modulation following attack by plant-manipulating insects. In an attempt to fill this gap, the present study provides an extensive characterization of how the leaf-miner Phyllonorycter blancardella modulates the major phytohormones and the transcriptional activity of plant cells in leaves of Malus domestica. We show here, that cytokinins strongly accumulate in mined tissues despite a weak expression of plant cytokinin-related genes. Leaf-mining is also associated with enhanced biosynthesis of jasmonic acid precursors but not the active form, a weak alteration of the salicylic acid pathway and a clear inhibition of the abscisic acid pathway. Our study consolidates previous results suggesting that insects may produce and deliver cytokinins to the plant as a strategy to manipulate the physiology of the leaf to create a favorable nutritional environment. We also demonstrate that leaf-mining by P. blancardella leads to a strong reprogramming of the plant phytohormonal balance associated with increased nutrient mobilization, inhibition of leaf senescence and mitigation of plant direct and indirect defense. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emerging Role of D-Amino Acid Metabolism in the Innate Defense

PubMed Central

Sasabe, Jumpei; Suzuki, Masataka

2018-01-01

Mammalian innate and adaptive immune systems use the pattern recognition receptors, such as toll-like receptors, to detect conserved bacterial and viral components. Bacteria synthesize diverse D-amino acids while eukaryotes and archaea generally produce two D-amino acids, raising the possibility that many of bacterial D-amino acids are bacteria-specific metabolites. Although D-amino acids have not been identified to bind to any known pattern recognition receptors, D-amino acids are enantioselectively recognized by some other receptors and enzymes including a flavoenzyme D-amino acid oxidase (DAO) in mammals. At host–microbe interfaces in the neutrophils and intestinal mucosa, DAO catalyzes oxidation of bacterial D-amino acids, such as D-alanine, and generates H2O2, which is linked to antimicrobial activity. Intestinal DAO also modifies the composition of microbiota through modulation of growth for some bacteria that are dependent on host nutrition. Furthermore, regulation and recognition of D-amino acids in mammals have additional meanings at various host–microbe interfaces; D-phenylalanine and D-tryptophan regulate chemotaxis of neutrophils through a G-coupled protein receptor, D-serine has a bacteriostatic role in the urinary tract, D-phenylalanine and D-leucine inhibit innate immunity through the sweet taste receptor in the upper airway, and D-tryptophan modulates immune tolerance in the lower airway. This mini-review highlights recent evidence supporting the hypothesis that D-amino acids are utilized as inter-kingdom communication at host–microbe interface to modulate bacterial colonization and host defense. PMID:29867842

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

PubMed

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

2011-07-29

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

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

Inducible MicroRNA-3570 Feedback Inhibits the RIG-I-Dependent Innate Immune Response to Rhabdovirus in Teleost Fish by Targeting MAVS/IPS-1.

PubMed

Xu, Tianjun; Chu, Qing; Cui, Junxia; Bi, Dekun

2018-01-15

Effectively recognizing invading viruses and subsequently inducing innate antiviral immunity are essential for host antiviral defense. Although these processes are closely regulated by the host to maintain immune balance, viruses have evolved the ability to downregulate or upregulate these processes for their survival. MicroRNAs (miRNAs) are a family of small noncoding RNAs that play vital roles in modulating host immune response. Accumulating evidence demonstrates that host miRNAs as mediators are involved in regulating viral replication and host antiviral immunity in mammals. However, the underlying regulatory mechanisms in fish species are still poorly understood. Here, we found that rhabdovirus infection significantly upregulated host miR-3570 expression in miiuy croaker macrophages. Induced miR-3570 negatively modulated RNA virus-triggered type I interferon (IFN) and antiviral gene production, thus facilitating viral replication. Furthermore, miR-3570 was found to target and posttranscriptionally downregulate mitochondrial antiviral signaling protein (MAVS), which functions as a platform for innate antiviral signal transduction. Moreover, we demonstrated that miR-3570 suppressed the expression of MAVS, thereby inhibiting MAVS-mediated NF-κB and IRF3 signaling. The collective results demonstrated a novel regulation mechanism of MAVS-mediated immunity during RNA viral infection by miRNA. IMPORTANCE RNA viral infection could upregulate host miR-3570 expression in miiuy croaker macrophages. Induced miR-3570 negatively modulates RNA virus-triggered type I IFN and antiviral gene production, thus facilitating viral replication. Remarkably, miR-3570 could target and inhibit MAVS expression, which thus modulates MAVS-mediated NF-κB and IRF3 signaling. The collective results of this study suggest a novel regulation mechanism of MAVS-mediated immunity during RNA viral infection by miR-3570. Thus, a novel mechanism for virus evasion in fish is proposed. Copyright © 2018 American Society for Microbiology.

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.

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.

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.

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.

Sensing Danger: Key to Activating Plant Immunity.

PubMed

Gust, Andrea A; Pruitt, Rory; Nürnberger, Thorsten

2017-09-01

In both plants and animals, defense against pathogens relies on a complex surveillance system for signs of danger. Danger signals may originate from the infectious agent or from the host itself. Immunogenic plant host factors can be roughly divided into two categories: molecules which are passively released upon cell damage ('classical' damage-associated molecular patterns, DAMPs), and peptides which are processed and/or secreted upon infection to modulate the immune response (phytocytokines). We highlight the ongoing challenge to understand how plants sense various danger signals and integrate this information to produce an appropriate immune response to diverse challenges. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems.

PubMed

Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C; Fire, Andrew Z; Sánchez-Amat, Antonio

2017-08-17

CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea . One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an 'arms race' in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems.

Kupffer cell complement receptor clearance function and host defense.

PubMed

Loegering, D J

1986-01-01

Kupffer cells are well known to be important for normal host defense function. The development of methods to evaluate the in vivo function of specific receptors on Kupffer cells has made it possible to assess the role of these receptors in host defense. The rationale for studying complement receptors is based on the proposed important role of these receptors in host defense and on the observation that the hereditary deficiency of a complement receptor is associated with recurrent severe bacterial infections. The studies reviewed here demonstrate that forms of injury that are associated with depressed host defense including thermal injury, hemorrhagic shock, trauma, and surgery also cause a decrease in complement receptor clearance function. This decrease in Kupffer cell receptor clearance function was shown not to be the result of depressed hepatic blood flow or depletion of complement components. Complement receptor function was also depressed following the phagocytosis of particulates that are known to depress Kupffer cell host defense function. Endotoxemia and bacteremia also were associated with a depression of complement receptor function. Complement receptor function was experimentally depressed in uninjured animals by the phagocytosis of IgG-coated erythrocytes. There was a close association between the depression of complement receptor clearance function and increased susceptibility to the lethal effects of endotoxin and bacterial infection. These studies support the hypotheses that complement receptors on Kupffer cells are important for normal host defense and that depression of the function of these receptors impairs host defense.

Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation

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

Hyde, Jennifer L.; Diamond, Michael S., E-mail: diamond@borcim.wustl.edu; Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110

N-7 and 2′-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m{sup 7}GpppN; cap 1, m{sup 7}GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2′-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on theirmore » RNA through cap-snatching or virally-encoded 2′-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5′-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.« less

Food-mediated modulation of immunity in a phytophagous insect: An effect of nutrition rather than parasitic contamination.

PubMed

Vogelweith, Fanny; Moreau, Jérôme; Thiéry, Denis; Moret, Yannick

2015-06-01

Inherent to the cost of immunity, the immune system itself can exhibit tradeoffs between its arms. Phytophagous insects face a wide range of microbial and eukaryotic parasites, each activating different immune pathways that could compromise the activity of the others. Feeding larvae are primarily exposed to microbes, which growth is controlled by antibiotic secondary metabolites produced by the host plant. The resulting variation in abundance of microbes on plants is expected to differentially stimulate the insect antimicrobial immune defenses. Under the above tradeoff hypothesis, stimulation of the insect antimicrobial defenses is expected to compromise immune activity against eukaryote parasites. In the European grape berry moth, Eupoecilia ambiguella, immune effectors directed towards microbes are negatively correlated to those directed towards eukaryotic parasites among host plants. Here, we hypothesize this relationship is caused by a variable control of the microbial community among host plants by their antibiotic metabolites. To test this hypothesis, we first quantified antimicrobial activity in berries of several grape varieties. We then measured immune defenses of E. ambiguella larvae raised on artificial diets in which we mimicked levels of antimicrobial activity of grape berries using tetracycline to control the abundance of growing microbes. Another group of larvae was raised on artificial diets made of berry extracts only to control for the effect of nutrition. We found that controlling microbe abundance with tetracycline in diets did not explain variation in the immune function whereas the presence of berry extracts did. This suggests that variation in immune defenses of E. ambiguella among grape varieties is caused by nutritional difference among host plants rather than microbe abundance. Further study of the effects of berry compounds on larval immune parameters will be needed to explain the observed tradeoff among immune system components. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunobiotics for the Bovine Host: Their Interaction with Intestinal Epithelial Cells and Their Effect on Antiviral Immunity

PubMed Central

Villena, Julio; Aso, Hisashi; Rutten, Victor P. M. G.; Takahashi, Hideki; van Eden, Willem; Kitazawa, Haruki

2018-01-01

The scientific community has reported several cases of microbes that exhibit elevated rates of antibiotic resistance in different regions of the planet. Due to this emergence of antimicrobial resistant microorganisms, the use of antibiotics as promoters of livestock animals’ growth is being banned in most countries around the world. One of the challenges of agricultural immunology therefore is to find alternatives by modulating the immune system of animals in drug-independent safe food production systems. In this regard, in an effort to supplant antibiotics from bovine feeds, several alternatives were proposed including the use of immunomodulatory probiotics (immunobiotics). The purpose of this review is to provide an update of the status of the modulation of intestinal antiviral innate immunity of the bovine host by immunobiotics, and the beneficial impact of immunobiotics on viral infections, focused on intestinal epithelial cells (IECs). The results of our group, which demonstrate the capacity of immunobiotic strains to beneficially modulate Toll-like receptor 3-triggered immune responses in bovine IECs and improve the resistance to viral infections, are highlighted. This review provides comprehensive information on the innate immune response of bovine IECs against virus, which can be further investigated for the development of strategies aimed to improve defenses in the bovine host. PMID:29599767

The wheat ethylene response factor transcription factor pathogen-induced ERF1 mediates host responses to both the necrotrophic pathogen Rhizoctonia cerealis and freezing stresses.

PubMed

Zhu, Xiuliang; Qi, Lin; Liu, Xin; Cai, Shibin; Xu, Huijun; Huang, Rongfeng; Li, Jiarui; Wei, Xuening; Zhang, Zengyan

2014-03-01

Sharp eyespot disease (primarily caused by the pathogen Rhizoctonia cerealis) and freezing stress are important yield limitations for the production of wheat (Triticum aestivum). Here, we report new insights into the function and underlying mechanisms of an ethylene response factor (ERF) in wheat, Pathogen-Induced ERF1 (TaPIE1), in host responses to R. cerealis and freezing stresses. TaPIE1-overexpressing transgenic wheat exhibited significantly enhanced resistance to both R. cerealis and freezing stresses, whereas TaPIE1-underexpressing wheat plants were more susceptible to both stresses relative to control plants. Following both stress treatments, electrolyte leakage and hydrogen peroxide content were significantly reduced, and both proline and soluble sugar contents were elevated in TaPIE1-overexpressing wheat, whereas these physiological traits in TaPIE1-underexpressing wheat exhibited the opposite trend. Microarray and quantitative reverse transcription-polymerase chain reaction analyses of TaPIE1-overexpressing and -underexpressing wheat plants indicated that TaPIE1 activated a subset of defense- and stress-related genes. Assays of DNA binding by electrophoretic mobility shift and transient expression in tobacco (Nicotiana tabacum) showed that the GCC boxes in the promoters of TaPIE1-activated genes were essential for transactivation by TaPIE1. The transactivation activity of TaPIE1 and the expression of TaPIE1-activated defense- and stress-related genes were significantly elevated following R. cerealis, freezing, and exogenous ethylene treatments. TaPIE1-mediated responses to R. cerealis and freezing were positively modulated by ethylene biosynthesis. These data suggest that TaPIE1 positively regulates the defense responses to R. cerealis and freezing stresses by activating defense- and stress-related genes downstream of the ethylene signaling pathway and by modulating related physiological traits in wheat.

The Wheat Ethylene Response Factor Transcription Factor PATHOGEN-INDUCED ERF1 Mediates Host Responses to Both the Necrotrophic Pathogen Rhizoctonia cerealis and Freezing Stresses1[C][W][OPEN

PubMed Central

Zhu, Xiuliang; Qi, Lin; Liu, Xin; Cai, Shibin; Xu, Huijun; Huang, Rongfeng; Li, Jiarui; Wei, Xuening; Zhang, Zengyan

2014-01-01

Sharp eyespot disease (primarily caused by the pathogen Rhizoctonia cerealis) and freezing stress are important yield limitations for the production of wheat (Triticum aestivum). Here, we report new insights into the function and underlying mechanisms of an ethylene response factor (ERF) in wheat, Pathogen-Induced ERF1 (TaPIE1), in host responses to R. cerealis and freezing stresses. TaPIE1-overexpressing transgenic wheat exhibited significantly enhanced resistance to both R. cerealis and freezing stresses, whereas TaPIE1-underexpressing wheat plants were more susceptible to both stresses relative to control plants. Following both stress treatments, electrolyte leakage and hydrogen peroxide content were significantly reduced, and both proline and soluble sugar contents were elevated in TaPIE1-overexpressing wheat, whereas these physiological traits in TaPIE1-underexpressing wheat exhibited the opposite trend. Microarray and quantitative reverse transcription-polymerase chain reaction analyses of TaPIE1-overexpressing and -underexpressing wheat plants indicated that TaPIE1 activated a subset of defense- and stress-related genes. Assays of DNA binding by electrophoretic mobility shift and transient expression in tobacco (Nicotiana tabacum) showed that the GCC boxes in the promoters of TaPIE1-activated genes were essential for transactivation by TaPIE1. The transactivation activity of TaPIE1 and the expression of TaPIE1-activated defense- and stress-related genes were significantly elevated following R. cerealis, freezing, and exogenous ethylene treatments. TaPIE1-mediated responses to R. cerealis and freezing were positively modulated by ethylene biosynthesis. These data suggest that TaPIE1 positively regulates the defense responses to R. cerealis and freezing stresses by activating defense- and stress-related genes downstream of the ethylene signaling pathway and by modulating related physiological traits in wheat. PMID:24424323

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

Proteomic Analysis of Cattle Tick Rhipicephalus (Boophilus) microplus Saliva: A Comparison between Partially and Fully Engorged Females

PubMed Central

Terra, Renata Maria Soares; Martins, João Ricardo; Mulenga, Albert; Sherman, Nicholas E.; Fox, Jay W.; Yates, John R.; Termignoni, Carlos; Pinto, Antônio F. M.; da Silva Vaz, Itabajara

2014-01-01

The cattle tick Rhipicephalus (Boophilus) microplus is one of the most harmful parasites affecting bovines. Similarly to other hematophagous ectoparasites, R. microplus saliva contains a collection of bioactive compounds that inhibit host defenses against tick feeding activity. Thus, the study of tick salivary components offers opportunities for the development of immunological based tick control methods and medicinal applications. So far, only a few proteins have been identified in cattle tick saliva. The aim of this work was to identify proteins present in R. microplus female tick saliva at different feeding stages. Proteomic analysis of R. microplus saliva allowed identifying peptides corresponding to 187 and 68 tick and bovine proteins, respectively. Our data confirm that (i) R. microplus saliva is complex, and (ii) that there are remarkable differences in saliva composition between partially engorged and fully engorged female ticks. R. microplus saliva is rich mainly in (i) hemelipoproteins and other transporter proteins, (ii) secreted cross-tick species conserved proteins, (iii) lipocalins, (iv) peptidase inhibitors, (v) antimicrobial peptides, (vii) glycine-rich proteins, (viii) housekeeping proteins and (ix) host proteins. This investigation represents the first proteomic study about R. microplus saliva, and reports the most comprehensive Ixodidae tick saliva proteome published to date. Our results improve the understanding of tick salivary modulators of host defense to tick feeding, and provide novel information on the tick-host relationship. PMID:24762651

Identification of putative TAL effector targets of the citrus canker pathogens shows functional convergence underlying disease development and defense response

PubMed Central

2014-01-01

Background Transcriptional activator-like (TAL) effectors, formerly known as the AvrBs3/PthA protein family, are DNA-binding effectors broadly found in Xanthomonas spp. that transactivate host genes upon injection via the bacterial type three-secretion system. Biologically relevant targets of TAL effectors, i.e. host genes whose induction is vital to establish a compatible interaction, have been reported for xanthomonads that colonize rice and pepper; however, citrus genes modulated by the TAL effectors PthA“s” and PthC“s” of the citrus canker bacteria Xanthomonas citri (Xc) and Xanthomonas aurantifolii pathotype C (XaC), respectively, are poorly characterized. Of particular interest, XaC causes canker disease in its host lemon (Citrus aurantifolia), but triggers a defense response in sweet orange. Results Based on, 1) the TAL effector-DNA binding code, 2) gene expression data of Xc and XaC-infiltrated sweet orange leaves, and 3) citrus hypocotyls transformed with PthA2, PthA4 or PthC1, we have identified a collection of Citrus sinensis genes potentially targeted by Xc and XaC TAL effectors. Our results suggest that similar with other strains of Xanthomonas TAL effectors, PthA2 and PthA4, and PthC1 to some extent, functionally converge. In particular, towards induction of genes involved in the auxin and gibberellin synthesis and response, cell division, and defense response. We also present evidence indicating that the TAL effectors act as transcriptional repressors and that the best scoring predicted DNA targets of PthA“s” and PthC“s” in citrus promoters predominantly overlap with or localize near to TATA boxes of core promoters, supporting the idea that TAL effectors interact with the host basal transcriptional machinery to recruit the RNA pol II and start transcription. Conclusions The identification of PthA“s” and PthC“s” targets, such as the LOB (LATERAL ORGAN BOUNDARY) and CCNBS genes that we report here, is key for the understanding of the canker symptoms development during host susceptibility, or the defenses of sweet orange against the canker bacteria. We have narrowed down candidate targets to a few, which pointed out the host metabolic pathways explored by the pathogens. PMID:24564253

Identification of putative TAL effector targets of the citrus canker pathogens shows functional convergence underlying disease development and defense response.

PubMed

Pereira, Andre L A; Carazzolle, Marcelo F; Abe, Valeria Y; de Oliveira, Maria L P; Domingues, Mariane N; Silva, Jaqueline C; Cernadas, Raul A; Benedetti, Celso E

2014-02-25

Transcriptional activator-like (TAL) effectors, formerly known as the AvrBs3/PthA protein family, are DNA-binding effectors broadly found in Xanthomonas spp. that transactivate host genes upon injection via the bacterial type three-secretion system. Biologically relevant targets of TAL effectors, i.e. host genes whose induction is vital to establish a compatible interaction, have been reported for xanthomonads that colonize rice and pepper; however, citrus genes modulated by the TAL effectors PthA"s" and PthC"s" of the citrus canker bacteria Xanthomonas citri (Xc) and Xanthomonas aurantifolii pathotype C (XaC), respectively, are poorly characterized. Of particular interest, XaC causes canker disease in its host lemon (Citrus aurantifolia), but triggers a defense response in sweet orange. Based on, 1) the TAL effector-DNA binding code, 2) gene expression data of Xc and XaC-infiltrated sweet orange leaves, and 3) citrus hypocotyls transformed with PthA2, PthA4 or PthC1, we have identified a collection of Citrus sinensis genes potentially targeted by Xc and XaC TAL effectors. Our results suggest that similar with other strains of Xanthomonas TAL effectors, PthA2 and PthA4, and PthC1 to some extent, functionally converge. In particular, towards induction of genes involved in the auxin and gibberellin synthesis and response, cell division, and defense response. We also present evidence indicating that the TAL effectors act as transcriptional repressors and that the best scoring predicted DNA targets of PthA"s" and PthC"s" in citrus promoters predominantly overlap with or localize near to TATA boxes of core promoters, supporting the idea that TAL effectors interact with the host basal transcriptional machinery to recruit the RNA pol II and start transcription. The identification of PthA"s" and PthC"s" targets, such as the LOB (lateral organ boundary) and CCNBS genes that we report here, is key for the understanding of the canker symptoms development during host susceptibility, or the defenses of sweet orange against the canker bacteria. We have narrowed down candidate targets to a few, which pointed out the host metabolic pathways explored by the pathogens.

Modulation of immune responses of Rhynchophorus ferrugineus (Insecta: Coleoptera) induced by the entomopathogenic nematode Steinernema carpocapsae (Nematoda: Rhabditida).

PubMed

Mastore, Maristella; Arizza, Vincenzo; Manachini, Barbara; Brivio, Maurizio F

2015-12-01

Aim of this study was to investigate relationships between the red palm weevil (RPW) Rhynchophorus ferrugineus (Olivier) and the entomopathogenic nematode Steinernema carpocapsae (EPN); particularly, the work was focused on the immune response of the insect host in naive larvae and after infection with the EPN. Two main immunological processes have been addressed: the activity and modulation of host prophenoloxidase-phenoloxidase (proPO) system, involved in melanization of not-self and hemocytes recognition processes responsible for not-self encapsulation. Moreover, immune depressive and immune evasive strategies of the parasite have been investigated. Our results suggest that RPW possess an efficient immune system, however in the early phase of infection, S. carpocapsae induces a strong inhibition of the host proPO system. In addition, host cell-mediated mechanisms of encapsulation, are completely avoided by the parasite, the elusive strategies of S. carpocapsae seem to be related to the structure of its body-surface, since induced alterations of the parasite cuticle resulted in the loss of its mimetic properties. S. carpocapsae before the release of its symbiotic bacteria, depress and elude RPW immune defenses, with the aim to arrange a favorable environment for its bacteria responsible of the septicemic death of the insect target. © 2014 Institute of Zoology, Chinese Academy of Sciences.

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

Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model.

PubMed

Ngba Essebe, Christelle; Visvikis, Orane; Fines-Guyon, Marguerite; Vergne, Anne; Cattoir, Vincent; Lecoustumier, Alain; Lemichez, Emmanuel; Sotto, Albert; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

2017-01-01

Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications. Staphylococcus aureus is the most prevalent pathogen isolated. Its association with Helcococcus kunzii , commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both H. kunzii and S. aureus strains in a Caenorhabditis elegans model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that H. kunzii strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast, S. aureus strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all H. kunzii ( P < 0.001). When H. kunzii and S. aureus strains were associated, H. kunzii significantly reduced the virulence of the S. aureus strain in nematodes (LT50 between 4.4 and 5.2 days; P < 0.001). To evaluate the impact of these strains on host response, transcriptomic analysis showed that the ingestion of S. aureus led to a strong induction of defense genes ( lys-5, sodh-1 , and cyp-37B1 ) while H. kunzii did not. No statistical difference of host response genes expression was observed when C. elegans were infected with either S. aureus alone or with S. aureus + H. kunzii . Moreover, two well-characterized virulence factors ( hla and agr ) present in S. aureus were down-regulated when S. aureus were co-infected with H. kunzii . This study showed that H. kunzii decreased the virulence of S. aureus without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated.

Decrease of Staphylococcus aureus Virulence by Helcococcus kunzii in a Caenorhabditis elegans Model

PubMed Central

Ngba Essebe, Christelle; Visvikis, Orane; Fines-Guyon, Marguerite; Vergne, Anne; Cattoir, Vincent; Lecoustumier, Alain; Lemichez, Emmanuel; Sotto, Albert; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

2017-01-01

Social bacterial interactions are considered essential in numerous infectious diseases, particularly in wounds. Foot ulcers are a common complication in diabetic patients and these ulcers become frequently infected. This infection is usually polymicrobial promoting cell-to-cell communications. Staphylococcus aureus is the most prevalent pathogen isolated. Its association with Helcococcus kunzii, commensal Gram-positive cocci, is frequently described. The aim of this study was to assess the impact of co-infection on virulence of both H. kunzii and S. aureus strains in a Caenorhabditis elegans model. To study the host response, qRT-PCRs targeting host defense genes were performed. We observed that H. kunzii strains harbored a very low (LT50: 5.7 days ± 0.4) or an absence of virulence (LT50: 6.9 days ± 0.5). In contrast, S. aureus strains (LT50: 2.9 days ± 0.4) were significantly more virulent than all H. kunzii (P < 0.001). When H. kunzii and S. aureus strains were associated, H. kunzii significantly reduced the virulence of the S. aureus strain in nematodes (LT50 between 4.4 and 5.2 days; P < 0.001). To evaluate the impact of these strains on host response, transcriptomic analysis showed that the ingestion of S. aureus led to a strong induction of defense genes (lys-5, sodh-1, and cyp-37B1) while H. kunzii did not. No statistical difference of host response genes expression was observed when C. elegans were infected with either S. aureus alone or with S. aureus + H. kunzii. Moreover, two well-characterized virulence factors (hla and agr) present in S. aureus were down-regulated when S. aureus were co-infected with H. kunzii. This study showed that H. kunzii decreased the virulence of S. aureus without modifying directly the host defense response. Factor(s) produced by this bacterium modulating the staphylococci virulence must be investigated. PMID:28361041

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.

Differences in the number of hemocytes in the snail host Biomphalaria tenagophila, resistant and susceptible to Schistosoma mansoni infection.

PubMed

Oliveira, A L D; Levada, P M; Zanotti-Magalhaes, E M; Magalhães, L A; Ribeiro-Paes, J T

2010-12-21

The relationships between schistosomiasis and its intermediate host, mollusks of the genus Biomphalaria, have been a concern for decades. It is known that the vector mollusk shows different susceptibility against parasite infection, whose occurrence depends on the interaction between the forms of trematode larvae and the host defense cells. These cells are called amebocytes or hemocytes and are responsible for the recognition of foreign bodies and for phagocytosis and cytotoxic reactions. The defense cells mediate the modulation of the resistant and susceptible phenotypes of the mollusk. Two main types of hemocytes are found in the Biomphalaria hemolymph: the granulocytes and the hyalinocytes. We studied the variation in the number (kinetics) of hemocytes for 24 h after exposing the parasite to genetically selected and non-selected strains of Biomphalaria tenagophila, susceptible or not to infection by Schistosoma mansoni. The differences were analyzed referred to the variations in the number of hemocytes in mollusks susceptible or not to infection by S. mansoni. The hemolymph of the selected and non-selected snails was collected, and hemocytes were counted using a Neubauer chamber at six designated periods: 0 h (control, non-exposed individuals), 2 h, 6 h, 12 h, 18 h and, 24 h after parasite exposure. Samples of hemolymph of five selected mollusks and five non-selected mollusks were separately used at each counting time. There was a significant variation in the number of hemocytes between the strains, which indicates that defense cells have different behaviors in resistant and susceptible mollusks.

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.

Direct Effects of Physcion, Chrysophanol, Emodin, and Pachybasin on Germination and Appressorium Formation of the Barley ( Hordeum vulgare L.) Powdery Mildew Fungus Blumeria graminis f. sp. hordei (DC.) Speer.

PubMed

Hildebrandt, Ulrich; Marsell, Alexander; Riederer, Markus

2018-04-04

Several anthraquinone derivatives are active components of fungicidal formulations particularly effective against powdery mildew fungi. The antimildew effect of compounds such as physcion and chrysophanol is largely attributed to host plant defense induction. However, so far a direct fungistatic/fungicidal effect of anthraquinone derivatives on powdery mildew fungi has not been unequivocally demonstrated. By applying a Formvar-based in vitro system we demonstrate a direct, dose-dependent effect of physcion, chrysophanol, emodin, and pachybasin on conidial germination and appressorium formation of Blumeria graminis f. sp. hordei (DC.) Speer, the causative agent of barley ( Hordeum vulgare L.) powdery mildew. Physcion was the most effective among the tested compounds. At higher doses, physcion mainly inhibited conidial germination. At lower rates, however, a distinct interference with appressorium formation became discernible. Physcion and others may act by modulating both the infection capacity of the powdery mildew pathogen and host plant defense. Our results suggest a specific arrangement of substituents at the anthraquinone backbone structure being crucial for the direct antimildew effect.

Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems

PubMed Central

Silas, Sukrit; Lucas-Elio, Patricia; Jackson, Simon A; Aroca-Crevillén, Alejandra; Hansen, Loren L; Fineran, Peter C

2017-01-01

CRISPR-Cas-mediated defense utilizes information stored as spacers in CRISPR arrays to defend against genetic invaders. We define the mode of target interference and role in antiviral defense for two CRISPR-Cas systems in Marinomonas mediterranea. One system (type I-F) targets DNA. A second system (type III-B) is broadly capable of acquiring spacers in either orientation from RNA and DNA, and exhibits transcription-dependent DNA interference. Examining resistance to phages isolated from Mediterranean seagrass meadows, we found that the type III-B machinery co-opts type I-F CRISPR-RNAs. Sequencing and infectivity assessments of related bacterial and phage strains suggests an ‘arms race’ in which phage escape from the type I-F system can be overcome through use of type I-F spacers by a horizontally-acquired type III-B system. We propose that the phage-host arms race can drive selection for horizontal uptake and maintenance of promiscuous type III interference modules that supplement existing host type I CRISPR-Cas systems. PMID:28826484

Macrophage migration inhibitory factor deficiency is associated with impaired killing of gram-negative bacteria by macrophages and increased susceptibility to Klebsiella pneumoniae sepsis.

PubMed

Roger, Thierry; Delaloye, Julie; Chanson, Anne-Laure; Giddey, Marlyse; Le Roy, Didier; Calandra, Thierry

2013-01-15

The cytokine macrophage migration inhibitory factor (MIF) is an important component of the early proinflammatory response of the innate immune system. However, the antimicrobial defense mechanisms mediated by MIF remain fairly mysterious. In the present study, we examined whether MIF controls bacterial uptake and clearance by professional phagocytes, using wild-type and MIF-deficient macrophages. MIF deficiency did not affect bacterial phagocytosis, but it strongly impaired the killing of gram-negative bacteria by macrophages and host defenses against gram-negative bacterial infection, as shown by increased mortality in a Klebsiella pneumonia model. Consistent with MIF's regulatory role of Toll-like 4 expression in macrophages, MIF-deficient cells stimulated with lipopolysaccharide or Escherichia coli exhibited reduced nuclear factor κB activity and tumor necrosis factor (TNF) production. Addition of recombinant MIF or TNF corrected the killing defect of MIF-deficient macrophages. Together, these data show that MIF is a key mediator of host responses against gram-negative bacteria, acting in part via a modulation of bacterial killing by macrophages.

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

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.

Characterization of a Viral Synergism in the Monocot Brachypodium distachyon Reveals Distinctly Altered Host Molecular Processes Associated with Disease1[C][W][OA

PubMed Central

Mandadi, Kranthi K.; Scholthof, Karen-Beth G.

2012-01-01

Panicum mosaic virus (PMV) and its satellite virus (SPMV) together infect several small grain crops, biofuel, and forage and turf grasses. Here, we establish the emerging monocot model Brachypodium (Brachypodium distachyon) as an alternate host to study PMV- and SPMV-host interactions and viral synergism. Infection of Brachypodium with PMV+SPMV induced chlorosis and necrosis of leaves, reduced seed set, caused stunting, and lowered biomass, more than PMV alone. Toward gaining a molecular understanding of PMV- and SPMV-affected host processes, we used a custom-designed microarray and analyzed global changes in gene expression of PMV- and PMV+SPMV-infected plants. PMV infection by itself modulated expression of putative genes functioning in carbon metabolism, photosynthesis, metabolite transport, protein modification, cell wall remodeling, and cell death. Many of these genes were additively altered in a coinfection with PMV+SPMV and correlated to the exacerbated symptoms of PMV+SPMV coinfected plants. PMV+SPMV coinfection also uniquely altered expression of certain genes, including transcription and splicing factors. Among the host defenses commonly affected in PMV and PMV+SPMV coinfections, expression of an antiviral RNA silencing component, SILENCING DEFECTIVE3, was suppressed. Several salicylic acid signaling components, such as pathogenesis-related genes and WRKY transcription factors, were up-regulated. By contrast, several genes in jasmonic acid and ethylene responses were down-regulated. Strikingly, numerous protein kinases, including several classes of receptor-like kinases, were misexpressed. Taken together, our results identified distinctly altered immune responses in monocot antiviral defenses and provide insights into monocot viral synergism. PMID:22961132

Host–Microbial Interactions in Idiopathic Pulmonary Fibrosis

PubMed Central

Willis-Owen, Saffron A. G.; Cox, Michael J.; James, Phillip; Cowman, Steven; Loebinger, Michael; Blanchard, Andrew; Edwards, Lindsay M.; Stock, Carmel; Daccord, Cécile; Renzoni, Elisabetta A.; Wells, Athol U.; Moffatt, Miriam F.; Cookson, William O. C.; Maher, Toby M.

2017-01-01

Rationale: Changes in the respiratory microbiome are associated with disease progression in idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome remains unknown. Objectives: To explore the host–microbial interactions in IPF. Methods: Sixty patients diagnosed with IPF were prospectively enrolled together with 20 matched control subjects. Subjects underwent bronchoalveolar lavage (BAL), and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For subjects with IPF, additional samples were taken at 1, 3, and 6 months and (if alive) 1 year. Gene expression profiles were generated using Affymetrix Human Gene 1.1 ST arrays. Measurements and Main Results: By network analysis of gene expression data, we identified two gene modules that strongly associated with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative polymerase chain reaction), and specific microbial operational taxonomic units, as well as with lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defense response include NLRC4, PGLYRP1, MMP9, and DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal overexpression in subjects experiencing disease progression, further strengthening the relationship of the transcripts with disease. Conclusions: Integrated analysis of the host transcriptome and microbial signatures demonstrated an apparent host response to the presence of an altered or more abundant microbiome. These responses remained elevated in longitudinal follow-up, suggesting that the bacterial communities of the lower airways may act as persistent stimuli for repetitive alveolar injury in IPF. PMID:28085486

Commensal-innate immune miscommunication in IBD pathogenesis.

PubMed

Cario, Elke

2012-01-01

Commensal microbiota plays a key role in the health and disease of the host. The innate immune system comprises an essential functional component of the intestinal mucosal barrier, maintaining hyporesponsiveness to omnipresent harmless commensals in the lumen, but rapidly recognizing and combating invading bacteria through diverse antimicrobial mechanisms. Interactions between commensals and innate immune cells are constant, multidimensional and entirely context-dependent. Environment, genetics and host defense differentially modulate commensal-innate immune effects and functions in the intestinal mucosa. In IBD, dysbiosis, mucus layer disruption, impairment in bacterial clearance, intestinal epithelial cell barrier dysfunction and/or immune cell deregulation may lead to commensal-innate immune miscommunication, which critically drives mucosal inflammation and associated cancer. Copyright © 2012 S. Karger AG, Basel.

Interferon Independent Non-Canonical STAT Activation and Virus Induced Inflammation

PubMed Central

Wu, Chunyan

2018-01-01

Interferons (IFNs) are a group of secreted proteins that play critical roles in antiviral immunity, antitumor activity, activation of cytotoxic T cells, and modulation of host immune responses. IFNs are cytokines, and bind receptors on cell surfaces to trigger signal transduction. The major signaling pathway activated by IFNs is the JAK/STAT (Janus kinase/signal transducer and activator of transcription) pathway, a complex pathway involved in both viral and host survival strategies. On the one hand, viruses have evolved strategies to escape from antiviral host defenses evoked by IFN-activated JAK/STAT signaling. On the other hand, viruses have also evolved to exploit the JAK/STAT pathway to evoke activation of certain STATs that somehow promote viral pathogenesis. In this review, recent progress in our understanding of the virus-induced IFN-independent STAT signaling and its potential roles in viral induced inflammation and pathogenesis are summarized in detail, and perspectives are provided. PMID:29662014

Accumulation of transcription factors and cell signaling-related proteins in the nucleus during citrus-Xanthomonas interaction.

PubMed

Rani, T Swaroopa; Durgeshwar, P; Podile, Appa Rao

2015-07-20

The nucleus is the maestro of the cell and is involved in the modulation of cell signaling during stress. We performed a comprehensive nuclear proteome analysis of Citrus sinensis during interaction with host (Xanthomonas citri pv. citri-Xcc) and non-host (Xanthomonas oryzae pv. oryzae-Xoo) pathogens. The nuclear proteome was obtained using a sequential method of organelle enrichment and determined by nano-LC-MS/MS analysis. A total of 243 proteins accumulated differentially during citrus-Xanthomonas interaction, belonging to 11 functional groups, with signaling and transcription-related proteins dominating. MADS-box transcription factors, DEAD-box RNA helicase and leucine aminopeptidase, mainly involved in jasmonic acid (JA) responses, were in high abundance during non-host interaction (Xoo). Signaling-related proteins like serine/threonine kinase, histones (H3.2, H2A), phosphoglycerate kinase, dynamin, actin and aldolase showed increased accumulation early during Xoo interaction. Our results suggest that there is a possible involvement of JA-triggered defense responses during non-host resistance, with early recognition of the non-host pathogen. Copyright © 2015. Published by Elsevier GmbH.

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...

The Host Defense Proteome of Human and Bovine Milk

PubMed Central

Hettinga, Kasper; van Valenberg, Hein; de Vries, Sacco; Boeren, Sjef; van Hooijdonk, Toon; van Arendonk, Johan; Vervoort, Jacques

2011-01-01

Milk is the single source of nutrients for the newborn mammal. The composition of milk of different mammals has been adapted during evolution of the species to fulfill the needs of the offspring. Milk not only provides nutrients, but it also serves as a medium for transfer of host defense components to the offspring. The host defense proteins in the milk of different mammalian species are expected to reveal signatures of evolution. The aim of this study is therefore to study the difference in the host defense proteome of human and bovine milk. We analyzed human and bovine milk using a shot-gun proteomics approach focusing on host defense-related proteins. In total, 268 proteins in human milk and 269 proteins in bovine milk were identified. Of these, 44 from human milk and 51 from bovine milk are related to the host defense system. Of these proteins, 33 were found in both species but with significantly different quantities. High concentrations of proteins involved in the mucosal immune system, immunoglobulin A, CD14, lactoferrin, and lysozyme, were present in human milk. The human newborn is known to be deficient for at least two of these proteins (immunoglobulin A and CD14). On the other hand, antimicrobial proteins (5 cathelicidins and lactoperoxidase) were abundant in bovine milk. The high concentration of lactoperoxidase is probably linked to the high amount of thiocyanate in the plant-based diet of cows. This first detailed analysis of host defense proteins in human and bovine milk is an important step in understanding the function of milk in the development of the immune system of these two mammals. PMID:21556375

Progranulin Plays a Central Role in Host Defense during Sepsis by Promoting Macrophage Recruitment.

PubMed

Song, Zhixin; Zhang, Xuemei; Zhang, Liping; Xu, Fang; Tao, Xintong; Zhang, Hua; Lin, Xue; Kang, Lihua; Xiang, Yu; Lai, Xaiofei; Zhang, Qun; Huang, Kun; Dai, Yubing; Yin, Yibing; Cao, Ju

2016-11-15

Progranulin, a widely expressed protein, has multiple physiological functions. The functional role of progranulin in the host response to sepsis remains unknown. To assess the role of progranulin in the host response to sepsis. Effects of progranulin on host response to sepsis were determined. Progranulin concentrations were significantly elevated in adult (n = 74) and pediatric (n = 26) patients with sepsis relative to corresponding healthy adult (n = 36) and pediatric (n = 17) control subjects, respectively. By using a low-lethality model of nonsevere sepsis, we observed that progranulin deficiency not only increased mortality but also decreased bacterial clearance during sepsis. The decreased host defense to sepsis in progranulin-deficient mice was associated with reduced macrophage recruitment, with correspondingly impaired chemokine CC receptor ligand 2 (CCL2) production in peritoneal lavages during the early phase of sepsis. Progranulin derived from hematopoietic cells contributed to host defense in sepsis. Therapeutic administration of recombinant progranulin not only rescued impaired host defense in progranulin-deficient mice after nonsevere sepsis but also protected wild-type mice against a high-lethality model of severe sepsis. Progranulin-mediated protection against sepsis was closely linked to improved peritoneal macrophage recruitment. In addition, CCL2 treatment of progranulin-deficient mice improved survival and decreased peritoneal bacterial loads during sepsis, at least in part through promotion of peritoneal macrophage recruitment. This proof-of-concept study supports a central role of progranulin-dependent macrophage recruitment in host defense to sepsis, opening new opportunities to host-directed therapeutic strategy that manipulate host immune response in the treatment of sepsis.

The Use of ATP-MgC1(2) in the Treatment of Injury and Shock.

DTIC Science & Technology

1979-12-01

not only have significance in terms of host defense against bacteremia but may also be associated with pulmonary changes which jeopardize the animals as...splenectomy may not only have deleterious effects in terms of host defense systems, but may also cause prolonged pulmonary changes which may jeopardize the...significance in terms of host defense against bacteremia but may also be associated with pulmonary changes which jeopardize the animal as well. B

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

The IκB family member Bcl-3 coordinates the pulmonary defense against Klebsiella pneumoniae infection.

PubMed

Pène, Frédéric; Paun, Andrea; Sønder, Søren Ulrik; Rikhi, Nimisha; Wang, Hongshan; Claudio, Estefania; Siebenlist, Ulrich

2011-02-15

Bcl-3 is an atypical member of the IκB family that has the potential to positively or negatively modulate nuclear NF-κB activity in a context-dependent manner. Bcl-3's biologic impact is complex and includes roles in tumorigenesis and diverse immune responses, including innate immunity. Bcl-3 may mediate LPS tolerance, suppressing cytokine production, but it also seems to contribute to defense against select systemic bacterial challenges. However, the potential role of Bcl-3 in organ-specific host defense against bacteria has not been addressed. In this study, we investigated the relevance of Bcl-3 in a lung challenge with the Gram-negative pathogen Klebsiella pneumoniae. In contrast to wild-type mice, Bcl-3-deficient mice exhibited significantly increased susceptibility toward K. pneumoniae pneumonia. The mutant mice showed increased lung damage marked by neutrophilic alveolar consolidation, and they failed to clear bacteria in lungs, which correlated with increased bacteremic dissemination. Loss of Bcl-3 incurred a dramatic cytokine imbalance in the lungs, which was characterized by higher levels of IL-10 and a near total absence of IFN-γ. Moreover, Bcl-3-deficient mice displayed increased lung production of the neutrophil-attracting chemokines CXCL-1 and CXCL-2. Alveolar macrophages and neutrophils are important to antibacterial lung defense. In vitro stimulation of Bcl-3-deficient alveolar macrophages with LPS or heat-killed K. pneumoniae recapitulated the increase in IL-10 production, and Bcl-3-deficient neutrophils were impaired in intracellular bacterial killing. These findings suggest that Bcl-3 is critically involved in lung defense against Gram-negative bacteria, modulating functions of several cells to facilitate efficient clearance of bacteria.

Social transmission of a host defense against cuckoo parasitism.

PubMed

Davies, Nicholas B; Welbergen, Justin A

2009-06-05

Coevolutionary arms races between brood parasites and hosts involve genetic adaptations and counter-adaptations. However, hosts sometimes acquire defenses too rapidly to reflect genetic change. Our field experiments show that observation of cuckoo (Cuculus canorus) mobbing by neighbors on adjacent territories induced reed warblers (Acrocephalus scirpaceus) to increase the mobbing of cuckoos but not of parrots (a harmless control) on their own territory. In contrast, observation of neighbors mobbing parrots had no effect on reed warblers' responses to either cuckoos or parrots. These results indicate that social learning provides a mechanism by which hosts rapidly increase their nest defense against brood parasites. Such enemy-specific social transmission enables hosts to track fine-scale spatiotemporal variation in parasitism and may influence the coevolutionary trajectories and population dynamics of brood parasites and hosts.

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.

The knottin-like Blufensin family regulates genes involved in nuclear import and the secretory pathway in barley-powdery mildew interactions

PubMed Central

Xu, Weihui; Meng, Yan; Surana, Priyanka; Fuerst, Greg; Nettleton, Dan; Wise, Roger P.

2015-01-01

Plants have evolved complex regulatory mechanisms to control a multi-layered defense response to microbial attack. Both temporal and spatial gene expression are tightly regulated in response to pathogen ingress, modulating both positive and negative control of defense. BLUFENSINs, small knottin-like peptides in barley, wheat, and rice, are highly induced by attack from fungal pathogens, in particular, the obligate biotrophic fungus, Blumeria graminis f. sp. hordei (Bgh), causal agent of barley powdery mildew. Previous research indicated that Blufensin1 (Bln1) functions as a negative regulator of basal defense mechanisms. In the current report, we show that BLN1 and BLN2 can both be secreted to the apoplast and Barley stripe mosaic virus (BSMV)-mediated overexpression of Bln2 increases susceptibility of barley to Bgh. Bimolecular fluorescence complementation (BiFC) assays signify that BLN1 and BLN2 can interact with each other, and with calmodulin. We then used BSMV-induced gene silencing to knock down Bln1, followed by Barley1 GeneChip transcriptome analysis, to identify additional host genes influenced by Bln1. Analysis of differential expression revealed a gene set enriched for those encoding proteins annotated to nuclear import and the secretory pathway, particularly Importin α1-b and Sec61 γ subunits. Further functional analysis of these two affected genes showed that when silenced, they also reduced susceptibility to Bgh. Taken together, we postulate that Bln1 is co-opted by Bgh to facilitate transport of disease-related host proteins or effectors, influencing the establishment of Bgh compatibility on its barley host. PMID:26089830

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

The LOV Protein of Xanthomonas citri subsp. citri Plays a Significant Role in the Counteraction of Plant Immune Responses during Citrus Canker

PubMed Central

Kraiselburd, Ivana; Daurelio, Lucas D.; Tondo, María Laura; Merelo, Paz; Cortadi, Adriana A.; Talón, Manuel; Tadeo, Francisco R.; Orellano, Elena G.

2013-01-01

Pathogens interaction with a host plant starts a set of immune responses that result in complex changes in gene expression and plant physiology. Light is an important modulator of plant defense response and recent studies have evidenced the novel influence of this environmental stimulus in the virulence of several bacterial pathogens. Xanthomonas citri subsp. citri is the bacterium responsible for citrus canker disease, which affects most citrus cultivars. The ability of this bacterium to colonize host plants is influenced by bacterial blue-light sensing through a LOV-domain protein and disease symptoms are considerably altered upon deletion of this protein. In this work we aimed to unravel the role of this photoreceptor during the bacterial counteraction of plant immune responses leading to citrus canker development. We performed a transcriptomic analysis in Citrus sinensis leaves inoculated with the wild type X. citri subsp. citri and with a mutant strain lacking the LOV protein by a cDNA microarray and evaluated the differentially regulated genes corresponding to specific biological processes. A down-regulation of photosynthesis-related genes (together with a corresponding decrease in photosynthesis rates) was observed upon bacterial infection, this effect being more pronounced in plants infected with the lov-mutant bacterial strain. Infection with this strain was also accompanied with the up-regulation of several secondary metabolism- and defense response-related genes. Moreover, we found that relevant plant physiological alterations triggered by pathogen attack such as cell wall fortification and tissue disruption were amplified during the lov-mutant strain infection. These results suggest the participation of the LOV-domain protein from X. citri subsp. citri in the bacterial counteraction of host plant defense response, contributing in this way to disease development. PMID:24260514

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].

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

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.

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

Sberro, Hila; Leavitt, Azita; Kiro, Ruth

Toxin-antitoxin (TA) modules, composed of a toxic protein and a counteracting antitoxin, play important roles in bacterial physiology. We examined the experimental insertion of 1.5 million genes from 388 microbial genomes into an Escherichia coli host using over 8.5 million random clones. This revealed hundreds of genes (toxins) that could only be cloned when the neighboring gene (antitoxin) was present on the same clone. Clustering of these genes revealed TA families widespread in bacterial genomes, some of which deviate from the classical characteristics previously described for such modules. Introduction of these genes into E. coli validated that the toxin toxicitymore » is mitigated by the antitoxin. Infection experiments with T7 phage showed that two of the new modules can provide resistance against phage. Moreover, our experiments revealed an 'anti-defense' protein in phage T7 that neutralizes phage resistance. Our results expose active fronts in the arms race between bacteria and phage.« less

MicroRNAs and non-coding RNAs in virus-infected cells

PubMed Central

Ouellet, Dominique L.; Provost, Patrick

2010-01-01

Within the past few years, microRNAs (miRNAs) and other non-coding RNAs (ncRNAs) have emerged as elements with critically high importance in post-transcriptional control of cellular and, more recently, viral processes. Endogenously produced by a component of the miRNA-guided RNA silencing machinery known as Dicer, miRNAs are known to control messenger RNA (mRNA) translation through recognition of specific binding sites usually located in their 3′ untranslated region. Recent evidences indicate that the host miRNA pathway may represent an adapted antiviral defense mechanism that can act either by direct miRNA-mediated modulation of viral gene expression or through recognition and inactivation of structured viral RNA species by the protein components of the RNA silencing machinery, such as Dicer. This latter process, however, is a double-edge sword, as it may yield viral miRNAs exerting gene regulatory properties on both host and viral mRNAs. Our knowledge of the interaction between viruses and host RNA silencing machineries, and how this influences the course of infection, is becoming increasingly complex. This review article aims to summarize our current knowledge about viral miRNAs/ncRNAs and their targets, as well as cellular miRNAs that are modulated by viruses upon infection. PMID:20217543

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.

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.

Natural History of Innate Host Defense Peptides.

PubMed

Linde, A; Wachter, B; Höner, O P; Dib, L; Ross, C; Tamayo, A R; Blecha, F; Melgarejo, T

2009-12-01

Host defense peptides act on the forefront of innate immunity, thus playing a central role in the survival of animals and plants. Despite vast morphological changes in species through evolutionary history, all animals examined to date share common features in their innate immune defense strategies, hereunder expression of host defense peptides (HDPs). Most studies on HDPs have focused on humans, domestic and laboratory animals. More than a thousand different sequences have been identified, yet data on HDPs in wild-living animals are sparse. The biological functions of HDPs include broad-spectrum antimicrobial activity and immunomodulation. Natural selection and coevolutionary host-pathogen arms race theory suggest that the extent and specificity of the microbial load influences the spectrum and potency of HDPs in different species. Individuals of extant species-that have lived for an extended period in evolutionary history amid populations with intact processes of natural selection-likely possess the most powerful and well-adapted "natural antibiotics". Research on the evolutionary history of the innate defense system and the host in context of the consequences of challenges as well as the efficacy of the innate immune system under natural conditions is therefore of immediate interest. This review focuses on evolutionary aspects of immunophysiology, with emphasis on innate effector molecules. Studies on host defense in wild-living animals may significantly enhance our understanding of inborn immune mechanisms, and help identify molecules that may assist us to cope better with the increasing microbial challenges that likely follow from the continuous amplification of biodiversity levels on Earth.

Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function

PubMed Central

Sokolovska, Anna; Becker, Christine E.; Eddie Ip, WK; Rathinam, Vijay A.K.; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Vanaja, Sivapriya K.; Moore, Kathryn J.; Fitzgerald, Katherine A.; Lacy-Hulbert, Adam; Stuart, Lynda M.

2013-01-01

Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates a number of functions of these organelles that allow them to participate in processes essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3-inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3-inflammasome and caspase-1 in host defense. PMID:23644505

Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes.

PubMed

Lee, Kyung-Ah; Kim, Boram; Bhin, Jinhyuk; Kim, Do Hun; You, Hyejin; Kim, Eun-Kyoung; Kim, Sung-Hee; Ryu, Ji-Hwan; Hwang, Daehee; Lee, Won-Jae

2015-02-11

Genetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLCβ/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of Cad99C into enterocytes, demonstrating the important role for Hh signaling in host resistance to enteric infection. Copyright © 2015 Elsevier Inc. All rights reserved.

An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection.

PubMed

Akram, K M; Moyo, N A; Leeming, G H; Bingle, L; Jasim, S; Hussain, S; Schorlemmer, A; Kipar, A; Digard, P; Tripp, R A; Shohet, R V; Bingle, C D; Stewart, J P

2018-01-01

The airway epithelium secretes proteins that function in innate defense against infection. Bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism, we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties. We show that BPIFA1 has a significant role in mucosal defense against IAV infection. BPIFA1 secretion was highly modulated after IAV infection. Mice deficient in BPIFA1 lost more weight after infection, supported a higher viral load and virus reached the peripheral lung earlier, indicative of a defect in the control of infection. Further analysis using mTEC cultures showed that BPIFA1-deficient cells bound more virus particles, displayed increased nuclear import of IAV ribonucleoprotein complexes, and supported higher levels of viral replication. Our results identify a critical role of BPIFA1 in the initial phase of infection by inhibiting the binding and entry of IAV into airway epithelial cells.

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

Endophytic Epichloë species and their grass hosts: from evolution to applications.

PubMed

Saikkonen, Kari; Young, Carolyn A; Helander, Marjo; Schardl, Christopher L

2016-04-01

The closely linked fitness of the Epichloë symbiont and the host grass is presumed to align the coevolution of the species towards specialization and mutually beneficial cooperation. Ecological observations demonstrating that Epichloë-grass symbioses can modulate grassland ecosystems via both above- and belowground ecosystem processes support this. In many cases the detected ecological importance of Epichloë species is directly or indirectly linked to defensive mutualism attributable to alkaloids of fungal-origin. Now, modern genetic and molecular techniques enable the precise studies on evolutionary origin of endophytic Epichloë species, their coevolution with host grasses and identification the genetic variation that explains phenotypic diversity in ecologically relevant characteristics of Epichloë-grass associations. Here we briefly review the most recent findings in these areas of research using the present knowledge of the genetic variation that explains the biosynthetic pathways driving the diversity of alkaloids produced by the endophyte. These findings underscore the importance of genetic interplay between the fungus and the host in shaping their coevolution and ecological role in both natural grass ecosystems, and in the agricultural arena.

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

ERIC Educational Resources Information Center

Suresh, Rahul; Mosser, David M.

2013-01-01

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

Evolution of African swine fever virus genes related to evasion of host immune response.

PubMed

Frączyk, Magdalena; Woźniakowski, Grzegorz; Kowalczyk, Andrzej; Bocian, Łukasz; Kozak, Edyta; Niemczuk, Krzysztof; Pejsak, Zygmunt

2016-09-25

African swine fever (ASF) is a notifiable and one of the most complex and devastating infectious disease of pigs, wild boars and other representatives of Suidae family. African swine fever virus (ASFV) developed various molecular mechanisms to evade host immune response including alteration of interferon production by multigene family protein (MGF505-2R), inhibition of NF-κB and nuclear activating factor in T-cells by the A238L protein, or modulation of host defense by CD2v lectin-like protein encoded by EP402R and EP153R genes. The current situation concerning ASF in Poland seems to be stable in comparison to other eastern European countries but up-to-date in total 106 ASF cases in wild boar and 5 outbreaks in pigs were identified. The presented study aimed to reveal and summarize the genetic variability of genes related to inhibition or modulation of infected host response among 67 field ASF isolates collected from wild boar and pigs. The nucleotide sequences derived from the analysed A238L and EP153R regions showed 100% identity. However, minor but remarkable genetic diversity was found within EP402R and MGF505-2R genes suggesting slow molecular evolution of circulating ASFV isolates and the important role of this gene in modulation of interferon I production and hemadsorption phenomenon. The obtained nucleotide sequences of Polish ASFV isolates were closely related to Georgia 2007/1 and Odintsovo 02/14 isolates suggesting their common Caucasian origin. In the case of EP402R and partially in MGF505-2R gene the identified genetic variability was related to spatio-temporal occurrence of particular cases and outbreaks what may facilitate evolution tracing of ASFV isolates. This is the first report indicating identification of genetic variability within the genes related to evasion of host immune system which may be used to trace the direction of ASFV isolates molecular evolution. Copyright © 2016 Elsevier B.V. All rights reserved.

Experimental demonstration of a parasite-induced immune response in wild birds: Darwin's finches and introduced nest flies.

PubMed

Koop, Jennifer A H; Owen, Jeb P; Knutie, Sarah A; Aguilar, Maria A; Clayton, Dale H

2013-08-01

Ecological immunology aims to explain variation among hosts in the strength and efficacy of immunological defenses. However, a shortcoming has been the failure to link host immune responses to actual parasites under natural conditions. Here, we present one of the first experimental demonstrations of a parasite-induced immune response in a wild bird population. The recently introduced ectoparasitic nest fly Philornis downsi severely impacts the fitness of Darwin's finches and other land birds in the Galápagos Islands. An earlier study showed that female medium ground finches (Geospiza fortis) had P. downsi-binding antibodies correlating with presumed variation in fly exposure over time. In the current study, we experimentally manipulated fly abundance to test whether the fly does, in fact, cause changes in antibody levels. We manipulated P. downsi abundance in nests and quantified P. downsi-binding antibody levels of medium ground finch mothers, fathers, and nestlings. We also quantified host behaviors, such as preening, which can integrate with antibody-mediated defenses against ectoparasites. Philornis downsi-binding antibody levels were significantly higher among mothers at parasitized nests, compared to mothers at (fumigated) nonparasitized nests. Mothers with higher antibody levels tended to have fewer parasites in their nests, suggesting that antibodies play a role in defense against parasites. Mothers showed no behavioral changes that would enhance the effectiveness of the immune response. Neither adult males, nor nestlings, had P. downsi-induced immunological or behavioral responses that would enhance defense against flies. None of the parasitized nests fledged any offspring, despite the immune response by mothers. Thus, this study shows that, while the immune response of mothers appeared to be defensive, it was not sufficient to rescue current reproductive fitness. This study further shows the importance of testing the fitness consequences of immune defenses, rather than assuming that such responses increase host fitness. Host immune responses can protect against the negative fitness consequences of parasitism; however, the strength and effectiveness of these responses vary among hosts. Strong host immune responses are often assumed to correlate with greater host fitness. This study investigates the relationship between host immune response, parasite load, and host fitness using Darwin's finches and an invasive nest parasite. We found that while the immune response of mothers appeared defensive, it did not rescue current reproductive fitness.

Salt, chloride, bleach, and innate host defense

PubMed Central

Wang, Guoshun; Nauseef, William M.

2015-01-01

Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. PMID:26048979

Salt, chloride, bleach, and innate host defense.

PubMed

Wang, Guoshun; Nauseef, William M

2015-08-01

Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. © Society for Leukocyte Biology.

Induced plant defenses, host–pathogen interactions, and forest insect outbreaks

PubMed Central

Elderd, Bret D.; Rehill, Brian J.; Haynes, Kyle J.; Dwyer, Greg

2013-01-01

Cyclic outbreaks of defoliating insects devastate forests, but their causes are poorly understood. Outbreak cycles are often assumed to be driven by density-dependent mortality due to natural enemies, because pathogens and predators cause high mortality and because natural-enemy models reproduce fluctuations in defoliation data. The role of induced defenses is in contrast often dismissed, because toxic effects of defenses are often weak and because induced-defense models explain defoliation data no better than natural-enemy models. Natural-enemy models, however, fail to explain gypsy moth outbreaks in North America, in which outbreaks in forests with a higher percentage of oaks have alternated between severe and mild, whereas outbreaks in forests with a lower percentage of oaks have been uniformly moderate. Here we show that this pattern can be explained by an interaction between induced defenses and a natural enemy. We experimentally induced hydrolyzable-tannin defenses in red oak, to show that induction reduces variability in a gypsy moth’s risk of baculovirus infection. Because this effect can modulate outbreak severity and because oaks are the only genus of gypsy moth host tree that can be induced, we extended a natural-enemy model to allow for spatial variability in inducibility. Our model shows alternating outbreaks in forests with a high frequency of oaks, and uniform outbreaks in forests with a low frequency of oaks, matching the data. The complexity of this effect suggests that detecting effects of induced defenses on defoliator cycles requires a combination of experiments and models. PMID:23966566

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

PubMed

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

2016-01-01

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

Factor H: A Complement Regulator in Health and Disease, and a Mediator of Cellular Interactions

PubMed Central

Kopp, Anne; Hebecker, Mario; Svobodová, Eliška; Józsi, Mihály

2012-01-01

Complement is an essential part of innate immunity as it participates in host defense against infections, disposal of cellular debris and apoptotic cells, inflammatory processes and modulation of adaptive immune responses. Several soluble and membrane-bound regulators protect the host from the potentially deleterious effects of uncontrolled and misdirected complement activation. Factor H is a major soluble regulator of the alternative complement pathway, but it can also bind to host cells and tissues, protecting them from complement attack. Interactions of factor H with various endogenous ligands, such as pentraxins, extracellular matrix proteins and DNA are important in limiting local complement-mediated inflammation. Impaired regulatory as well as ligand and cell recognition functions of factor H, caused by mutations or autoantibodies, are associated with the kidney diseases: atypical hemolytic uremic syndrome and dense deposit disease and the eye disorder: age-related macular degeneration. In addition, factor H binds to receptors on host cells and is involved in adhesion, phagocytosis and modulation of cell activation. In this review we discuss current concepts on the physiological and pathophysiological roles of factor H in light of new data and recent developments in our understanding of the versatile roles of factor H as an inhibitor of complement activation and inflammation, as well as a mediator of cellular interactions. A detailed knowledge of the functions of factor H in health and disease is expected to unravel novel therapeutic intervention possibilities and to facilitate the development or improvement of therapies. PMID:24970127

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.

Burkholderia cenocepacia Lipopolysaccharide Modification and Flagellin Glycosylation Affect Virulence but Not Innate Immune Recognition in Plants

PubMed Central

Khodai-Kalaki, Maryam; Andrade, Angel; Fathy Mohamed, Yasmine

2015-01-01

ABSTRACT Burkholderia cenocepacia causes opportunistic infections in plants, insects, animals, and humans, suggesting that “virulence” depends on the host and its innate susceptibility to infection. We hypothesized that modifications in key bacterial molecules recognized by the innate immune system modulate host responses to B. cenocepacia. Indeed, modification of lipopolysaccharide (LPS) with 4-amino-4-deoxy-l-arabinose and flagellin glycosylation attenuates B. cenocepacia infection in Arabidopsis thaliana and Galleria mellonella insect larvae. However, B. cenocepacia LPS and flagellin triggered rapid bursts of nitric oxide and reactive oxygen species in A. thaliana leading to activation of the PR-1 defense gene. These responses were drastically reduced in plants with fls2 (flagellin FLS2 host receptor kinase), Atnoa1 (nitric oxide-associated protein 1), and dnd1-1 (reduced production of nitric oxide) null mutations. Together, our results indicate that LPS modification and flagellin glycosylation do not affect recognition by plant receptors but are required for bacteria to establish overt infection. PMID:26045541

Vibrio vulnificus quorum-sensing molecule cyclo(Phe-Pro) inhibits RIG-I-mediated antiviral innate immunity.

PubMed

Lee, Wooseong; Lee, Seung-Hoon; Kim, Minwoo; Moon, Jae-Su; Kim, Geon-Woo; Jung, Hae-Gwang; Kim, In Hwang; Oh, Ji Eun; Jung, Hi Eun; Lee, Heung Kyu; Ku, Keun Bon; Ahn, Dae-Gyun; Kim, Seong-Jun; Kim, Kun-Soo; Oh, Jong-Won

2018-04-23

The recognition of pathogen-derived ligands by pattern recognition receptors activates the innate immune response, but the potential interaction of quorum-sensing (QS) signaling molecules with host anti-viral defenses remains largely unknown. Here we show that the Vibrio vulnificus QS molecule cyclo(Phe-Pro) (cFP) inhibits interferon (IFN)-β production by interfering with retinoic-acid-inducible gene-I (RIG-I) activation. Binding of cFP to the RIG-I 2CARD domain induces a conformational change in RIG-I, preventing the TRIM25-mediated ubiquitination to abrogate IFN production. cFP enhances susceptibility to hepatitis C virus (HCV), as well as Sendai and influenza viruses, each known to be sensed by RIG-I but did not affect the melanoma-differentiation-associated gene 5 (MDA5)-recognition of norovirus. Our results reveal an inter-kingdom network between bacteria, viruses and host that dysregulates host innate responses via a microbial quorum-sensing molecule modulating the response to viral infection.

Secondary metabolites in fungus-plant interactions

PubMed Central

Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

2015-01-01

Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

Helminths: Immunoregulation and Inflammatory Diseases—Which Side Are Trichinella spp. and Toxocara spp. on?

PubMed Central

Aranzamendi, Carmen; Sofronic-Milosavljevic, Ljiljana; Pinelli, Elena

2013-01-01

Macropathogens, such as multicellular helminths, are considered masters of immunoregulation due to their ability to escape host defense and establish chronic infections. Molecular crosstalk between the host and the parasite starts immediately after their encounter, which influences the course and development of both the innate and adaptive arms of the immune response. Helminths can modulate dendritic cells (DCs) function and induce immunosuppression which is mediated by a regulatory network that includes regulatory T (Treg) cells, regulatory B (Breg) cells, and alternatively activated macrophages (AAMs). In this way, helminths suppress and control both parasite-specific and unrelated immunopathology in the host such as Th1-mediated autoimmune and Th2-mediated allergic diseases. However, certain helminths favour the development or exacerbation of allergic responses. In this paper, the cell types that play an essential role in helminth-induced immunoregulation, the consequences for inflammatory diseases, and the contrasting effects of Toxocara and Trichinella infection on allergic manifestations are discussed. PMID:23365718

Regulation of DUOX by the Galphaq-phospholipase Cbeta-Ca2+ pathway in Drosophila gut immunity.

PubMed

Ha, Eun-Mi; Lee, Kyung-Ah; Park, Seon Hwa; Kim, Sung-Hee; Nam, Hyuck-Jin; Lee, Hyo-Young; Kang, Dongmin; Lee, Won-Jae

2009-03-01

All metazoan guts are in constant contact with diverse food-borne microorganisms. The signaling mechanisms by which the host regulates gut-microbe interactions, however, are not yet clear. Here, we show that phospholipase C-beta (PLCbeta) signaling modulates dual oxidase (DUOX) activity to produce microbicidal reactive oxygen species (ROS) essential for normal host survival. Gut-microbe contact rapidly activates PLCbeta through Galphaq, which in turn mobilizes intracellular Ca(2+) through inositol 1,4,5-trisphosphate generation for DUOX-dependent ROS production. PLCbeta mutant flies had a short life span due to the uncontrolled propagation of an essential nutritional microbe, Saccharomyces cerevisiae, in the gut. Gut-specific reintroduction of the PLCbeta restored efficient DUOX-dependent microbe-eliminating capacity and normal host survival. These results demonstrate that the Galphaq-PLCbeta-Ca(2+)-DUOX-ROS signaling pathway acts as a bona fide first line of defense that enables gut epithelia to dynamically control yeast during the Drosophila life cycle.

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.

Thrombospondin-1 protects against pathogen-induced lung injury by limiting extracellular matrix proteolysis

PubMed Central

Qu, Yanyan; Olonisakin, Tolani; Bain, William; Zupetic, Jill; Brown, Rebecca; Hulver, Mei; Xiong, Zeyu; Shanks, Robert M.Q.; Bomberger, Jennifer M.; Cooper, Vaughn S.; Zegans, Michael E.; Han, Jongyoon; Pilewski, Joseph; Ray, Anuradha; Ray, Prabir; Lee, Janet S.

2018-01-01

Acute lung injury is characterized by excessive extracellular matrix proteolysis and neutrophilic inflammation. A major risk factor for lung injury is bacterial pneumonia. However, host factors that protect against pathogen-induced and host-sustained proteolytic injury following infection are poorly understood. Pseudomonas aeruginosa (PA) is a major cause of nosocomial pneumonia and secretes proteases to amplify tissue injury. We show that thrombospondin-1 (TSP-1), a matricellular glycoprotein released during inflammation, dose-dependently inhibits PA metalloendoprotease LasB, a virulence factor. TSP-1–deficient (Thbs1–/–) mice show reduced survival, impaired host defense, and increased lung permeability with exaggerated neutrophil activation following acute intrapulmonary PA infection. Administration of TSP-1 from platelets corrects the impaired host defense and aberrant injury in Thbs1–/– mice. Although TSP-1 is cleaved into 2 fragments by PA, TSP-1 substantially inhibits Pseudomonas elastolytic activity. Administration of LasB inhibitor, genetic disabling of the PA type II secretion system, or functional deletion of LasB improves host defense and neutrophilic inflammation in mice. Moreover, TSP-1 provides an additional line of defense by directly subduing host-derived proteolysis, with dose-dependent inhibition of neutrophil elastase from airway neutrophils of mechanically ventilated critically ill patients. Thus, a host matricellular protein provides dual levels of protection against pathogen-initiated and host-sustained proteolytic injury following microbial trigger. PMID:29415890

DARPA Orbital Express program: effecting a revolution in space-based systems

NASA Astrophysics Data System (ADS)

Whelan, David A.; Adler, E. A.; Wilson, Samuel B., III; Roesler, Gordon M., Jr.

2000-11-01

A primary goal of the Defense Advanced Research Projects Agency is to develop innovative, high-risk technologies with the potential of a revolutionary impact on missions of the Department of Defense. DARPA is developing a space experiment to prove the feasibility of autonomous on- orbit servicing of spacecraft. The Orbital Express program will demonstrate autonomous on-orbit refueling, as well as autonomous delivery of a small payload representing an avionics upgrade package. The maneuverability provided to spacecraft from a ready refueling infrastructure will enable radical new capabilities for the military, civil and commercial spacecraft. Module replacement has the potential to extend bus lifetimes, and to upgrade the performance of key subsystems (e.g. processors) at the pace of technology development. The Orbital Express technology development effort will include the necessary autonomy for a viable servicing infrastructure; a universal interface for docking, refueling and module transfers; and a spacecraft bus design compatible with this servicing concept. The servicer spacecraft of the future may be able to act as a host platform for microsatellites, extending their capabilities while reducing risk. An infrastructure based on Orbital Express also benefits from, and stimulates the development of, lower-cost launch strategies.

Toward Understanding Phage:Host Interactions in the Rumen; Complete Genome Sequences of Lytic Phages Infecting Rumen Bacteria

PubMed Central

Gilbert, Rosalind A.; Kelly, William J.; Altermann, Eric; Leahy, Sinead C.; Minchin, Catherine; Ouwerkerk, Diane; Klieve, Athol V.

2017-01-01

The rumen is known to harbor dense populations of bacteriophages (phages) predicted to be capable of infecting a diverse range of rumen bacteria. While bacterial genome sequencing projects are revealing the presence of phages which can integrate their DNA into the genome of their host to form stable, lysogenic associations, little is known of the genetics of phages which utilize lytic replication. These phages infect and replicate within the host, culminating in host lysis, and the release of progeny phage particles. While lytic phages for rumen bacteria have been previously isolated, their genomes have remained largely uncharacterized. Here we report the first complete genome sequences of lytic phage isolates specifically infecting three genera of rumen bacteria: Bacteroides, Ruminococcus, and Streptococcus. All phages were classified within the viral order Caudovirales and include two phage morphotypes, representative of the Siphoviridae and Podoviridae families. The phage genomes displayed modular organization and conserved viral genes were identified which enabled further classification and determination of closest phage relatives. Co-examination of bacterial host genomes led to the identification of several genes responsible for modulating phage:host interactions, including CRISPR/Cas elements and restriction-modification phage defense systems. These findings provide new genetic information and insights into how lytic phages may interact with bacteria of the rumen microbiome. PMID:29259581

An experimental test of host’s life history traits modulation in response to cuckoo parasitism risk

PubMed Central

Parejo, Deseada; Martínez, Juan Gabriel; Sánchez-Tójar, Alfredo; Precioso, Marta; Molina-Morales, Mercedes; Avilés, Jesús M.

2017-01-01

Hosts can counteract parasites through defences based on resistance and/or tolerance. The mechanistic basis of tolerance, which involve defensive mechanisms minimizing parasite damage after a successful parasitic attack, remains poorly explored in the study of cuckoo-host interactions. Here, we experimentally explore the possibility that the risk of great spotted cuckoo Clamator glandarius parasitism may induce tolerance defences in magpie Pica pica hosts through plasticity in life-history traits. We predict that magpies exposed to auditory cues indicating high parasitism risk will more likely exhibit resistance and/or modify their life-history traits to minimize parasitism costs (i.e. tolerance) compared to magpies under low parasitism risk. We found that manipulating the perceived parasitism risk did not affect host resistance (i.e. rejection of parasitic eggs) nor host life-history traits. Unexpectedly, host’s egg volume increased over the season in nests exposed to auditory cues of control non-harmful hoopoes Upupa epops. Our results do not provide support for inducible defences (either based on resistance or tolerance) in response to risk of parasitism in magpie hosts. Even so, we encourage studying plastic expression of breeding strategies in response to risk of cuckoo parasitism to achieve a better understanding of the mechanistic basis of tolerance defences. PMID:28658287

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.

First evidence for slave rebellion: enslaved ant workers systematically kill the brood of their social parasite protomognathus americanus.

PubMed

Achenbach, Alexandra; Foitzik, Susanne

2009-04-01

During the process of coevolution, social parasites have evolved sophisticated strategies to exploit the brood care behavior of their social hosts. Slave-making ant queens invade host colonies and kill or eject all adult host ants. Host workers, which eclose from the remaining brood, are tricked into caring for the parasite brood. Due to their high prevalence and frequent raids, following which stolen host broods are similarly enslaved, slave-making ants exert substantial selection upon their hosts, leading to the evolution of antiparasite adaptations. However, all host defenses shown to date are active before host workers are parasitized, whereas selection was thought to be unable to act on traits of already enslaved hosts. Yet, here we demonstrate the rebellion of enslaved Temnothorax workers, which kill two-thirds of the female pupae of the slave-making ant Protomognathus americanus. Thereby, slaves decrease the long-term parasite impact on surrounding related host colonies. This novel antiparasite strategy of enslaved workers constitutes a new level in the coevolutionary battle after host colony defense has failed. Our discovery is analogous to recent findings in hosts of avian brood parasites where perfect mimicry of parasite eggs leads to the evolution of chick recognition as a second line of defense.

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.

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.

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

The role of TGF-β signaling and apoptosis in innate and adaptive immunity in zebrafish: a systems biology approach.

PubMed

Lin, Che; Lin, Chin-Nan; Wang, Yu-Chao; Liu, Fang-Yu; Chuang, Yung-Jen; Lan, Chung-Yu; Hsieh, Wen-Ping; Chen, Bor-Sen

2014-10-24

The immune system is a key biological system present in vertebrates. Exposure to pathogens elicits various defensive immune mechanisms that protect the host from potential threats and harmful substances derived from pathogens such as parasites, bacteria, and viruses. The complex immune system of humans and many other vertebrates can be divided into two major categories: the innate and the adaptive immune systems. At present, analysis of the complex interactions between the two subsystems that regulate host defense and inflammatory responses remains challenging. Based on time-course microarray data following primary and secondary infection of zebrafish by Candida albicans, we constructed two intracellular protein-protein interaction (PPI) networks for primary and secondary responses of the host. 57 proteins and 341 PPIs were identified for primary infection while 90 proteins and 385 PPIs were identified for secondary infection. There were 20 proteins in common while 37 and 70 proteins specific to primary and secondary infection. By inspecting the hub proteins of each network and comparing significant changes in the number of linkages between the two PPI networks, we identified TGF-β signaling and apoptosis as two of the main functional modules involved in primary and secondary infection. Our initial in silico analyses pave the way for further investigation into the interesting roles played by the TGF-β signaling pathway and apoptosis in innate and adaptive immunity in zebrafish. Such insights could lead to therapeutic advances and improved drug design in the continual battle against infectious diseases.

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.

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.

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.

Chemically modified tetracyclines an emerging host modulator in chronic periodontitis patients: A randomized, double-blind, placebo-controlled, clinical trial.

PubMed

Alyousef, Abdullah A; Divakar, Darshan Devang; Muzaheed

2017-09-01

Although periodontal diseases are caused by some of the specific pathogens, most of the tissue damage is caused by the host reaction to disease and not actually by the infections. Therefore, host modulatory therapy (HMT) has advanced benefit for the treatment of periodontitis, which works basically by reducing tissue destruction and regeneration in periodontium by altering the critical aspects of host response regulation and up regulating defensive regenerative responses. The present study was conducted with the goal to test an innovative therapeutic option using chemically modified tetracycline in patients affected with generalized, moderate and severe chronic periodontitis. We assumed that CMT might have the potential to provoke an assessable clinical result and pharmacologically impede the level inflammatory flow. CMT (incyclinide) treated group had significantly higher CAL (clinical attachment) values than Placebo Control suggesting an improved CAL in CMT treatment. Host modulation therapy width incyclinide can be as an adjunct to conventional nonsurgical therapies without antimicrobial resistance. Progress was noticed in the clinical parameters but not the serum CRP level in our study establishing the role of CMTs in controlling chronic periodontitis. Also CMT treatment indicates its role in anti-inflammatory process as it inhibited IL-12 and TNF alpha but IL-10 level was not affected. However, more randomized placebo-controlled clinical trials with large sample size are required in order to authenticate the usage of CMTs in chronic periodontitis treatment. Based on this understanding, exploration of the novel, low-cost synthetic inhibitors that can be used as potential therapeutic agents, has been tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

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.

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...

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...

32 CFR 344.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false Definitions. 344.3 Section 344.3 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) ORGANIZATIONAL... employees), contractor staff, and host-nation support personnel. ...

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.

A novel approach for emerging and antibiotic resistant infections: Innate Defense Regulators as an agnostic therapy

PubMed Central

North, John R.; Takenaka, Shunsuke; Rozek, Annett; Kielczewska, Agnieszka; Opal, Steven; Morici, Lisa A.; Finlay, B. Brett; Schaber, Christopher J.; Straube, Richard; Donini, Oreola

2016-01-01

Innate Defense Regulators (IDRs) are short synthetic peptides that target the host innate immune system via an intracellular adaptor protein which functions at key signaling nodes. In this work, further details of the mechanism of action of IDRs have been discovered. The studies reported here show that the lead clinical IDR, SGX94, has broad-spectrum activity against Gram-negative and Gram-positive bacterial infections caused by intracellular or extracellular bacteria and also complements the actions of standard of care antibiotics. Based on in vivo and primary cell culture studies, this activity is shown to result from the primary action of SGX94 on tissue-resident cells and subsequent secondary signaling to activate myeloid-derived cells, resulting in enhanced bacterial clearance and increased survival. Data from non-clinical and clinical studies also show that SGX94 treatment modulates pro-inflammatory and anti-inflammatory cytokine levels, thereby mitigating the deleterious inflammatory consequences of innate immune activation. Since they act through host pathways to provide both broad-spectrum anti-infective capability as well as control of inflammation, IDRs are unlikely to be impacted by resistance mechanisms and offer potential clinical advantages in the fight against emerging and antibiotic resistant bacterial infections. PMID:27015977

Contrasting diets reveal metabolic plasticity in the tree-killing beetle, Anoplophora glabripennis (Cerambycidae: Lamiinae)

NASA Astrophysics Data System (ADS)

Mason, Charles J.; Scully, Erin D.; Geib, Scott M.; Hoover, Kelli

2016-09-01

Wood-feeding insects encounter challenging diets containing low protein quantities, recalcitrant carbohydrate sources, and plant defensive compounds. The Asian longhorned beetle (Anoplophora glabripennis) is a wood-feeding insect that attacks and kills a diversity of hardwood tree species. We compared gene expression of midguts collected from larvae feeding in a preferred tree, sugar maple, to those consuming a nutrient-rich artificial diet, to identify genes putatively involved in host plant utilization. Anoplophora glabripennis larvae exhibited differential expression of ~3600 genes in response to different diets. Genes with predicted capacity for plant and microbial carbohydrate usage, detoxification, nutrient recycling, and immune-related genes relevant for facilitating interactions with microbial symbionts were upregulated in wood-feeding larvae compared to larvae feeding in artificial diet. Upregulation of genes involved in protein degradation and synthesis was also observed, suggesting that proteins incur more rapid turnover in insects consuming wood. Additionally, wood-feeding individuals exhibited elevated expression of several mitochondrial cytochrome C oxidase genes, suggesting increased aerobic respiration compared to diet-fed larvae. These results indicate that A. glabripennis modulates digestive and basal gene expression when larvae are feeding in a nutrient-poor, yet suitable host plant compared to a tractable and nutrient-rich diet that is free of plant defensive compounds.

A novel approach for emerging and antibiotic resistant infections: Innate defense regulators as an agnostic therapy.

PubMed

North, John R; Takenaka, Shunsuke; Rozek, Annett; Kielczewska, Agnieszka; Opal, Steven; Morici, Lisa A; Finlay, B Brett; Schaber, Christopher J; Straube, Richard; Donini, Oreola

2016-05-20

Innate Defense Regulators (IDRs) are short synthetic peptides that target the host innate immune system via an intracellular adaptor protein which functions at key signaling nodes. In this work, further details of the mechanism of action of IDRs have been discovered. The studies reported here show that the lead clinical IDR, SGX94, has broad-spectrum activity against Gram-negative and Gram-positive bacterial infections caused by intracellular or extracellular bacteria and also complements the actions of standard of care antibiotics. Based on in vivo and primary cell culture studies, this activity is shown to result from the primary action of SGX94 on tissue-resident cells and subsequent secondary signaling to activate myeloid-derived cells, resulting in enhanced bacterial clearance and increased survival. Data from non-clinical and clinical studies also show that SGX94 treatment modulates pro-inflammatory and anti-inflammatory cytokine levels, thereby mitigating the deleterious inflammatory consequences of innate immune activation. Since they act through host pathways to provide both broad-spectrum anti-infective capability as well as control of inflammation, IDRs are unlikely to be impacted by resistance mechanisms and offer potential clinical advantages in the fight against emerging and antibiotic resistant bacterial infections. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1

PubMed Central

Yu, Xiaoliang; Li, Yun; Chen, Qin; Su, Chenhe; Zhang, Zili; Yang, Chengkui; Hu, Zhilin; Hou, Jue; Zhou, Jinying; Gong, Ling; Jiang, Xuejun

2015-01-01

ABSTRACT Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. IMPORTANCE This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV. PMID:26559832

Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1.

PubMed

Yu, Xiaoliang; Li, Yun; Chen, Qin; Su, Chenhe; Zhang, Zili; Yang, Chengkui; Hu, Zhilin; Hou, Jue; Zhou, Jinying; Gong, Ling; Jiang, Xuejun; Zheng, Chunfu; He, Sudan

2016-01-15

Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Meningitic Escherichia coli K1 penetration and neutrophil transmigration across the blood-brain barrier are modulated by alpha7 nicotinic receptor.

PubMed

Chi, Feng; Wang, Lin; Zheng, Xueye; Wu, Chun-Hua; Jong, Ambrose; Sheard, Michael A; Shi, Wei; Huang, Sheng-He

2011-01-01

Alpha7 nicotinic acetylcholine receptor (nAChR), an essential regulator of inflammation, is abundantly expressed in hippocampal neurons, which are vulnerable to bacterial meningitis. However, it is unknown whether α7 nAChR contributes to the regulation of these events. In this report, an aggravating role of α7 nAChR in host defense against meningitic E. coli infection was demonstrated by using α7-deficient (α7(-/-)) mouse brain microvascular endothelial cells (BMEC) and animal model systems. As shown in our in vitro and in vivo studies, E. coli K1 invasion and polymorphonuclear neutrophil (PMN) transmigration across the blood-brain barrier (BBB) were significantly reduced in α7(-/-) BMEC and α7(-/-) mice. Stimulation by nicotine was abolished in the α7(-/-) cells and animals. The same blocking effect was achieved by methyllycaconitine (α7 antagonist). The tight junction molecules occludin and ZO-1 were significantly reduced in the brain cortex of wildtype mice infected with E. coli and treated with nicotine, compared to α7(-/-) cells and animals. Decreased neuronal injury in the hippocampal dentate gyrus was observed in α7(-/-) mice with meningitis. Proinflammatory cytokines (IL-1β, IL-6, TNFα, MCP-1, MIP-1alpha, and RANTES) and adhesion molecules (CD44 and ICAM-1) were significantly reduced in the cerebrospinal fluids of the α7(-/-) mice with E. coli meningitis. Furthermore, α7 nAChR is the major calcium channel for nicotine- and E. coli K1-increased intracellular calcium concentrations of mouse BMEC. Taken together, our data suggest that α7 nAChR plays a detrimental role in the host defense against meningitic infection by modulation of pathogen invasion, PMN recruitment, calcium signaling and neuronal inflammation.

Meningitic Escherichia coli K1 Penetration and Neutrophil Transmigration Across the Blood–Brain Barrier are Modulated by Alpha7 Nicotinic Receptor

PubMed Central

Zheng, Xueye; Wu, Chun-Hua; Jong, Ambrose; Sheard, Michael A.; Shi, Wei; Huang, Sheng-He

2011-01-01

Alpha7 nicotinic acetylcholine receptor (nAChR), an essential regulator of inflammation, is abundantly expressed in hippocampal neurons, which are vulnerable to bacterial meningitis. However, it is unknown whether α7 nAChR contributes to the regulation of these events. In this report, an aggravating role of α7 nAChR in host defense against meningitic E. coli infection was demonstrated by using α7-deficient (α7-/-) mouse brain microvascular endothelial cells (BMEC) and animal model systems. As shown in our in vitro and in vivo studies, E. coli K1 invasion and polymorphonuclear neutrophil (PMN) transmigration across the blood-brain barrier (BBB) were significantly reduced in α7-/- BMEC and α7-/- mice. Stimulation by nicotine was abolished in the α7-/- cells and animals. The same blocking effect was achieved by methyllycaconitine (α7 antagonist). The tight junction molecules occludin and ZO-1 were significantly reduced in the brain cortex of wildtype mice infected with E. coli and treated with nicotine, compared to α7-/- cells and animals. Decreased neuronal injury in the hippocampal dentate gyrus was observed in α7-/- mice with meningitis. Proinflammatory cytokines (IL-1β, IL-6, TNFα, MCP-1, MIP-1alpha, and RANTES) and adhesion molecules (CD44 and ICAM-1) were significantly reduced in the cerebrospinal fluids of the α7-/- mice with E. coli meningitis. Furthermore, α7 nAChR is the major calcium channel for nicotine- and E. coli K1-increased intracellular calcium concentrations of mouse BMEC. Taken together, our data suggest that α7 nAChR plays a detrimental role in the host defense against meningitic infection by modulation of pathogen invasion, PMN recruitment, calcium signaling and neuronal inflammation. PMID:21966399

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.

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

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, ...

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...

Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia

PubMed Central

Silva, Ricardo Jorge; Cruz, Ana Rita; Mano, Miguel

2017-01-01

MicroRNAs play an important role in the interplay between bacterial pathogens and host cells, participating as host defense mechanisms, as well as exploited by bacteria to subvert host cellular functions. Here, we show that microRNAs modulate infection by Shigella flexneri, a major causative agent of bacillary dysentery in humans. Specifically, we characterize the dual regulatory role of miR-29b-2-5p during infection, showing that this microRNA strongly favors Shigella infection by promoting both bacterial binding to host cells and intracellular replication. Using a combination of transcriptome analysis and targeted high-content RNAi screening, we identify UNC5C as a direct target of miR-29b-2-5p and show its pivotal role in the modulation of Shigella binding to host cells. MiR-29b-2-5p, through repression of UNC5C, strongly enhances filopodia formation thus increasing Shigella capture and promoting bacterial invasion. The increase of filopodia formation mediated by miR-29b-2-5p is dependent on RhoF and Cdc42 Rho-GTPases. Interestingly, the levels of miR-29b-2-5p, but not of other mature microRNAs from the same precursor, are decreased upon Shigella replication at late times post-infection, through degradation of the mature microRNA by the exonuclease PNPT1. While the relatively high basal levels of miR-29b-2-5p at the start of infection ensure efficient Shigella capture by host cell filopodia, dampening of miR-29b-2-5p levels later during infection may constitute a bacterial strategy to favor a balanced intracellular replication to avoid premature cell death and favor dissemination to neighboring cells, or alternatively, part of the host response to counteract Shigella infection. Overall, these findings reveal a previously unappreciated role of microRNAs, and in particular miR-29b-2-5p, in the interaction of Shigella with host cells. PMID:28394930

Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia.

PubMed

Sunkavalli, Ushasree; Aguilar, Carmen; Silva, Ricardo Jorge; Sharan, Malvika; Cruz, Ana Rita; Tawk, Caroline; Maudet, Claire; Mano, Miguel; Eulalio, Ana

2017-04-01

MicroRNAs play an important role in the interplay between bacterial pathogens and host cells, participating as host defense mechanisms, as well as exploited by bacteria to subvert host cellular functions. Here, we show that microRNAs modulate infection by Shigella flexneri, a major causative agent of bacillary dysentery in humans. Specifically, we characterize the dual regulatory role of miR-29b-2-5p during infection, showing that this microRNA strongly favors Shigella infection by promoting both bacterial binding to host cells and intracellular replication. Using a combination of transcriptome analysis and targeted high-content RNAi screening, we identify UNC5C as a direct target of miR-29b-2-5p and show its pivotal role in the modulation of Shigella binding to host cells. MiR-29b-2-5p, through repression of UNC5C, strongly enhances filopodia formation thus increasing Shigella capture and promoting bacterial invasion. The increase of filopodia formation mediated by miR-29b-2-5p is dependent on RhoF and Cdc42 Rho-GTPases. Interestingly, the levels of miR-29b-2-5p, but not of other mature microRNAs from the same precursor, are decreased upon Shigella replication at late times post-infection, through degradation of the mature microRNA by the exonuclease PNPT1. While the relatively high basal levels of miR-29b-2-5p at the start of infection ensure efficient Shigella capture by host cell filopodia, dampening of miR-29b-2-5p levels later during infection may constitute a bacterial strategy to favor a balanced intracellular replication to avoid premature cell death and favor dissemination to neighboring cells, or alternatively, part of the host response to counteract Shigella infection. Overall, these findings reveal a previously unappreciated role of microRNAs, and in particular miR-29b-2-5p, in the interaction of Shigella with host cells.

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

Genome-Wide Transcriptional Response of Silkworm (Bombyx mori) to Infection by the Microsporidian Nosema bombycis

PubMed Central

Pan, Guoqing; Li, Zhihong; Han, Bing; Xu, Jinshan; Lan, Xiqian; Chen, Jie; Yang, Donglin; Chen, Quanmei; Sang, Qi; Ji, Xiaocun; Li, Tian; Long, Mengxian; Zhou, Zeyang

2013-01-01

Microsporidia have attracted much attention because they infect a variety of species ranging from protists to mammals, including immunocompromised patients with AIDS or cancer. Aside from the study on Nosema ceranae, few works have focused on elucidating the mechanism in host response to microsporidia infection. Nosema bombycis is a pathogen of silkworm pébrine that causes great economic losses to the silkworm industry. Detailed understanding of the host (Bombyx mori) response to infection by N. bombycis is helpful for prevention of this disease. A genome-wide survey of the gene expression profile at 2, 4, 6 and 8 days post-infection by N. bombycis was performed and results showed that 64, 244, 1,328, 1,887 genes were induced, respectively. Up to 124 genes, which are involved in basal metabolism pathways, were modulated. Notably, B. mori genes that play a role in juvenile hormone synthesis and metabolism pathways were induced, suggesting that the host may accumulate JH as a response to infection. Interestingly, N. bombycis can inhibit the silkworm serine protease cascade melanization pathway in hemolymph, which may be due to the secretion of serpins in the microsporidia. N. bombycis also induced up-regulation of several cellular immune factors, in which CTL11 has been suggested to be involved in both spore recognition and immune signal transduction. Microarray and real-time PCR analysis indicated the activation of silkworm Toll and JAK/STAT pathways. The notable up-regulation of antimicrobial peptides, including gloverins, lebocins and moricins, strongly indicated that antimicrobial peptide defense mechanisms were triggered to resist the invasive microsporidia. An analysis of N. bombycis-specific response factors suggested their important roles in anti-microsporidia defense. Overall, this study primarily provides insight into the potential molecular mechanisms for the host-parasite interaction between B. mori and N. bombycis and may provide a foundation for further work on host-parasite interaction between insects and microsporidia. PMID:24386341

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 with high intraspecific variation. Behavioral patterns as well as specific features of these ant-parasitoid interactions are described, and their ecological importance discussed. PMID:23448343

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 cell death and immunity signaling.

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.

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.

Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

PubMed

Rodríguez Pulido, Miguel; Sáiz, Margarita

2017-01-01

Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

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

A common origin for immunity and digestion.

PubMed

Broderick, Nichole A

2015-01-01

Historically, the digestive and immune systems were viewed and studied as separate entities. However, there are remarkable similarities and shared functions in both nutrient acquisition and host defense. Here, I propose a common origin for both systems. This association provides a new prism for viewing the emergence and evolution of host defense mechanisms.

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...

ENHANCED BINDING OF AUTOLOGOUS RED CELLS TO THE MACROPHAGE PLASMA MEMBRANE AS A SENSITIVE INDICATOR OF POLLUTANT DAMAGE

EPA Science Inventory

The alveolar macrophage (AM) represents the primary line of defense in host protection against inhaled infectious organisms. Following exposure to oxidant gases, the ability of the host to resist airborne bacterial infection is severely impaired, and damage to the AM defense syst...

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.

PPARγ in Bacterial Infections: A Friend or Foe?

PubMed

Reddy, Aravind T; Lakshmi, Sowmya P; Reddy, Raju C

2016-01-01

Peroxisome proliferator-activated receptor γ (PPAR γ ) is now recognized as an important modulator of leukocyte inflammatory responses and function. Its immunoregulatory function has been studied in a variety of contexts, including bacterial infections of the lungs and central nervous system, sepsis, and conditions such as chronic granulomatous disease. Although it is generally believed that PPAR γ activation is beneficial for the host during bacterial infections via its anti-inflammatory and antibacterial properties, PPAR γ agonists have also been shown to dampen the host immune response and in some cases exacerbate infection by promoting leukocyte apoptosis and interfering with leukocyte migration and infiltration. In this review we discuss the role of PPAR γ and its activation during bacterial infections, with focus on the potential of PPAR γ agonists and perhaps antagonists as novel therapeutic modalities. We conclude that adjustment in the dosage and timing of PPAR γ agonist administration, based on the competence of host antimicrobial defenses and the extent of inflammatory response and tissue injury, is critical for achieving the essential balance between pro- and anti-inflammatory effects on the immune system.

PPARγ in Bacterial Infections: A Friend or Foe?

PubMed Central

2016-01-01

Peroxisome proliferator-activated receptor γ (PPARγ) is now recognized as an important modulator of leukocyte inflammatory responses and function. Its immunoregulatory function has been studied in a variety of contexts, including bacterial infections of the lungs and central nervous system, sepsis, and conditions such as chronic granulomatous disease. Although it is generally believed that PPARγ activation is beneficial for the host during bacterial infections via its anti-inflammatory and antibacterial properties, PPARγ agonists have also been shown to dampen the host immune response and in some cases exacerbate infection by promoting leukocyte apoptosis and interfering with leukocyte migration and infiltration. In this review we discuss the role of PPARγ and its activation during bacterial infections, with focus on the potential of PPARγ agonists and perhaps antagonists as novel therapeutic modalities. We conclude that adjustment in the dosage and timing of PPARγ agonist administration, based on the competence of host antimicrobial defenses and the extent of inflammatory response and tissue injury, is critical for achieving the essential balance between pro- and anti-inflammatory effects on the immune system. PMID:27774097

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.

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

The Sinorhizobium (Ensifer) fredii HH103 Type 3 Secretion System Suppresses Early Defense Responses to Effectively Nodulate Soybean.

PubMed

Jiménez-Guerrero, Irene; Pérez-Montaño, Francisco; Monreal, José Antonio; Preston, Gail M; Fones, Helen; Vioque, Blanca; Ollero, Francisco Javier; López-Baena, Francisco Javier

2015-07-01

Plants that interact with pathogenic bacteria in their natural environments have developed barriers to block or contain the infection. Phytopathogenic bacteria have evolved mechanisms to subvert these defenses and promote infection. Thus, the type 3 secretion system (T3SS) delivers bacterial effectors directly into the plant cells to alter host signaling and suppress defenses, providing an appropriate environment for bacterial multiplication. Some rhizobial strains possess a symbiotic T3SS that seems to be involved in the suppression of host defenses to promote nodulation and determine the host range. In this work, we show that the inactivation of the Sinorhizobium (Ensifer) fredii HH103 T3SS negatively affects soybean nodulation in the early stages of the symbiotic process, which is associated with a reduction of the expression of early nodulation genes. This symbiotic phenotype could be the consequence of the bacterial triggering of soybean defense responses associated with the production of salicylic acid (SA) and the impairment of the T3SS mutant to suppress these responses. Interestingly, the early induction of the transcription of GmMPK4, which negatively regulates SA accumulation and defense responses in soybean via WRKY33, could be associated with the differential defense responses induced by the parental and the T3SS mutant strain.

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.

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

Deployment of the Burkholderia glumae type III secretion system as an efficient tool for translocating pathogen effectors to monocot cells.

PubMed

Sharma, Shailendra; Sharma, Shiveta; Hirabuchi, Akiko; Yoshida, Kentaro; Fujisaki, Koki; Ito, Akiko; Uemura, Aiko; Terauchi, Ryohei; Kamoun, Sophien; Sohn, Kee Hoon; Jones, Jonathan D G; Saitoh, Hiromasa

2013-05-01

Genome sequences of plant fungal pathogens have enabled the identification of effectors that cooperatively modulate the cellular environment for successful fungal growth and suppress host defense. Identification and characterization of novel effector proteins are crucial for understanding pathogen virulence and host-plant defense mechanisms. Previous reports indicate that the Pseudomonas syringae pv. tomato DC3000 type III secretion system (T3SS) can be used to study how non-bacterial effectors manipulate dicot plant cell function using the effector detector vector (pEDV) system. Here we report a pEDV-based effector delivery system in which the T3SS of Burkholderia glumae, an emerging rice pathogen, is used to translocate the AVR-Pik and AVR-Pii effectors of the fungal pathogen Magnaporthe oryzae to rice cytoplasm. The translocated AVR-Pik and AVR-Pii showed avirulence activity when tested in rice cultivars containing the cognate R genes. AVR-Pik reduced and delayed the hypersensitive response triggered by B. glumae in the non-host plant Nicotiana benthamiana, indicative of an immunosuppressive virulence activity. AVR proteins fused with fluorescent protein and nuclear localization signal were delivered by B. glumae T3SS and observed in the nuclei of infected cells in rice, wheat, barley and N. benthamiana. Our bacterial T3SS-enabled eukaryotic effector delivery and subcellular localization assays provide a useful method for identifying and studying effector functions in monocot plants. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Entamoeba histolytica L220 induces the in vitro activation of macrophages and neutrophils and is modulated by neurotransmitters.

PubMed

Villalobos-Gómez, Fabiola Del Rocío; García-Lorenzana, Mario; Escobedo, Galileo; Talamás-Rohana, Patricia; Salinas-Gutiérrez, Rogelio; Hernández-Ramírez, Verónica-Ivonne; Sánchez-Alemán, Esperanza; Campos-Esparza, María Del Rosario; Muñoz-Ortega, Martín Humberto; Ventura-Juárez, Javier

2018-06-26

The neuroimmunoregulation of inflammation has been well characterized. Entamoeba histolytica provokes an inflammatory response in the host in which macrophages and neutrophils are the first line of defense. The aim of this study was to analyze the effect of the 220 kDa lectin of Entamoeba histolytica on stimulation of human macrophages and neutrophils, especially the secretion of cytokines and the relation of these to neurotransmitters. Human cells were interacted with L220, epinephrine, nicotine, esmolol and vecuronium bromide. The concentrations of IL-1β, IFN-γ, TNF-α and IL-10 were determined by ELISA at, 4 h of interaction. L220 has a cytokine stimulating function of macrophages and neutrophils for secretion of IL-1β, and IL-10 only by macrophages, which was modulated by the effect of vecuronium on cholinergic receptors in this immune cells.

African swine fever virus (ASFV) protection mediated by NH/P68 and NH/P68 recombinant live-attenuated viruses.

PubMed

Gallardo, Carmina; Sánchez, Elena G; Pérez-Núñez, Daniel; Nogal, Marisa; de León, Patricia; Carrascosa, Ángel L; Nieto, Raquel; Soler, Alejandro; Arias, María Luisa; Revilla, Yolanda

2018-05-03

The risk of spread of African swine fever virus (ASFV) from Russia and Caucasian areas to several EU countries has recently emerged, making it imperative to improve our knowledge and defensive tools against this important pathogen. The ASFV genome encodes many genes which are not essential for virus replication but are known to control host immune evasion, such as NFκB and the NFAT regulator A238L, the apoptosis inhibitor A224L, the MHC-I antigen presenting modulator EP153R, and the A276R gene, involved in modulating type I IFN. These genes are hypothesized to be involved in virulence of the genotype I parental ASFV NH/P68. We here describe the generation of putative live attenuated vaccines (LAV) prototypes by constructing recombinant NH/P68 viruses lacking these specific genes and containing specific markers. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

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

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.

Fusarium oxysporum f.sp. ciceri Race 1 Induced Redox State Alterations Are Coupled to Downstream Defense Signaling in Root Tissues of Chickpea (Cicer arietinum L.)

PubMed Central

Chatterjee, Moniya; Das, Sampa

2013-01-01

Reactive oxygen species are known to play pivotal roles in pathogen perception, recognition and downstream defense signaling. But, how these redox alarms coordinate in planta into a defensive network is still intangible. Present study illustrates the role of Fusarium oxysporum f.sp ciceri Race1 (Foc1) induced redox responsive transcripts in regulating downstream defense signaling in chickpea. Confocal microscopic studies highlighted pathogen invasion and colonization accompanied by tissue damage and deposition of callose degraded products at the xylem vessels of infected roots of chickpea plants. Such depositions led to the clogging of xylem vessels in compatible hosts while the resistant plants were devoid of such obstructions. Lipid peroxidation assays also indicated fungal induced membrane injury. Cell shrinkage and gradual nuclear adpression appeared as interesting features marking fungal ingress. Quantitative real time polymerase chain reaction exhibited differential expression patterns of redox regulators, cellular transporters and transcription factors during Foc1 progression. Network analysis showed redox regulators, cellular transporters and transcription factors to coordinate into a well orchestrated defensive network with sugars acting as internal signal modulators. Respiratory burst oxidase homologue, cationic peroxidase, vacuolar sorting receptor, polyol transporter, sucrose synthase, and zinc finger domain containing transcription factor appeared as key molecular candidates controlling important hubs of the defense network. Functional characterization of these hub controllers may prove to be promising in understanding chickpea–Foc1 interaction and developing the case study as a model for looking into the complexities of wilt diseases of other important crop legumes. PMID:24058463

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 dominance. Adaptation to host immune responses while maintaining a partially active host immunity seems advantageous against competitors. We suggest a model for future research that considers not only host–microbe but in addition microbe–microbe and microbe–host environment factors. PMID:27379119

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

Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

PubMed Central

Bidula, Stefan; Kenawy, Hany; Ali, Youssif M.; Sexton, Darren; Schwaeble, Wilhelm J.

2013-01-01

Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A. PMID:23478320

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.

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.

Recent insights into plant-virus interactions through proteomic analysis.

PubMed

Di Carli, Mariasole; Benvenuto, Eugenio; Donini, Marcello

2012-10-05

Plant viruses represent a major threat for a wide range of host species causing severe losses in agricultural practices. The full comprehension of mechanisms underlying events of virus-host plant interaction is crucial to devise novel plant resistance strategies. Until now, functional genomics studies in plant-virus interaction have been limited mainly on transcriptomic analysis. Only recently are proteomic approaches starting to provide important contributions to this area of research. Classical two-dimensional electrophoresis (2-DE) coupled to mass spectrometry (MS) is still the most widely used platform in plant proteome analysis, although in the last years the application of quantitative "second generation" proteomic techniques (such as differential in gel electrophoresis, DIGE, and gel-free protein separation methods) are emerging as more powerful analytical approaches. Apparently simple, plant-virus interactions reveal a really complex pathophysiological context, in which resistance, defense and susceptibility, and direct virus-induced reactions interplay to trigger expression responses of hundreds of genes. Given that, this review is specifically focused on comparative proteome-based studies on pathogenesis of several viral genera, including some of the most important and widespread plant viruses of the genus Tobamovirus, Sobemovirus, Cucumovirus and Potyvirus. In all, this overview reveals a widespread repression of proteins associated with the photosynthetic apparatus, while energy metabolism/protein synthesis and turnover are typically up-regulated, indicating a major redirection of cell metabolism. Other common features include the modulation of metabolisms concerning sugars, cell wall, and reactive oxigen species as well as pathogenesis-related (PR) proteins. The fine-tuning between plant development and antiviral defense mechanisms determines new patterns of regulation of common metabolic pathways. By offering a 360-degree view of protein modulation, all proteomic tools reveal the extraordinary intricacy of mechanisms with which a simple viral genome perturbs the plant cell molecular networks. This "omic" approach, while providing a global perspective and useful information to the understanding of the plant host-virus interactome, may possibly reveal protein targets/markers useful in the design of future diagnosis and/or plant protection strategies.

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

Immunonutrition in Critical Illness: What Is the Role?

PubMed

McCarthy, Mary S; Martindale, Robert G

2018-06-01

Acute illness-associated malnutrition leads to muscle wasting, delayed wound healing, failure to wean from ventilator support, and possibly higher rates of infection and longer hospital stays unless appropriate metabolic support is provided in the form of nutrition therapy. Agreement is still lacking about the value of individual immune-modulating substrates for specific patient populations. However, it has long been agreed that there are 3 primary targets for these substrates: 1) mucosal barrier function, 2) cellular defense function, and 3) local and systemic inflammation. These targets guide the multitude of interventions necessary to stabilize and treat the hypercatabolic intensive care unit patient, including specialized nutrition therapy. The paradigm shift that occurred 30 years ago created a unique role for nutrition as an agent to support host defense mechanisms and prevent infectious complications in the critically ill patient. This overview of immunonutrition will discuss the evidence for its role in critical illness today. © 2018 American Society for Parenteral and Enteral Nutrition.

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

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.

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 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

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.

Struggle for space: viral extinction through competition for cells.

PubMed

Cuesta, José A; Aguirre, Jacobo; Capitán, José A; Manrubia, Susanna C

2011-01-14

The design of protocols to suppress the propagation of viral infections is an enduring enterprise, especially hindered by limited knowledge of the mechanisms leading to viral extinction. Here we report on infection extinction due to intraspecific competition to infect susceptible hosts. Beneficial mutations increase the production of viral progeny, while the host cell may develop defenses against infection. For an unlimited number of host cells, a feedback runaway coevolution between host resistance and progeny production occurs. However, physical space limits the advantage that the virus obtains from increasing offspring numbers; thus, infection clearance may result from an increase in host defenses beyond a finite threshold. Our results might be relevant to devise improved control strategies in environments with mobility constraints or different geometrical properties.

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.

Antimicrobial peptides and induced membrane curvature: geometry, coordination chemistry, and molecular engineering

PubMed Central

Schmidt, Nathan W.; Wong, Gerard C. L.

2013-01-01

Short cationic, amphipathic antimicrobial peptides are multi-functional molecules that have roles in host defense as direct microbicides and modulators of the immune response. While a general mechanism of microbicidal activity involves the selective disruption and permeabilization of cell membranes, the relationships between peptide sequence and membrane activity are still under investigation. Here, we review the diverse functions that AMPs collectively have in host defense, and show that these functions can be multiplexed with a membrane mechanism of activity derived from the generation of negative Gaussian membrane curvature. As AMPs preferentially generate this curvature in model bacterial cell membranes, the selective generation of negative Gaussian curvature provides AMPs with a broad mechanism to target microbial membranes. The amino acid constraints placed on AMPs by the geometric requirement to induce negative Gaussian curvature are consistent with known AMP sequences. This ‘saddle-splay curvature selection rule’ is not strongly restrictive so AMPs have significant compositional freedom to multiplex membrane activity with other useful functions. The observation that certain proteins involved in cellular processes which require negative Gaussian curvature contain domains with similar motifs as AMPs, suggests this rule may be applicable to other curvature-generating proteins. Since our saddle-splay curvature design rule is based upon both a mechanism of activity and the existing motifs of natural AMPs, we believe it will assist the development of synthetic antimicrobials. PMID:24778573

Three-way interaction among plants, bacteria, and coleopteran insects.

PubMed

Wielkopolan, Beata; Obrępalska-Stęplowska, Aleksandra

2016-08-01

Coleoptera, the largest and the most diverse Insecta order, is characterized by multiple adaptations to plant feeding. Insect-associated microorganisms can be important mediators and modulators of interactions between insects and plants. Interactions between plants and insects are highly complex and involve multiple factors. There are various defense mechanisms initiated by plants upon attack by herbivorous insects, including the development of morphological structures and the synthesis of toxic secondary metabolites and volatiles. In turn, herbivores have adapted to feeding on plants and further sophisticated adaptations to overcome plant responses may continue to evolve. Herbivorous insects may detoxify toxic phytocompounds, sequester poisonous plant factors, and alter their own overall gene expression pattern. Moreover, insects are associated with microbes, which not only considerably affect insects, but can also modify plant defense responses to the benefit of their host. Plants are also frequently associated with endophytes, which may act as bioinsecticides. Therefore, it is very important to consider the factors influencing the interaction between plants and insects. Herbivorous insects cause considerable damage to global crop production. Coleoptera is the largest and the most diverse order in the class Insecta. In this review, various aspects of the interactions among insects, microbes, and plants are described with a focus on coleopteran species, their bacterial symbionts, and their plant hosts to demonstrate that many factors contribute to the success of coleopteran herbivory.

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

PubMed Central

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

2011-01-01

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

Early-Life Diet Affects Host Microbiota and Later-Life Defenses Against Parasites in Frogs.

PubMed

Knutie, Sarah A; Shea, Lauren A; Kupselaitis, Marinna; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

2017-10-01

Food resources can affect the health of organisms by altering their symbiotic microbiota and affecting energy reserves for host defenses against parasites. Different diets can vary in their macronutrient content and therefore they might favor certain bacterial communities of the host and affect the development and maintenance of the immune system, such as the inflammatory or antibody responses. Thus, testing the effect of diet, especially for animals with wide diet breadths, on host-associated microbiota and defenses against parasites might be important in determining infection and disease risk. Here, we test whether the early-life diet of Cuban tree frogs (Osteopilus septentrionalis) affects early- and later-life microbiota as well as later-life defenses against skin-penetrating, gut worms (Aplectana hamatospicula). We fed tadpoles two ecologically common diets: a diet of conspecifics or a diet of algae (Arthrospira sp.). We then: (1) characterized the gut microbiota of tadpoles and adults; and (2) challenged adult frogs with parasitic worms and measured host resistance (including the antibody-mediated immune response) and tolerance of infections. Tadpole diet affected bacterial communities in the guts of tadpoles but did not have enduring effects on the bacterial communities of adults. In contrast, tadpole diet had enduring effects on host resistance and tolerance of infections in adult frogs. Frogs that were fed a conspecific-based diet as tadpoles were more resistant to worm penetration compared with frogs that were fed an alga-based diet as tadpoles, but less resistant to worm establishment, which may be related to their suppressed antibody response during worm establishment. Furthermore, frogs that were fed a conspecific-based diet as tadpoles were more tolerant to the effect of parasite abundance on host mass during worm establishment. Overall, our study demonstrates that the diet of Cuban tree frog tadpoles affects the gut microbiota and defenses against parasitic gut worms of frogs, but these effects depend on the stage of the host and infection, respectively. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

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

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.

Mast cell: an emerging partner in immune interaction.

PubMed

Gri, Giorgia; Frossi, Barbara; D'Inca, Federica; Danelli, Luca; Betto, Elena; Mion, Francesca; Sibilano, Riccardo; Pucillo, Carlo

2012-01-01

Mast cells (MCs) are currently recognized as effector cells in many settings of the immune response, including host defense, immune regulation, allergy, chronic inflammation, and autoimmune diseases. MC pleiotropic functions reflect their ability to secrete a wide spectrum of preformed or newly synthesized biologically active products with pro-inflammatory, anti-inflammatory and/or immunosuppressive properties, in response to multiple signals. Moreover, the modulation of MC effector phenotypes relies on the interaction of a wide variety of membrane molecules involved in cell-cell or cell-extracellular-matrix interaction. The delivery of co-stimulatory signals allows MC to specifically communicate with immune cells belonging to both innate and acquired immunity, as well as with non-immune tissue-specific cell types. This article reviews and discusses the evidence that MC membrane-expressed molecules play a central role in regulating MC priming and activation and in the modulation of innate and adaptive immune response not only against host injury, but also in peripheral tolerance and tumor-surveillance or -escape. The complex expression of MC surface molecules may be regarded as a measure of connectivity, with altered patterns of cell-cell interaction representing functionally distinct MC states. We will focalize our attention on roles and functions of recently discovered molecules involved in the cross-talk of MCs with other immune partners.

Mast Cell: An Emerging Partner in Immune Interaction

PubMed Central

Gri, Giorgia; Frossi, Barbara; D’Inca, Federica; Danelli, Luca; Betto, Elena; Mion, Francesca; Sibilano, Riccardo; Pucillo, Carlo

2012-01-01

Mast cells (MCs) are currently recognized as effector cells in many settings of the immune response, including host defense, immune regulation, allergy, chronic inflammation, and autoimmune diseases. MC pleiotropic functions reflect their ability to secrete a wide spectrum of preformed or newly synthesized biologically active products with pro-inflammatory, anti-inflammatory and/or immunosuppressive properties, in response to multiple signals. Moreover, the modulation of MC effector phenotypes relies on the interaction of a wide variety of membrane molecules involved in cell–cell or cell-extracellular-matrix interaction. The delivery of co-stimulatory signals allows MC to specifically communicate with immune cells belonging to both innate and acquired immunity, as well as with non-immune tissue-specific cell types. This article reviews and discusses the evidence that MC membrane-expressed molecules play a central role in regulating MC priming and activation and in the modulation of innate and adaptive immune response not only against host injury, but also in peripheral tolerance and tumor-surveillance or -escape. The complex expression of MC surface molecules may be regarded as a measure of connectivity, with altered patterns of cell–cell interaction representing functionally distinct MC states. We will focalize our attention on roles and functions of recently discovered molecules involved in the cross-talk of MCs with other immune partners. PMID:22654879

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

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.

Unraveling incompatibility between wheat and the fungal pathogen Zymoseptoria tritici through apoplastic proteomics.

PubMed

Yang, Fen; Li, Wanshun; Derbyshire, Mark; Larsen, Martin R; Rudd, Jason J; Palmisano, Giuseppe

2015-05-08

Hemibiotrophic fungal pathogen Zymoseptoria tritici causes severe foliar disease in wheat. However, current knowledge of molecular mechanisms involved in plant resistance to Z. tritici and Z. tritici virulence factors is far from being complete. The present work investigated the proteome of leaf apoplastic fluid with emphasis on both host wheat and Z. tritici during the compatible and incompatible interactions. The proteomics analysis revealed rapid host responses to the biotrophic growth, including enhanced carbohydrate metabolism, apoplastic defenses and stress, and cell wall reinforcement, might contribute to resistance. Compatibility between the host and the pathogen was associated with inactivated plant apoplastic responses as well as fungal defenses to oxidative stress and perturbation of plant cell wall during the initial biotrophic stage, followed by the strong induction of plant defenses during the necrotrophic stage. To study the role of anti-oxidative stress in Z. tritici pathogenicity in depth, a YAP1 transcription factor regulating antioxidant expression was deleted and showed the contribution to anti-oxidative stress in Z. tritici, but was not required for pathogenicity. This result suggests the functional redundancy of antioxidants in the fungus. The data demonstrate that incompatibility is probably resulted from the proteome-level activation of host apoplastic defenses as well as fungal incapability to adapt to stress and interfere with host cell at the biotrophic stage of the interaction.

Toll-like receptor signaling: a perspective to develop vaccine against leishmaniasis.

PubMed

Singh, Rakesh K; Srivastava, Ankita; Singh, Nisha

2012-09-06

The toll-like receptors (TLRs) are the sentinel factor of the innate immunity, which are essential for host defense. These receptors detect the presence of conserved molecular patterns of potentially pathogenic microorganisms and contribute in both, cellular as well as humoral immune responses. Leishmania is an intracellular pathogen that silently invades host immune system. After phagocytosis, it divides and proliferates in the harmful environment of host macrophages by down-regulating its vital effector functions. In leishmaniasis, the outcome of the infection basically relies on the skewed balance between Th1/Th2 immune responses. Lots of work have been done and on progress but still characterization of either preventive or prophylactic candidate antigen/s is far from satisfactory. How does Leishmania regulate host innate immune system? Still it is unanswered. TLRs play very important role during inflammatory process of various diseases such as cancer, bacterial and viral infections but TLR signaling is comparatively less explained in leishmanial infection. In the context to Th1/Th2 dichotomy, identification of leishmanial antigens that modulate toll-like receptor signaling will certainly help in the development of future vaccine. This review will initially describe global properties of TLRs, and later will discuss their role in the pathogenesis of leishmaniasis. Copyright © 2012 Elsevier GmbH. All rights reserved.

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2013-03-20

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2013-0018] Request for Information (RFI) Regarding the Planned Biotechnology Development Module (BDM) As Part of the National Bio and Agro-Defense... Development Module (BDM) a planned component of the National Bio and Agro-Defense Facility (NBAF) and...

Hypoglycemic depression of RES function.

PubMed

Buchanan, B J; Filkins, J P

1976-07-01

The intravascular removal rates of colloidal carbon and of biologically active endotoxin by the reticuloendothelial system (RES) were evaluated as a function of blood-glucose levels. There was a significant negative correlation of carbon clearance half time on blood glucose in both saline-treated and insulin-treated rats. Insulin hypoglycemia depressed RES carbon clearance with the maximal effect occurring at blood glucose values below 30 mg/dl. Insulin hypoglycemia also severely impaired the intravascular removal of endotoxin as evaluated by lethality bioassay in lead-sensitized rats. It is concluded that blood glucose may modulate RES phagocytic function and that the hypoglycemia of endotoxin shock may augment the shock state due to impairment of RES host defense clearance functions.

Bench-to-bedside review: Toll-like receptors and their role in septic shock

PubMed Central

Opal, Steven M; Huber, Christian E

2002-01-01

The Toll-like receptors (TLRs) are essential transmembrane signaling receptors of the innate immune system that alert the host to the presence of a microbial invader. The recent discovery of the TLRs has rapidly expanded our knowledge of molecular events that initiate host–pathogen interactions. These functional attributes of the cellular receptors provide insights into the nature of pattern recognition receptors that activate the human antimicrobial defense systems. The fundamental significance of the TLRs in the generation of systemic inflammation and the pathogenesis of septic shock is reviewed. The potential clinical implications of therapeutic modulation of these recently characterized receptors of innate immunity are also discussed. PMID:11983038

Toll-like receptor activation by helminths or helminth products to alleviate inflammatory bowel disease.

PubMed

Sun, ShuMin; Wang, XueLin; Wu, XiuPing; Zhao, Ying; Wang, Feng; Liu, XiaoLei; Song, Yanxia; Wu, ZhiLiang; Liu, MingYuan

2011-09-27

Helminth infection may modulate the expression of Toll like receptors (TLR) in dendritic cells (DCs) and modify the responsiveness of DCs to TLR ligands. This may regulate aberrant intestinal inflammation in humans with helminthes and may thus help alleviate inflammation associated with human inflammatory bowel disease (IBD). Epidemiological and experimental data provide further evidence that reducing helminth infections increases the incidence rate of such autoimmune diseases. Fine control of inflammation in the TLR pathway is highly desirable for effective host defense. Thus, the use of antagonists of TLR-signaling and agonists of their negative regulators from helminths or helminth products should be considered for the treatment of IBD.

Toll-like receptor activation by helminths or helminth products to alleviate inflammatory bowel disease

PubMed Central

2011-01-01

Helminth infection may modulate the expression of Toll like receptors (TLR) in dendritic cells (DCs) and modify the responsiveness of DCs to TLR ligands. This may regulate aberrant intestinal inflammation in humans with helminthes and may thus help alleviate inflammation associated with human inflammatory bowel disease (IBD). Epidemiological and experimental data provide further evidence that reducing helminth infections increases the incidence rate of such autoimmune diseases. Fine control of inflammation in the TLR pathway is highly desirable for effective host defense. Thus, the use of antagonists of TLR-signaling and agonists of their negative regulators from helminths or helminth products should be considered for the treatment of IBD. PMID:21943110

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

PubMed

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

2014-10-07

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

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.

Male killing Spiroplasma protects Drosophila melanogaster against two parasitoid wasps

PubMed Central

Xie, J; Butler, S; Sanchez, G; Mateos, M

2014-01-01

Maternally transmitted associations between endosymbiotic bacteria and insects are diverse and widespread in nature. Owing to imperfect vertical transmission, many heritable microbes have evolved compensational mechanisms to enhance their persistence in host lineages, such as manipulating host reproduction and conferring fitness benefits to host. Symbiont-mediated defense against natural enemies of hosts is increasingly recognized as an important mechanism by which endosymbionts enhance host fitness. Members of the genus Spiroplasma associated with distantly related Drosophila hosts are known to engage in either reproductive parasitism (i.e., male killing) or defense against natural enemies (the parasitic wasp Leptopilina heterotoma and a nematode). A male-killing strain of Spiroplasma (strain Melanogaster Sex Ratio Organism (MSRO)) co-occurs with Wolbachia (strain wMel) in certain wild populations of the model organism Drosophila melanogaster. We examined the effects of Spiroplasma MSRO and Wolbachia wMel on Drosophila survival against parasitism by two common wasps, Leptopilina heterotoma and Leptopilina boulardi, that differ in their host ranges and host evasion strategies. The results indicate that Spiroplasma MSRO prevents successful development of both wasps, and confers a small, albeit significant, increase in larva-to-adult survival of flies subjected to wasp attacks. We modeled the conditions under which defense can contribute to Spiroplasma persistence. Wolbachia also confers a weak, but significant, survival advantage to flies attacked by L. heterotoma. The host protective effects exhibited by Spiroplasma and Wolbachia are additive and may provide the conditions for such cotransmitted symbionts to become mutualists. Occurrence of Spiroplasma-mediated protection against distinct parasitoids in divergent Drosophila hosts suggests a general protection mechanism. PMID:24281548

Boron Induces Lymphocyte Proliferation and Modulates the Priming Effects of Lipopolysaccharide on Macrophages.

PubMed

Routray, Indusmita; Ali, Shakir

2016-01-01

Chemical mediators of inflammation (CMI) are important in host defense against infection. The reduced capacity of host to induce the secretion of these mediators following infection is one of the factors in host susceptibility to infection. Boron, which has been suggested for its role in infection, is reported in this study to increase lymphocyte proliferation and the secretion of CMI by the lipopolysaccharide (LPS)-stimulated peritoneal macrophages in BALB/c mice. Boron was administered to mice orally as borax at different doses for 10 consecutive days, followed by the stimulation of animals with ovalbumin and isolation of splenocytes for proliferation assay. The lymphocyte subsets were determined by flow cytometry in spleen cell suspension. The mediators of inflammation, TNF-α, IL-6, IL-1β and nitric oxide (NO), were measured in culture supernatant of LPS-primed macrophages isolated from borax treated mice. TNF and ILs were measured by ELISA. NO was determined by Griess test. The expression of inducible nitric oxide synthase (iNOS) in macrophages was studied by confocal microscopy. Results showed a significant increase in T and B cell populations, as indicated by an increase in CD4 and CD19, but not CD8, cells. Boron further stimulated the secretion of TNF-α, IL-6, IL-1β, NO and the expression of iNOS by the LPS-primed macrophages. The effect was dose dependent and most significant at a dose level of 4.6 mg/kg b. wt. Taken together, the study concludes that boron at physiological concentration induces lymphocyte proliferation and increases the synthesis and secretion of pro-inflammatory mediators by the LPS-primed macrophages, more specifically the M1 macrophages, possibly acting through Toll-like receptor. The study implicates boron as a regulator of the immune and inflammatory reactions and macrophage polarization, thus playing an important role in augmenting host defense against infection, with possible role in cancer and other diseases.

Boron Induces Lymphocyte Proliferation and Modulates the Priming Effects of Lipopolysaccharide on Macrophages

PubMed Central

Routray, Indusmita; Ali, Shakir

2016-01-01

Chemical mediators of inflammation (CMI) are important in host defense against infection. The reduced capacity of host to induce the secretion of these mediators following infection is one of the factors in host susceptibility to infection. Boron, which has been suggested for its role in infection, is reported in this study to increase lymphocyte proliferation and the secretion of CMI by the lipopolysaccharide (LPS)-stimulated peritoneal macrophages in BALB/c mice. Boron was administered to mice orally as borax at different doses for 10 consecutive days, followed by the stimulation of animals with ovalbumin and isolation of splenocytes for proliferation assay. The lymphocyte subsets were determined by flow cytometry in spleen cell suspension. The mediators of inflammation, TNF-α, IL-6, IL-1β and nitric oxide (NO), were measured in culture supernatant of LPS-primed macrophages isolated from borax treated mice. TNF and ILs were measured by ELISA. NO was determined by Griess test. The expression of inducible nitric oxide synthase (iNOS) in macrophages was studied by confocal microscopy. Results showed a significant increase in T and B cell populations, as indicated by an increase in CD4 and CD19, but not CD8, cells. Boron further stimulated the secretion of TNF-α, IL-6, IL-1β, NO and the expression of iNOS by the LPS-primed macrophages. The effect was dose dependent and most significant at a dose level of 4.6 mg/kg b. wt. Taken together, the study concludes that boron at physiological concentration induces lymphocyte proliferation and increases the synthesis and secretion of pro-inflammatory mediators by the LPS-primed macrophages, more specifically the M1 macrophages, possibly acting through Toll-like receptor. The study implicates boron as a regulator of the immune and inflammatory reactions and macrophage polarization, thus playing an important role in augmenting host defense against infection, with possible role in cancer and other diseases. PMID:26934748

Serine Protease Inhibitors in Ticks: An Overview of Their Role in Tick Biology and Tick-Borne Pathogen Transmission.

PubMed

Blisnick, Adrien A; Foulon, Thierry; Bonnet, Sarah I

2017-01-01

New tick and tick-borne pathogen control approaches that are both environmentally sustainable and which provide broad protection are urgently needed. Their development, however, will rely on a greater understanding of tick biology, tick-pathogen, and tick-host interactions. The recent advances in new generation technologies to study genomes, transcriptomes, and proteomes has resulted in a plethora of tick biomacromolecular studies. Among these, many enzyme inhibitors have been described, notably serine protease inhibitors (SPIs), whose importance in various tick biological processes is only just beginning to be fully appreciated. Among the multiple active substances secreted during tick feeding, SPIs have been shown to be directly involved in regulation of inflammation, blood clotting, wound healing, vasoconstriction and the modulation of host defense mechanisms. In light of these activities, several SPIs were examined and were experimentally confirmed to facilitate tick pathogen transmission. In addition, to prevent coagulation of the ingested blood meal within the tick alimentary canal, SPIs are also involved in blood digestion and nutrient extraction from the meal. The presence of SPIs in tick hemocytes and their involvement in tick innate immune defenses have also been demonstrated, as well as their implication in hemolymph coagulation and egg development. Considering the involvement of SPIs in multiple crucial aspects of tick-host-pathogen interactions, as well as in various aspects of the tick parasitic lifestyle, these molecules represent highly suitable and attractive targets for the development of effective tick control strategies. Here we review the current knowledge regarding this class of inhibitors in tick biology and tick-borne pathogen transmission, and their potential as targets for future tick control trials.

Serine Protease Inhibitors in Ticks: An Overview of Their Role in Tick Biology and Tick-Borne Pathogen Transmission

PubMed Central

Blisnick, Adrien A.; Foulon, Thierry; Bonnet, Sarah I.

2017-01-01

New tick and tick-borne pathogen control approaches that are both environmentally sustainable and which provide broad protection are urgently needed. Their development, however, will rely on a greater understanding of tick biology, tick-pathogen, and tick-host interactions. The recent advances in new generation technologies to study genomes, transcriptomes, and proteomes has resulted in a plethora of tick biomacromolecular studies. Among these, many enzyme inhibitors have been described, notably serine protease inhibitors (SPIs), whose importance in various tick biological processes is only just beginning to be fully appreciated. Among the multiple active substances secreted during tick feeding, SPIs have been shown to be directly involved in regulation of inflammation, blood clotting, wound healing, vasoconstriction and the modulation of host defense mechanisms. In light of these activities, several SPIs were examined and were experimentally confirmed to facilitate tick pathogen transmission. In addition, to prevent coagulation of the ingested blood meal within the tick alimentary canal, SPIs are also involved in blood digestion and nutrient extraction from the meal. The presence of SPIs in tick hemocytes and their involvement in tick innate immune defenses have also been demonstrated, as well as their implication in hemolymph coagulation and egg development. Considering the involvement of SPIs in multiple crucial aspects of tick-host-pathogen interactions, as well as in various aspects of the tick parasitic lifestyle, these molecules represent highly suitable and attractive targets for the development of effective tick control strategies. Here we review the current knowledge regarding this class of inhibitors in tick biology and tick-borne pathogen transmission, and their potential as targets for future tick control trials. PMID:28589099

Disruption of Type I Interferon Induction by HIV Infection of T Cells

PubMed Central

Sanchez, David Jesse; Miranda, Daniel; Marsden, Matthew D.; Dizon, Thomas Michael A.; Bontemps, Johnny R.; Davila, Sergio J.; Del Mundo, Lara E.; Ha, Thai; Senaati, Ashkon; Zack, Jerome A.; Cheng, Genhong

2015-01-01

Our main objective of this study was to determine how Human Immunodeficiency Virus (HIV) avoids induction of the antiviral Type I Interferon (IFN) system. To limit viral infection, the innate immune system produces important antiviral cytokines such as the IFN. IFN set up a critical roadblock to virus infection by limiting further replication of a virus. Usually, IFN production is induced by the recognition of viral nucleic acids by innate immune receptors and subsequent downstream signaling. However, the importance of IFN in the defense against viruses has lead most pathogenic viruses to evolve strategies to inhibit host IFN induction or responses allowing for increased pathogenicity and persistence of the virus. While the adaptive immune responses to HIV infection have been extensively studied, less is known about the balance between induction and inhibition of innate immune defenses, including the antiviral IFN response, by HIV infection. Here we show that HIV infection of T cells does not induce significant IFN production even IFN I Interferon production. To explain this paradox, we screened HIV proteins and found that two HIV encoded proteins, Vpu and Nef, strongly antagonize IFN induction, with expression of these proteins leading to loss of expression of the innate immune viral RNA sensing adaptor protein, IPS-1 (IFN-β promoter stimulator-1). We hypothesize that with lower levels of IPS-1 present, infected cells are defective in mounting antiviral responses allowing HIV to replicate without the normal antiviral actions of the host IFN response. Using cell lines as well as primary human derived cells, we show that HIV targeting of IPS-1 is key to limiting IFN induction. These findings describe how HIV infection modulates IFN induction providing insight into the mechanisms by which HIV establishes infection and persistence in a host. PMID:26375588

Disruption of Type I Interferon Induction by HIV Infection of T Cells.

PubMed

Sanchez, David Jesse; Miranda, Daniel; Marsden, Matthew D; Dizon, Thomas Michael A; Bontemps, Johnny R; Davila, Sergio J; Del Mundo, Lara E; Ha, Thai; Senaati, Ashkon; Zack, Jerome A; Cheng, Genhong

2015-01-01

Our main objective of this study was to determine how Human Immunodeficiency Virus (HIV) avoids induction of the antiviral Type I Interferon (IFN) system. To limit viral infection, the innate immune system produces important antiviral cytokines such as the IFN. IFN set up a critical roadblock to virus infection by limiting further replication of a virus. Usually, IFN production is induced by the recognition of viral nucleic acids by innate immune receptors and subsequent downstream signaling. However, the importance of IFN in the defense against viruses has lead most pathogenic viruses to evolve strategies to inhibit host IFN induction or responses allowing for increased pathogenicity and persistence of the virus. While the adaptive immune responses to HIV infection have been extensively studied, less is known about the balance between induction and inhibition of innate immune defenses, including the antiviral IFN response, by HIV infection. Here we show that HIV infection of T cells does not induce significant IFN production even IFN I Interferon production. To explain this paradox, we screened HIV proteins and found that two HIV encoded proteins, Vpu and Nef, strongly antagonize IFN induction, with expression of these proteins leading to loss of expression of the innate immune viral RNA sensing adaptor protein, IPS-1 (IFN-β promoter stimulator-1). We hypothesize that with lower levels of IPS-1 present, infected cells are defective in mounting antiviral responses allowing HIV to replicate without the normal antiviral actions of the host IFN response. Using cell lines as well as primary human derived cells, we show that HIV targeting of IPS-1 is key to limiting IFN induction. These findings describe how HIV infection modulates IFN induction providing insight into the mechanisms by which HIV establishes infection and persistence in a host.

Plant Secondary Metabolites Modulate Insect Behavior-Steps Toward Addiction?

PubMed

Wink, Michael

2018-01-01

Plants produce a diversity of secondary metabolites (PSMs) that serve as defense compounds against herbivores and microorganisms. In addition, some PSMs attract animals for pollination and seed dispersal. In case of pollinating insects, PSMs with colors or terpenoids with fragrant odors attract pollinators in the first place, but when they arrive at a flower, they are rewarded with nectar, so that the pollinators do not feed on flowers. In order to be effective as defense chemicals, PSMs evolved as bioactive substances, that can interfere with a large number of molecular targets in cells, tissues and organs of animals or of microbes. The known functions of PSMs are summarized in this review. A number of PSMs evolved as agonists or antagonists of neuronal signal transduction. Many of these PSMs are alkaloids. Several of them share structural similarities to neurotransmitters. Evidence for neuroactive and psychoactive PSMs in animals will be reviewed. Some of the neuroactive PSMs can cause addiction in humans and other vertrebrates. Why should a defense compound be addictive and thus attract more herbivores? Some insects are food specialists that can feed on plants that are normally toxic to other herbivores. These specialists can tolerate the toxins and many are stored in the insect body as acquired defense chemicals against predators. A special case are pyrrolizidine alkaloids (PAs) that are neurotoxic and mutagenic in vertebrates. PAs are actively sequestered by moths of the family Arctiidae and a few other groups of arthropods. In arctiids, PAs are not only used for defense, but also serve as morphogens for the induction of male coremata and as precursors for male pheromones. Caterpillars even feed on filter paper impregnated with pure PAs (that modulate serotonin receptors in vertebrates and maybe even in insects) and thus show of behavior with has similarities to addiction in vertebrates. Not only PA specialists, but also many monophagous herbivores select their host plants according to chemical cues i.e., PSMs) and crave for plants with a particular PSMs, again a similarity to addiction in vertebrates.

Human Cytomegalovirus Strategies to Maintain and Promote mRNA Translation

PubMed Central

Vincent, Heather A.; Ziehr, Benjamin; Moorman, Nathaniel J.

2016-01-01

mRNA translation requires the ordered assembly of translation initiation factors and ribosomal subunits on a transcript. Host signaling pathways regulate each step in this process to match levels of protein synthesis to environmental cues. In response to infection, cells activate multiple defenses that limit viral protein synthesis, which viruses must counteract to successfully replicate. Human cytomegalovirus (HCMV) inhibits host defenses that limit viral protein expression and manipulates host signaling pathways to promote the expression of both host and viral proteins necessary for virus replication. Here we review key regulatory steps in mRNA translation, and the strategies used by HCMV to maintain protein synthesis in infected cells. PMID:27089357

SELENIUM-DEFICIENCY MODIFIES INFLUENZA INFECTION OF DIFFERENTIATED HUMAN BRONCHIAL EPITHELIAL CELLS

EPA Science Inventory

The nutritional status of the host is important in the defense against invading pathogens. Many studies regarding the effects of host nutritional status on the immune response have demonstrated that suboptimal host nutrition results in impaired host immunity and increased suscept...

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

Processing module operating methods, processing modules, and communications systems

DOEpatents

McCown, Steven Harvey; Derr, Kurt W.; Moore, Troy

2014-09-09

A processing module operating method includes using a processing module physically connected to a wireless communications device, requesting that the wireless communications device retrieve encrypted code from a web site and receiving the encrypted code from the wireless communications device. The wireless communications device is unable to decrypt the encrypted code. The method further includes using the processing module, decrypting the encrypted code, executing the decrypted code, and preventing the wireless communications device from accessing the decrypted code. Another processing module operating method includes using a processing module physically connected to a host device, executing an application within the processing module, allowing the application to exchange user interaction data communicated using a user interface of the host device with the host device, and allowing the application to use the host device as a communications device for exchanging information with a remote device distinct from the host device.

Sequestration and Scavenging of Iron in Infection

PubMed Central

Parrow, Nermi L.; Fleming, Robert E.

2013-01-01

The proliferative capability of many invasive pathogens is limited by the bioavailability of iron. Pathogens have thus developed strategies to obtain iron from their host organisms. In turn, host defense strategies have evolved to sequester iron from invasive pathogens. This review explores the mechanisms employed by bacterial pathogens to gain access to host iron sources, the role of iron in bacterial virulence, and iron-related genes required for the establishment or maintenance of infection. Host defenses to limit iron availability for bacterial growth during the acute-phase response and the consequences of iron overload conditions on susceptibility to bacterial infection are also examined. The evidence summarized herein demonstrates the importance of iron bioavailability in influencing the risk of infection and the ability of the host to clear the pathogen. PMID:23836822

The Orphan Nuclear Receptor TLX Is an Enhancer of STAT1-Mediated Transcription and Immunity to Toxoplasma gondii.

PubMed

Beiting, Daniel P; Hidano, Shinya; Baggs, Julie E; Geskes, Jeanne M; Fang, Qun; Wherry, E John; Hunter, Christopher A; Roos, David S; Cherry, Sara

2015-07-01

The protozoan parasite, Toxoplasma, like many intracellular pathogens, suppresses interferon gamma (IFN-γ)-induced signal transducer and activator of transcription 1 (STAT1) activity. We exploited this well-defined host-pathogen interaction as the basis for a high-throughput screen, identifying nine transcription factors that enhance STAT1 function in the nucleus, including the orphan nuclear hormone receptor TLX. Expression profiling revealed that upon IFN-γ treatment TLX enhances the output of a subset of IFN-γ target genes, which we found is dependent on TLX binding at those loci. Moreover, infection of TLX deficient mice with the intracellular parasite Toxoplasma results in impaired production of the STAT1-dependent cytokine interleukin-12 by dendritic cells and increased parasite burden in the brain during chronic infection. These results demonstrate a previously unrecognized role for this orphan nuclear hormone receptor in regulating STAT1 signaling and host defense and reveal that STAT1 activity can be modulated in a context-specific manner by such "modifiers."

Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I.

PubMed

Gack, Michaela Ulrike; Albrecht, Randy Allen; Urano, Tomohiko; Inn, Kyung-Soo; Huang, I-Chueh; Carnero, Elena; Farzan, Michael; Inoue, Satoshi; Jung, Jae Ung; García-Sastre, Adolfo

2009-05-08

The ubiquitin ligase TRIM25 mediates Lysine 63-linked ubiquitination of the N-terminal CARD domains of the viral RNA sensor RIG-I to facilitate type I interferon (IFN) production and antiviral immunity. Here, we report that the influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD domain ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in blocking TRIM25-mediated antiviral IFN response and loses virulence in mice. Our findings reveal a mechanism by which influenza virus inhibits host IFN response and also emphasize the vital role of TRIM25 in modulating antiviral defenses.

PARP12 suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins.

PubMed

Li, Lili; Zhao, Hui; Liu, Ping; Li, Chunfeng; Quanquin, Natalie; Ji, Xue; Sun, Nina; Du, Peishuang; Qin, Cheng-Feng; Lu, Ning; Cheng, Genhong

2018-06-19

Zika virus infection stimulates a type I interferon (IFN) response in host cells, which suppresses viral replication. Type I IFNs exert antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). To screen for antiviral ISGs that restricted Zika virus replication, we individually knocked out 21 ISGs in A549 lung cancer cells and identified PARP12 as a strong inhibitor of Zika virus replication. Our findings suggest that PARP12 mediated the ADP-ribosylation of NS1 and NS3, nonstructural viral proteins that are involved in viral replication and modulating host defense responses. This modification of NS1 and NS3 triggered their proteasome-mediated degradation. These data increase our understanding of the antiviral activity of PARP12 and suggest a molecular basis for the potential development of therapeutics against Zika virus. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

Powell, Joshua D.; Chen, Qiang; Mason, Hugh S.

Abstract Key message nta-miR-398 is significantly up-regulated while nta-miR-428d is significantly down-regulated in tobacco after agroinfiltration AbstractMicroRNAs are a class of non-coding regulatory RNAs that can modulate development as well as alter innate antiviral defenses in plants. In this study we explored host changes at the microRNA level within tobacco (Nicotiana benthamiana) after expression of a recombinant anti-Ebola GP1 antibody through Agrobacterium tumefaciens agroinfiltration delivery. A multiplex nanoparticle-based cytometry assay tracked the host expression changes of 53 tobacco microRNAs. Our results revealed that the most abundant microRNAs in actively growing leaves corresponded to nanoparticle probes specific to nta-mir-6149 and nta-miR-168b.more » After agroinfiltration, probes targeting nta-mir-398 and nta-mir-482d were significantly altered in their respective expression levels and were further verified through RT-qPCR analysis. To our knowledge this study is the first to profile microRNA expression in tobacco after agroinfiltration using a multiplex nanoparticle approach.« less

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...

Gut microbiota imbalance and colorectal cancer

PubMed Central

Gagnière, Johan; Raisch, Jennifer; Veziant, Julie; Barnich, Nicolas; Bonnet, Richard; Buc, Emmanuel; Bringer, Marie-Agnès; Pezet, Denis; Bonnet, Mathilde

2016-01-01

The gut microbiota acts as a real organ. The symbiotic interactions between resident micro-organisms and the digestive tract highly contribute to maintain the gut homeostasis. However, alterations to the microbiome caused by environmental changes (e.g., infection, diet and/or lifestyle) can disturb this symbiotic relationship and promote disease, such as inflammatory bowel diseases and cancer. Colorectal cancer is a complex association of tumoral cells, non-neoplastic cells and a large amount of micro-organisms, and the involvement of the microbiota in colorectal carcinogenesis is becoming increasingly clear. Indeed, many changes in the bacterial composition of the gut microbiota have been reported in colorectal cancer, suggesting a major role of dysbiosis in colorectal carcinogenesis. Some bacterial species have been identified and suspected to play a role in colorectal carcinogenesis, such as Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis, Enterococcus faecalis, Clostridium septicum, Fusobacterium spp. and Escherichia coli. The potential pro-carcinogenic effects of these bacteria are now better understood. In this review, we discuss the possible links between the bacterial microbiota and colorectal carcinogenesis, focusing on dysbiosis and the potential pro-carcinogenic properties of bacteria, such as genotoxicity and other virulence factors, inflammation, host defenses modulation, bacterial-derived metabolism, oxidative stress and anti-oxidative defenses modulation. We lastly describe how bacterial microbiota modifications could represent novel prognosis markers and/or targets for innovative therapeutic strategies. PMID:26811603

Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats.

PubMed

Luck, Christian; DeMarco, Vincent G; Mahmood, Abuzar; Gavini, Madhavi P; Pulakat, Lakshmi

2017-01-01

Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750  μ g/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters ( E / E ', E '/ A ', E / Vp ) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFN γ , and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes.

Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

PubMed Central

Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

2017-01-01

Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes. PMID:28408970

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.

Expression of an Engineered Heterologous Antimicrobial Peptide in Potato Alters Plant Development and Mitigates Normal Abiotic and Biotic Responses

PubMed Central

Goyal, Ravinder K.; Hancock, Robert E. W.; Mattoo, Autar K.; Misra, Santosh

2013-01-01

Antimicrobial cationic peptides (AMPs) are ubiquitous small proteins used by living cells to defend against a wide spectrum of pathogens. Their amphipathic property helps their interaction with negatively charged cellular membrane of the pathogen causing cell lysis and death. AMPs also modulate signaling pathway(s) and cellular processes in animal models; however, little is known of cellular processes other than the pathogen-lysis phenomenon modulated by AMPs in plants. An engineered heterologous AMP, msrA3, expressed in potato was previously shown to cause resistance of the transgenic plants against selected fungal and bacterial pathogens. These lines together with the wild type were studied for growth habits, and for inducible defense responses during challenge with biotic (necrotroph Fusarium solani) and abiotic stressors (dark-induced senescence, wounding and temperature stress). msrA3-expression not only conferred protection against F. solani but also delayed development of floral buds and prolonged vegetative phase. Analysis of select gene transcript profiles showed that the transgenic potato plants were suppressed in the hypersensitive (HR) and reactive oxygen species (ROS) responses to both biotic and abiotic stressors. Also, the transgenic leaves accumulated lesser amounts of the defense hormone jasmonic acid upon wounding with only a slight change in salicylic acid as compared to the wild type. Thus, normal host defense responses to the pathogen and abiotic stressors were mitigated by msrA3 expression suggesting MSRA3 regulates a common step(s) of these response pathways. The stemming of the pathogen growth and mitigating stress response pathways likely contributes to resource reallocation for higher tuber yield. PMID:24147012

Mobile Genetic Elements and Evolution of CRISPR-Cas Systems: All the Way There and Back

PubMed Central

Makarova, Kira S.

2017-01-01

Abstract The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-CRISPR-associated proteins (Cas) systems of bacterial and archaeal adaptive immunity show multifaceted evolutionary relationships with at least five classes of mobile genetic elements (MGE). First, the adaptation module of CRISPR-Cas that is responsible for the formation of the immune memory apparently evolved from a Casposon, a self-synthesizing transposon that employs the Cas1 protein as the integrase and might have brought additional cas genes to the emerging immunity loci. Second, a large subset of type III CRISPR-Cas systems recruited a reverse transcriptase from a Group II intron, providing for spacer acquisition from RNA. Third, effector nucleases of Class 2 CRISPR-Cas systems that are responsible for the recognition and cleavage of the target DNA were derived from transposon-encoded TnpB nucleases, most likely, on several independent occasions. Fourth, accessory nucleases in some variants of types I and III toxin and type VI effectors RNases appear to be ultimately derived from toxin nucleases of microbial toxin–antitoxin modules. Fifth, the opposite direction of evolution is manifested in the recruitment of CRISPR-Cas systems by a distinct family of Tn7-like transposons that probably exploit the capacity of CRISPR-Cas to recognize unique DNA sites to facilitate transposition as well as by bacteriophages that employ them to cope with host defense. Additionally, individual Cas proteins, such as the Cas4 nuclease, were recruited by bacteriophages and transposons. The two-sided evolutionary connection between CRISPR-Cas and MGE fits the “guns for hire” paradigm whereby homologous enzymatic machineries, in particular nucleases, are shuttled between MGE and defense systems and are used alternately as means of offense or defense. PMID:28985291

JMJ27, an Arabidopsis H3K9 histone demethylase, modulates defense against Pseudomonas syringae and flowering time.

PubMed

Dutta, Aditya; Choudhary, Pratibha; Caruana, Julie; Raina, Ramesh

2017-09-01

Histone methylation is known to dynamically regulate diverse developmental and physiological processes. Histone methyl marks are written by methyltransferases and erased by demethylases, and result in modification of chromatin structure to repress or activate transcription. However, little is known about how histone methylation may regulate defense mechanisms and flowering time in plants. Here we report characterization of JmjC DOMAIN-CONTAINING PROTEIN 27 (JMJ27), an Arabidopsis JHDM2 (JmjC domain-containing histone demethylase 2) family protein, which modulates defense against pathogens and flowering time. JMJ27 is a nuclear protein containing a zinc-finger motif and a catalytic JmjC domain with conserved Fe(II) and α-ketoglutarate binding sites, and displays H3K9me1/2 demethylase activity both in vitro and in vivo. JMJ27 is induced in response to virulent Pseudomonas syringae pathogens and is required for resistance against these pathogens. JMJ27 is a negative modulator of WRKY25 (a repressor of defense) and a positive modulator of several pathogenesis-related (PR) proteins. Additionally, loss of JMJ27 function leads to early flowering. JMJ27 negatively modulates the major flowering regulator CONSTANS (CO) and positively modulates FLOWERING LOCUS C (FLC). Taken together, our results indicate that JMJ27 functions as a histone demethylase to modulate both physiological (defense) and developmental (flowering time) processes in Arabidopsis. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Apoplastic interactions between plants and plant root intruders.

PubMed

Mitsumasu, Kanako; Seto, Yoshiya; Yoshida, Satoko

2015-01-01

Numerous pathogenic or parasitic organisms attack plant roots to obtain nutrients, and the apoplast including the plant cell wall is where the plant cell meets such organisms. Root parasitic angiosperms and nematodes are two distinct types of plant root parasites but share some common features in their strategies for breaking into plant roots. Striga and Orobanche are obligate root parasitic angiosperms that cause devastating agricultural problems worldwide. Parasitic plants form an invasion organ called a haustorium, where plant cell wall degrading enzymes (PCWDEs) are highly expressed. Plant-parasitic nematodes are another type of agriculturally important plant root parasite. These nematodes breach the plant cell walls by protruding a sclerotized stylet from which PCWDEs are secreted. Responding to such parasitic invasion, host plants activate their own defense responses against parasites. Endoparasitic nematodes secrete apoplastic effectors to modulate host immune responses and to facilitate the formation of a feeding site. Apoplastic communication between hosts and parasitic plants also contributes to their interaction. Parasitic plant germination stimulants, strigolactones, are recently identified apoplastic signals that are transmitted over long distances from biosynthetic sites to functioning sites. Here, we discuss recent advances in understanding the importance of apoplastic signals and cell walls for plant-parasite interactions.

Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain.

PubMed

Keriel, Anne; Botella, Eric; Estrach, Soline; Bragagnolo, Gabriel; Vergunst, Annette C; Feral, Chloe C; O'Callaghan, David

2015-06-01

Brucella are intracellular bacterial pathogens that use a type IV secretion system (T4SS) to escape host defenses and create a niche in which they can multiply. Although the importance of Brucella T4SS is clear, little is known about its interactions with host cell structures. In this study, we identified the eukaryotic protein CD98hc as a partner for Brucella T4SS subunit VirB2. This transmembrane glycoprotein is involved in amino acid transport, modulation of integrin signaling, and cell-to-cell fusion. Knockdown of CD98hc expression in HeLa cells demonstrated that it is essential for Brucella infection. Using knockout dermal fibroblasts, we confirmed its role for Brucella but found that it is not required for Salmonella infection. CD98hc transiently accumulates around the bacteria during the early phases of infection and is required for both optimal bacterial uptake and intracellular multiplication of Brucella. These results provide new insights into the complex interplay between Brucella and its host. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Apoplastic interactions between plants and plant root intruders

PubMed Central

Mitsumasu, Kanako; Seto, Yoshiya; Yoshida, Satoko

2015-01-01

Numerous pathogenic or parasitic organisms attack plant roots to obtain nutrients, and the apoplast including the plant cell wall is where the plant cell meets such organisms. Root parasitic angiosperms and nematodes are two distinct types of plant root parasites but share some common features in their strategies for breaking into plant roots. Striga and Orobanche are obligate root parasitic angiosperms that cause devastating agricultural problems worldwide. Parasitic plants form an invasion organ called a haustorium, where plant cell wall degrading enzymes (PCWDEs) are highly expressed. Plant-parasitic nematodes are another type of agriculturally important plant root parasite. These nematodes breach the plant cell walls by protruding a sclerotized stylet from which PCWDEs are secreted. Responding to such parasitic invasion, host plants activate their own defense responses against parasites. Endoparasitic nematodes secrete apoplastic effectors to modulate host immune responses and to facilitate the formation of a feeding site. Apoplastic communication between hosts and parasitic plants also contributes to their interaction. Parasitic plant germination stimulants, strigolactones, are recently identified apoplastic signals that are transmitted over long distances from biosynthetic sites to functioning sites. Here, we discuss recent advances in understanding the importance of apoplastic signals and cell walls for plant–parasite interactions. PMID:26322059

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.

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

Alan M Kaplan

This grant will be used to augment the equipment infrastructure and core support at the University of Kentucky and the University of Alabama particularly in the areas of genomics/informatics, molecular analysis and cell separation. In addition, we will promote collaborative research interactions through scientific workshops and exchange of scientists, as well as joint exploration of the role of immune receptors as targets in autoimmunity and host defense, innate and adaptive immune responses, and mucosal immunity in host defense.

Department of Defense Chemical and Biological Defense Program. FY2002-2004 Performance Plan. Volume 2

DTIC Science & Technology

2003-04-01

agents identified by in vitro assays in mouse models. Studied the effect of immunomodulators on the host response to Burkholderia mallei ( glanders ...identifiers) of various isolates of the organism responsible for plague (Y. pestis), glanders (B. mallei ), and anthrax (B. anthracis). Evaluate...suitable animal models. Study the effect of immunomodulators on the host response to B. mallei and Y. pestis candidate vaccines; identify those

ROS open roads to roundworm infection.

PubMed

Feng, Baomin; Shan, Libo

2014-04-08

The rapid production of reactive oxygen species (ROS) upon pathogen attack is generally considered a defense mechanism for microbial killing and an initiation of host defense responses in plants and animals. In this issue, Siddique et al. show that nicotinamide adenine dinucleotide phosphate oxidase-derived ROS function as a pathogenicity factor to promote the roundworm nematode infection in Arabidopsis thaliana, revealing the complex action of ROS in host-pathogen interactions.

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.

Analysis of Globodera rostochiensis effectors reveals conserved functions of SPRYSEC proteins in suppressing and eliciting plant immune responses.

PubMed

Ali, Shawkat; Magne, Maxime; Chen, Shiyan; Obradovic, Natasa; Jamshaid, Lubna; Wang, Xiaohong; Bélair, Guy; Moffett, Peter

2015-01-01

Potato cyst nematodes (PCNs), including Globodera rostochiensis (Woll.), are important pests of potato. Plant parasitic nematodes produce multiple effector proteins, secreted from their stylets, to successfully infect their hosts. These include proteins delivered to the apoplast and to the host cytoplasm. A number of effectors from G. rostochiensis predicted to be delivered to the host cytoplasm have been identified, including several belonging to the secreted SPRY domain (SPRYSEC) family. SPRYSEC proteins are unique to members of the genus Globodera and have been implicated in both the induction and the repression of host defense responses. We have tested the properties of six different G. rostochiensis SPRYSEC proteins by expressing them in Nicotiana benthamiana and N. tabacum. We have found that all SPRYSEC proteins tested are able to suppress defense responses induced by NB-LRR proteins as well as cell death induced by elicitors, suggesting that defense repression is a common characteristic of members of this effector protein family. At the same time, GrSPRYSEC-15 elicited a defense responses in N. tabacum, which was found to be resistant to a virus expressing GrSPRYSEC-15. These results suggest that SPRYSEC proteins may possess characteristics that allow them to be recognized by the plant immune system.

Regulation of mitochondrial biogenesis and its intersection with inflammatory responses.

PubMed

Cherry, Anne D; Piantadosi, Claude A

2015-04-20

Mitochondria play a vital role in cellular homeostasis and are susceptible to damage from inflammatory mediators released by the host defense. Cellular recovery depends, in part, on mitochondrial quality control programs, including mitochondrial biogenesis. Early-phase inflammatory mediator proteins interact with PRRs to activate NF-κB-, MAPK-, and PKB/Akt-dependent pathways, resulting in increased expression or activity of coactivators and transcription factors (e.g., PGC-1α, NRF-1, NRF-2, and Nfe2l2) that regulate mitochondrial biogenesis. Inflammatory upregulation of NOS2-induced NO causes mitochondrial dysfunction, but NO is also a signaling molecule upregulating mitochondrial biogenesis via PGC-1α, participating in Nfe2l2-mediated antioxidant gene expression and modulating inflammation. NO and reactive oxygen species generated by the host inflammatory response induce the redox-sensitive HO-1/CO system, causing simultaneous induction of mitochondrial biogenesis and antioxidant gene expression. Recent evidence suggests that mitochondrial biogenesis and mitophagy are coupled through redox pathways; for instance, parkin, which regulates mitophagy in chronic inflammation, may also modulate mitochondrial biogenesis and is upregulated through NF-κB. Further research on parkin in acute inflammation is ongoing. This highlights certain common features of the host response to acute and chronic inflammation, but caution is warranted in extrapolating findings across inflammatory conditions. Inflammatory mitochondrial dysfunction and oxidative stress initiate further inflammatory responses through DAMP/PRR interactions and by inflammasome activation, stimulating mitophagy. A deeper understanding of mitochondrial quality control programs' impact on intracellular inflammatory signaling will improve our approach to the restoration of mitochondrial homeostasis in the resolution of acute inflammation.

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.

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.

MAIT cells: new guardians of the liver.

PubMed

Kurioka, Ayako; Walker, Lucy J; Klenerman, Paul; Willberg, Christian B

2016-08-01

The liver is an important immunological organ that remains sterile and tolerogenic in homeostasis, despite continual exposure to non-self food and microbial-derived products from the gut. However, where intestinal mucosal defenses are breached or in the presence of a systemic infection, the liver acts as a second 'firewall', because of its enrichment with innate effector cells able to rapidly respond to infections or tissue dysregulation. One of the largest populations of T cells within the human liver are mucosal-associated invariant T (MAIT) cells, a novel innate-like T-cell population that can recognize a highly conserved antigen derived from the microbial riboflavin synthesis pathway. MAIT cells are emerging as significant players in the human immune system, associated with an increasing number of clinical diseases of bacterial, viral, autoimmune and cancerous origin. As reviewed here, we are only beginning to investigate the potential role of this dominant T-cell subset in the liver, but the reactivity of MAIT cells to both inflammatory cytokines and riboflavin derivatives suggests that MAIT cells may have an important role in first line of defense as part of the liver firewall. As such, MAIT cells are promising targets for modulating the host defense and inflammation in both acute and chronic liver diseases.

MAIT cells: new guardians of the liver

PubMed Central

Kurioka, Ayako; Walker, Lucy J; Klenerman, Paul; Willberg, Christian B

2016-01-01

The liver is an important immunological organ that remains sterile and tolerogenic in homeostasis, despite continual exposure to non-self food and microbial-derived products from the gut. However, where intestinal mucosal defenses are breached or in the presence of a systemic infection, the liver acts as a second 'firewall', because of its enrichment with innate effector cells able to rapidly respond to infections or tissue dysregulation. One of the largest populations of T cells within the human liver are mucosal-associated invariant T (MAIT) cells, a novel innate-like T-cell population that can recognize a highly conserved antigen derived from the microbial riboflavin synthesis pathway. MAIT cells are emerging as significant players in the human immune system, associated with an increasing number of clinical diseases of bacterial, viral, autoimmune and cancerous origin. As reviewed here, we are only beginning to investigate the potential role of this dominant T-cell subset in the liver, but the reactivity of MAIT cells to both inflammatory cytokines and riboflavin derivatives suggests that MAIT cells may have an important role in first line of defense as part of the liver firewall. As such, MAIT cells are promising targets for modulating the host defense and inflammation in both acute and chronic liver diseases. PMID:27588203

Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium.

PubMed

Dusio, Giuseppina F; Cardani, Diego; Zanobbio, Laura; Mantovani, Martina; Luchini, Patrizia; Battini, Lorenzo; Galli, Valentina; Diana, Angela; Balsari, Andrea; Rumio, Cristiano

2011-07-01

The innate immune system is present throughout the female reproductive tract and functions in synchrony with the adaptive immune system to provide protection in a way that enhances the chances for fetal survival, while protecting against potential pathogens. Recent data show that activation of Toll-like receptor (TLR)2 and 4 by low-molecular weight hyaluronic acid (LMW-HA) in the epidermis induces secretion of the antimicrobial peptide β-defensin 2. In the present work, we show that LMW-HA induces vaginal epithelial cells to release different antimicrobial peptides, via activation of TLR2 and TLR4. Further, we found that LMW-HA favors repair of vaginal epithelial injury, involving TLR2 and TLR4, and independently from its classical receptor CD44. This wound-healing activity of LMW-HA is dependent from an Akt/phosphatidylinositol 3 kinase pathway. Therefore, these findings suggest that the vaginal epithelium is more than a simple physical barrier to protect against invading pathogens: on the contrary, this surface acts as efficient player of innate host defense, which may modulate its antimicrobial properties and injury restitution activity, following LMW-HA stimulation; this activity may furnish an additional protective activity to this body compartment, highly and constantly exposed to microbiota, ameliorating the self-defense of the vaginal epithelium in both basal and pathological conditions.

Crosstalk among Jasmonate, Salicylate and Ethylene Signaling Pathways in Plant Disease and Immune Responses.

PubMed

Yang, You-Xin; Ahammed, Golam J; Wu, Caijun; Fan, Shu-ying; Zhou, Yan-Hong

2015-01-01

Phytohormone crosstalk is crucial for plant defenses against pathogens and insects in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) play key roles. These low molecular mass signals critically trigger and modulate plant resistance against biotrophic as well as necrotrophic pathogens through a complex signaling network that even involves participation of other hormones. Crosstalk among SA, JA and ET is mediated by different molecular players, considered as integral part of these crosscommunicating signal transduction pathways. Recent progress has revealed that the positive versus negative interactions among those pathways ultimately enable a plant to fine-tune its defense against specific aggressors. On the other hand, pathogens have evolved strategies to manipulate the signaling network to their favour in order to intensify virulence on host plant. Here we review recent advances and current knowledge on the role of classical primary defense hormones SA, JA and ET as well as their synergistic and antagonistic interaction in plant disease and immune responses. Crosstalk with other hormones such as abscisic acid, auxin, brassinosteroids, cytokinins and melatonin is also discussed mainly in plant disease resistance. In addition to our keen focus on hormonal crosstalk, this review also highlights potential implication of positive and negative regulatory interactions for developing an efficient disease management strategy through manipulation of hormone signaling in plant.

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...

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...

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 transmitted via the dietary specialist aphid, but these effects varied substantially among predators-in both the magnitude and direction-when transmitted via the dietary generalist aphid. Accordingly, the cascading effect of plant defense on predators was stronger in magnitude and more consistent among predator taxa when transmitted by the specialist than generalist herbivore. Overall, these findings support a central role of herbivore diet breadth in mediating both the strength and contingency of tri-trophic interactions.

The Contribution of the Airway Epithelial Cell to Host Defense.

PubMed

Stanke, Frauke

2015-01-01

In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate CFTR-mediated chloride and bicarbonate transport has been recognized early as a means to regulate the thickness of the epithelial lining fluid and recently as a means to regulate the pH, thereby determining critically whether or not host defense proteins such as mucins are able to fold appropriately. This review describes how the epithelial cell senses the presence of pathogens and inflammatory conditions, which, in turn, facilitates the activation of CFTR and thus directly promotes pathogens clearance and innate immune defense on the surface of the epithelial cell. This paper summarizes functional data that describes the effect of cytokines, chemokines, infectious agents, and inflammatory conditions on the ion transport properties of the epithelial cell and relates these key properties to the molecular pathology of cystic fibrosis. Recent findings on the role of cystic fibrosis modifier genes that underscore the role of the epithelial ion transport in host defense and inflammation are discussed.

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.

The Development of Antimicrobial α-AApeptides that Suppress Pro-inflammatory Immune Responses

PubMed Central

Padhee, Shruti; Smith, Christina; Wu, Haifan; Li, Yaqiong; Manoj, Namitha; Qiao, Qiao; Khan, Zoya; Cao, Chuanhai

2014-01-01

Herein we describe the development of a new class of antimicrobial and anti-infective peptidomimetics – cyclic lipo-α-AApeptides. They have potent and broad-spectrum antibacterial activity against a range of clinically relevant pathogens, including both multidrug-resistant Gram-positive and Gram-negative bacteria. Fluorescence microscopy suggests that cyclic lipo-α-AApeptides kill bacteria by disrupting bacterial membranes, possibly through a mechanism similar to that of cationic host defense peptides (HDPs). Furthermore, the cyclic lipo-α-AApeptide can mimic cationic host-defense peptides by antagonizing Toll-Like Receptor 4 (TLR4) signaling responses and suppressing pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). Our results suggest that by mimicking host-defense peptides (HDPs), cyclic lipo-α-AApeptides may emerge to be a new class of antibiotic agents through direct bacteria killing, as well as novel anti-infective agents through immunomodulation. PMID:24677440

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

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.

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.

Regulation of Cytokine Production by the Unfolded Protein Response; Implications for Infection and Autoimmunity

PubMed Central

Smith, Judith A.

2018-01-01

Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation. The UPR influences cytokine production on multiple levels, from stimulation of pattern recognition receptors, to modulation of inflammatory signaling pathways, and the regulation of cytokine transcription factors. This review will focus on the mechanisms underlying cytokine regulation by the UPR, and the repercussions of this relationship for infection and autoimmune/autoinflammatory diseases. Interrogation of viral and bacterial infections has revealed increasing numbers of examples where pathogens induce or modulate the UPR and implicated UPR-modulated cytokines in host response. The flip side of this coin, the UPR/ER stress responses have been increasingly recognized in a variety of autoimmune and inflammatory diseases. Examples include monogenic disorders of ER function, diseases linked to misfolding protein (HLA-B27 and spondyloarthritis), diseases directly implicating UPR and autophagy genes (inflammatory bowel disease), and autoimmune diseases targeting highly secretory cells (e.g., diabetes). Given the burgeoning interest in pharmacologically targeting the UPR, greater discernment is needed regarding how the UPR regulates cytokine production during specific infections and autoimmune processes, and the relative place of this interaction in pathogenesis. PMID:29556237

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

Human rhinovirus-induced ISG15 selectively modulates epithelial antiviral immunity

PubMed Central

Zaheer, R S; Wiehler, S; Hudy, M H; Traves, S L; Pelikan, J B; Leigh, R; Proud, D

2014-01-01

Human rhinovirus (HRV) infections trigger exacerbations of lower airway diseases. HRV infects human airway epithelial cells and induces proinflammatory and antiviral molecules that regulate the response to HRV infection. Interferon (IFN)-stimulated gene of 15 kDa (ISG15) has been shown to regulate other viruses. We now show that HRV-16 infection induces both intracellular epithelial ISG15 expression and ISG15 secretion in vitro. Moreover, ISG15 protein levels increased in nasal secretions of subjects with symptomatic HRV infections. HRV-16-induced ISG15 expression is transcriptionally regulated via an IFN regulatory factor pathway. ISG15 does not directly alter HRV replication but does modulate immune signaling via the viral sensor protein RIG-I to impact production of CXCL10, which has been linked to innate immunity to viruses. Extracellular ISG15 also alters CXCL10 production. We conclude that ISG15 has a complex role in host defense against HRV infection, and that additional studies are needed to clarify the role of this molecule. PMID:24448099

Host modulation therapy: An indispensable part of perioceutics

PubMed Central

Gulati, Minkle; Anand, Vishal; Govila, Vivek; Jain, Nikil

2014-01-01

Traditionally, only antimicrobials have been used as the chemotherapeutic modality for the treatment of periodontitis. Though bacteria are the primary etiologic factors of periodontal diseases, yet the extent and severity of tissue destruction seen in periodontitis is determined by the host immuno-inflammatory response to these bacteria. This increasing awareness and knowledge of the host-microbial interaction in periodontal pathogenesis has presented the opportunity for exploring new therapeutic strategies for periodontitis by means of targeting host response via host-modulating agents. This has lead to the emergence of the field of “Perioceutics” i.e. the use of parmacotherapeutic agents including antimicrobial therapy as well as host modulatory therapy for the management of periodontitis. These host-modulating agents used as an adjunct tip the balance between periodontal health and disease progression in the direction of a healing response. In this article the host-modulating role of various systemically and locally delivered perioceutic agents will be reviewed. PMID:25024538

Learning from the Messengers: Innate Sensing of Viruses and Cytokine Regulation of Immunity—Clues for Treatments and Vaccines

PubMed Central

Melchjorsen, Jesper

2013-01-01

Virus infections are a major global public health concern, and only via substantial knowledge of virus pathogenesis and antiviral immune responses can we develop and improve medical treatments, and preventive and therapeutic vaccines. Innate immunity and the shaping of efficient early immune responses are essential for control of viral infections. In order to trigger an efficient antiviral defense, the host senses the invading microbe via pattern recognition receptors (PRRs), recognizing distinct conserved pathogen-associated molecular patterns (PAMPs). The innate sensing of the invading virus results in intracellular signal transduction and subsequent production of interferons (IFNs) and proinflammatory cytokines. Cytokines, including IFNs and chemokines, are vital molecules of antiviral defense regulating cell activation, differentiation of cells, and, not least, exerting direct antiviral effects. Cytokines shape and modulate the immune response and IFNs are principle antiviral mediators initiating antiviral response through induction of antiviral proteins. In the present review, I describe and discuss the current knowledge on early virus–host interactions, focusing on early recognition of virus infection and the resulting expression of type I and type III IFNs, proinflammatory cytokines, and intracellular antiviral mediators. In addition, the review elucidates how targeted stimulation of innate sensors, such as toll-like receptors (TLRs) and intracellular RNA and DNA sensors, may be used therapeutically. Moreover, I present and discuss data showing how current antimicrobial therapies, including antibiotics and antiviral medication, may interfere with, or improve, immune response. PMID:23435233

Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization

PubMed Central

Hyre, Amanda N.; Kavanagh, Kylie; Kock, Nancy D.; Donati, George L.

2016-01-01

ABSTRACT Urinary tract infection (UTI) is a major global infectious disease affecting millions of people annually. Human urinary copper (Cu) content is elevated during UTI caused by uropathogenic Escherichia coli (UPEC). UPEC upregulates the expression of Cu efflux genes during clinical UTI in patients as an adaptive response to host-derived Cu. Whether Cu is mobilized to urine as a host response to UTI and its role in protection against UTI remain unresolved. To address these questions, we tested the hypothesis that Cu is a host effector mobilized to urine during UTI to limit bacterial growth. Our results reveal that Cu is mobilized to urine during UTI caused by the major uropathogens Proteus mirabilis and Klebsiella pneumoniae, in addition to UPEC, in humans. Ceruloplasmin, a Cu-containing ferroxidase, is found at higher levels in UTI urine than in healthy control urine and serves as the molecular source of urinary Cu during UTI. Our results demonstrate that ceruloplasmin decreases the bioavailability of iron in urine by a transferrin-dependent mechanism. Experimental UTI with UPEC in nonhuman primates recapitulates the increased urinary Cu content observed during clinical UTI. Furthermore, Cu-deficient mice are highly colonized by UPEC, indicating that Cu is involved in the limiting of bacterial growth within the urinary tract. Collectively, our results indicate that Cu is a host effector that is involved in protection against pathogen colonization of the urinary tract. Because urinary Cu levels are amenable to modulation, augmentation of the Cu-based host defense against UTI represents a novel approach to limiting bacterial colonization during UTI. PMID:28031261

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.

Recent Advances in Aptamers Targeting Immune System.

PubMed

Hu, Piao-Ping

2017-02-01

The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

Reciprocal Interactions of the Intestinal Microbiota and Immune System

PubMed Central

Maynard, Craig L.; Elson, Charles O.; Hatton, Robin D.; Weaver, Casey T.

2013-01-01

Preface Emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defense. These same attributes carry risk for immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how it integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks in order to treat and prevent disease. PMID:22972296

Human Common Salivary Protein 1 (CSP-1) Promotes Binding of Streptococcus mutans to Experimental Salivary Pellicle and Glucans Formed on Hydroxyapatite Surface

PubMed Central

Ambatipudi, Kiran S.; Hagen, Fred K.; Delahunty, Claire M.; Han, Xuemei; Shafi, Rubina; Hryhorenko, Jennifer; Gregoire, Stacy; Marquis, Robert E.; Melvin, James E.; Koo, Hyun; Yates, John R.

2010-01-01

Summary The saliva proteome includes host defense factors and specific bacterial-binding proteins that modulate microbial growth and colonization of tooth surface in the oral cavity. A multidimensional mass spectrometry approach identified the major host-derived salivary proteins which interacted with Streptococcus mutans (strain UA159), the primary microorganism associated with the pathogenesis of dental caries. Two abundant host proteins were found to tightly bind to S. mutans cells, common salivary protein-1 (CSP-1) and deleted in malignant brain tumor 1 (DMBT1, also known as salivary agglutinin or gp340). In contrast to gp340, limited functional information is available on CSP-1. The sequence of CSP-1 shares 38.1% similarity with rat CSP-1. Recombinant CSP-1 (rCSP-1) protein did not cause aggregation of S. mutans cells and was devoid of any significant biocidal activity (2.5 to 10 μg/ml). However, S. mutans cells exposed to rCSP-1 (10 μg/ml) in saliva displayed enhanced adherence to experimental salivary pellicle and to glucans in the pellicle formed on hydroxyapatite surfaces. Thus, our data demonstrate that the host salivary protein CSP-1 binds to S. mutans cells and may influence the initial colonization of this pathogenic bacterium onto tooth surface. PMID:20858015

Genome-Wide RNAi Screen Identifies Broadly-Acting Host Factors That Inhibit Arbovirus Infection

PubMed Central

Yasunaga, Ari; Hanna, Sheri L.; Li, Jianqing; Cho, Hyelim; Rose, Patrick P.; Spiridigliozzi, Anna; Gold, Beth; Diamond, Michael S.; Cherry, Sara

2014-01-01

Vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. In particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type I interferon response in vertebrates and the RNA interference (RNAi) pathway in insects. However, it is likely that additional cell-intrinsic mechanisms exist to limit these viruses. Since insects rely on innate immune mechanisms to inhibit virus infections, we used Drosophila as a model insect to identify cellular factors that restrict West Nile virus (WNV), a flavivirus with a broad and expanding geographical host range. Our genome-wide RNAi screen identified 50 genes that inhibited WNV infection. Further screening revealed that 17 of these genes were antiviral against additional flaviviruses, and seven of these were antiviral against other vector-borne viruses, expanding our knowledge of invertebrate cell-intrinsic immunity. Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts. PMID:24550726

[Modulating Effect of Extracellular HSP70 on Generation of Reactive Oxigen Species in Populations of Phagocytes].

PubMed

Troyanova, N I; Shevchenko, M A; Boyko, A A; Mirzoyev, R R; Pertseva, M A; Kovalenko, E I; Sapozhnikov, A M

2015-01-01

Reactive oxygen species (ROS) produced by phagocytic cells of the innate immune system play an important role in the first line of defense protecting the host from pathogens. The NADPH oxidase multi-subunit complex is the main source of ROS in all types of the phagocytes. Formation of the membrane-associated enzyme complex and its activity are dependent on many different factors controlling both intensification and suppression of the ROS production rate. However, the evidences are emerging in recent years indicating existence of poorly studied mechanisms of restriction of ROS generation level in phagocytes directed at protection of host tissues in the sites of inflammation from destruction caused by the oxygen free radicals. Our previous data and results of other authors demonstrate that a mechanism of the limitation of ROS production by phagocytes may by connected with immunomodulating activity of extracellular pool. of HSP70. In the present work, we used inhibitors of NADPH oxidase and in vitro cultures of different phagocytes to study a possible relationship between down-regulating effect of exogenous HSP70 on ROS generation and the interaction of the protein with the enzyme subunits. Our results confirmed the literature data concerning the ability of extracellular HSP70 to modulate NADPH oxidase activity and demonstrated for the first time an inhibitory effect of the protein on intracellular ROS generation in phagocytes.

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

Active Depletion of Host Cell Inhibitor-of-Apoptosis Proteins Triggers Apoptosis upon Baculovirus DNA Replication▿

PubMed Central

Vandergaast, Rianna; Schultz, Kimberly L. W.; Cerio, Rebecca J.; Friesen, Paul D.

2011-01-01

Apoptosis is an important antivirus defense by virtue of its impact on virus multiplication and pathogenesis. To define molecular mechanisms by which viruses are detected and the apoptotic response is initiated, we examined the antiviral role of host inhibitor-of-apoptosis (IAP) proteins in insect cells. We report here that the principal IAPs, DIAP1 and SfIAP, of the model insects Drosophila melanogaster and Spodoptera frugiperda, respectively, are rapidly depleted and thereby inactivated upon infection with the apoptosis-inducing baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). Virus-induced loss of these host IAPs triggered caspase activation and apoptotic death. Elevation of IAP levels by ectopic expression repressed caspase activation. Loss of host IAP in both species was triggered by AcMNPV DNA replication. By using selected inhibitors, we found that virus-induced IAP depletion was mediated in part by the proteasome but not by caspase cleavage. Consistent with this conclusion, mutagenic disruption of the SfIAP RING motif, which acts as an E3 ubiquitin ligase, stabilized SfIAP during infection. Importantly, SfIAP was also stabilized upon the removal of its 99-residue N-terminal leader, which serves as a critical determinant of IAP turnover. These data indicated that a host pathway initiated by virus DNA replication and acting through instability motifs embedded within IAP triggers IAP depletion and thereby causes apoptosis. Taken together, the results of our study suggest that host modulation of cellular IAP levels is a conserved mechanism by which insects mount an apoptotic antiviral response. Thus, host IAPs may function as critical sentinels of virus invasion in insects. PMID:21653668

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...

Endophyte-Mediated Modulation of Defense-Related Genes and Systemic Resistance in Withania somnifera (L.) Dunal under Alternaria alternata Stress.

PubMed

Mishra, Aradhana; Singh, Satyendra Pratap; Mahfooz, Sahil; Singh, Surendra Pratap; Bhattacharya, Arpita; Mishra, Nishtha; Nautiyal, C S

2018-04-15

Endophytes have been explored and found to perform an important role in plant health. However, their effects on the host physiological function and disease management remain elusive. The present study aimed to assess the potential effects of endophytes, singly as well as in combination, in Withania somnifera (L.) Dunal, on various physiological parameters and systemic defense mechanisms against Alternaria alternata Seeds primed with the endophytic bacteria Bacillus amyloliquefaciens and Pseudomonas fluorescens individually and in combination demonstrated an enhanced vigor index and germination rate. Interestingly, plants treated with the two-microbe combination showed the lowest plant mortality rate (28%) under A. alternata stress. Physiological profiling of treated plants showed improved photosynthesis, respiration, transpiration, and stomatal conductance under pathogenic stress. Additionally, these endophytes not only augmented defense enzymes and antioxidant activity in treated plants but also enhanced the expression of salicylic acid- and jasmonic acid-responsive genes in the stressed plants. Reductions in reactive oxygen species (ROS) and reactive nitrogen species (RNS) along with enhanced callose deposition in host plant leaves corroborated well with the above findings. Altogether, the study provides novel insights into the underlying mechanisms behind the tripartite interaction of endophyte- A. alternata - W. somnifera and underscores their ability to boost plant health under pathogen stress. IMPORTANCE W. somnifera is well known for producing several medicinally important secondary metabolites. These secondary metabolites are required by various pharmaceutical sectors to produce life-saving drugs. However, the cultivation of W. somnifera faces severe challenge from leaf spot disease caused by A. alternata To keep pace with the rising demand for this plant and considering its capacity for cultivation under field conditions, the present study was undertaken to develop approaches to enhance production of W. somnifera through intervention using endophytes. Application of bacterial endophytes not only suppresses the pathogenicity of A. alternata but also mitigates excessive ROS/RNS generation via enhanced physiological processes and antioxidant machinery. Expression profiling of plant defense-related genes further validates the efficacy of bacterial endophytes against leaf spot disease. Copyright © 2018 American Society for Microbiology.

Effect of Light Availability on the Interaction between Maritime Pine and the Pine Weevil: Light Drives Insect Feeding Behavior But Also the Defensive Capabilities of the Host

PubMed Central

Suárez-Vidal, Estefanía; López-Goldar, Xosé; Sampedro, Luis; Zas, Rafael

2017-01-01

Light is a major environmental factor that may determine the interaction between plants and herbivores in several ways, including top-down effects through changes in herbivore behavior and bottom-up effects mediated by alterations of plant physiology. Here we explored the relative contribution of these two regulation processes to the outcome of the interaction of pine trees with a major forest pest, the pine weevil (Hylobius abietis). We studied to what extent light availability influence insect feeding behavior and/or the ability of pines to produce induced defenses in response to herbivory. For this purpose, 3-year old Pinus pinaster plants from three contrasting populations were subjected to 6 days of experimental herbivory by the pine weevil under two levels of light availability (complete darkness or natural sunlight) independently applied to the plant and to the insect in a fully factorial design. Light availability strongly affected the pine weevil feeding behavior. The pine weevil fed more and caused larger feeding scars in darkness than under natural sunlight. Besides, under the more intense levels of weevil damage (i.e., those registered with insects in darkness), light availability also affected the pine’s ability to respond to insect feeding by producing induced resin defenses. These results were consistent across the three studied populations despite they differed in weevil susceptibility and inducibility of defenses. Morocco was the most damaged population and the one that induced more defensive compounds. Overall, results indicate that light availability modulates the outcome of the pine–weevil interactions through both bottom-up and top-down regulation mechanisms. PMID:28912787

Modulation of human alveolar macrophage properties by ozone exposure in vitro

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

Becker, S.; Madden, M.C.; Newman, S.L.

The study investigated changes in human alveolar macrophage (HAM) function after exposure in vitro to ozone (O3)(0.1-1.0 ppm for 2-4 hr). The functions studied reflect concern that O3 is detrimental to host defense mechanisms in the bronchoalveolar spaces. Exposure of HAM to O3 caused a concentration-dependent increase in release of prostaglandin E2(PGE2), an important modulator of inflammation, phagocytosis, and oxidative burst. Although phagocytosis of particulate immune complexes was decreased by O3, the authors found no change in the quantity of Fc receptors and complement receptors on the HAM surface. Superoxide (O2) production in response to phorbol ester was reduced aftermore » exposure of HAM to O3 while the basal O2 release in response to plastic adherence was not affected. Growth inhibition of the opportunistic yeast Cryptococcus neoformans by HAM was not affected by O3 exposure. The production of inflammatory mediators and immune modulators such as tumor necrosis factor-alpha, interleukin 1, and interleukin 6 were not induced by exposure to O3. However, compared to controls, O3-exposed HAM produced significantly lower levels of these cytokines when simulated with bacterial lipopolysaccharide (LPS).« less

Role of ND10 nuclear bodies in the chromatin repression of HSV-1.

PubMed

Gu, Haidong; Zheng, Yi

2016-04-05

Herpes simplex virus (HSV) is a neurotropic virus that establishes lifelong latent infection in human ganglion sensory neurons. This unique life cycle necessitates an intimate relation between the host defenses and virus counteractions over the long course of infection. Two important aspects of host anti-viral defense, nuclear substructure restriction and epigenetic chromatin regulation, have been intensively studied in the recent years. Upon viral DNA entering the nucleus, components of discrete nuclear bodies termed nuclear domain 10 (ND10), converge at viral DNA and place restrictions on viral gene expression. Meanwhile the infected cell mobilizes its histones and histone-associated repressors to force the viral DNA into nucleosome-like structures and also represses viral transcription. Both anti-viral strategies are negated by various HSV countermeasures. One HSV gene transactivator, infected cell protein 0 (ICP0), is a key player in antagonizing both the ND10 restriction and chromatin repression. On one hand, ICP0 uses its E3 ubiquitin ligase activity to target major ND10 components for proteasome-dependent degradation and thereafter disrupts the ND10 nuclear bodies. On the other hand, ICP0 participates in de-repressing the HSV chromatin by changing histone composition or modification and therefore activates viral transcription. Involvement of a single viral protein in two seemingly different pathways suggests that there is coordination in host anti-viral defense mechanisms and also cooperation in viral counteraction strategies. In this review, we summarize recent advances in understanding the role of chromatin regulation and ND10 dynamics in both lytic and latent HSV infection. We focus on the new observations showing that ND10 nuclear bodies play a critical role in cellular chromatin regulation. We intend to find the connections between the two major anti-viral defense pathways, chromatin remodeling and ND10 structure, in order to achieve a better understanding of how host orchestrates a concerted defense and how HSV adapts with and overcomes the host immunity.

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 reticulum stress interferes with host defenses and autophagy.« less

Facial markings in the social cuckoo wasp Polistes sulcifer: No support for the visual deception and the assessment hypotheses.

PubMed

Cini, Alessandro; Ortolani, Irene; Zechini, Luigi; Cervo, Rita

2015-02-01

Insect social parasites have to conquer a host colony by overcoming its defensive barriers. In addition to increased fighting abilities, many social parasites evolved sophisticated sensory deception mechanisms to elude host colonies defenses by exploiting host communication channels. Recently, it has been shown that the conspicuous facial markings of a paper wasp social parasite, Polistes sulcifer, decrease the aggressiveness of host foundresses. Two main hypotheses stand as explanations of this phenomenon: visual sensory deception (i.e. the black patterning reduces host aggression by exploiting the host visual communication system) and visual quality assessment (i.e. facial markings reduce aggressiveness as they signal the increased fighting ability of parasites). Through behavioral assays and morphological measurements we tested three predictions resulting from these hypotheses and found no support either for the visual sensory deception or for the quality assessment to explain the reduction in host aggressiveness towards the parasite. Our results suggest that other discrimination processes may explain the observed phenomenon. Copyright © 2014 Elsevier B.V. All rights reserved.

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...

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...

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.

A pocket guide to explorations of the defensin field.

PubMed

Selsted, Michael E

2007-01-01

Antimicrobial peptides are among the most ancient effectors of host defense. Intersecting lines of research demonstrate that life forms as diverse as plants, insects, and vertebrates employ antimicrobial peptides to kill or neutralize a wide variety of microbial species. Defensins, of which there are three structural sub-families, constitute a major category of host defense peptides in vertebrates. Presented here is a brief history of the emergence of the defensin field with an emphasis on the role of these peptides in mammalian innate immunity.

Pathogenesis of NEC: Role of the Innate and Adaptive Immune Response

PubMed Central

Denning, Timothy L.; Bhatia, Amina M.; Kane, Andrea F.; Patel, Ravi M.; Denning, Patricia L.

2017-01-01

Necrotizing enterocolitis (NEC) is a devastating disease in premature infants with high case fatality and significant morbidity among survivors. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. Here, we review the role of the innate and adaptive immune system in the pathophysiology of NEC. PMID:27940091

Candida albicans Chitin Increases Arginase-1 Activity in Human Macrophages, with an Impact on Macrophage Antimicrobial Functions.

PubMed

Wagener, Jeanette; MacCallum, Donna M; Brown, Gordon D; Gow, Neil A R

2017-01-24

The opportunistic human fungal pathogen Candida albicans can cause a variety of diseases, ranging from superficial mucosal infections to life-threatening systemic infections. Phagocytic cells of the innate immune response, such as neutrophils and macrophages, are important first-line responders to an infection and generate reactive oxygen and nitrogen species as part of their protective antimicrobial response. During an infection, host cells generate nitric oxide through the enzyme inducible nitric oxide synthase (iNOS) to kill the invading pathogen. Inside the phagocyte, iNOS competes with the enzyme arginase-1 for a common substrate, the amino acid l-arginine. Several pathogenic species, including bacteria and parasitic protozoans, actively modulate the production of nitric oxide by inducing their own arginases or the host's arginase activity to prevent the conversion of l-arginine to nitric oxide. We report here that C. albicans blocks nitric oxide production in human-monocyte-derived macrophages by induction of host arginase activity. We further determined that purified chitin (a fungal cell wall polysaccharide) and increased chitin exposure at the fungal cell wall surface induces this host arginase activity. Blocking the C. albicans-induced arginase activity with the arginase-specific substrate inhibitor Nω-hydroxy-nor-arginine (nor-NOHA) or the chitinase inhibitor bisdionin F restored nitric oxide production and increased the efficiency of fungal killing. Moreover, we determined that C. albicans influences macrophage polarization from a classically activated phenotype toward an alternatively activated phenotype, thereby reducing antimicrobial functions and mediating fungal survival. Therefore, C. albicans modulates l-arginine metabolism in macrophages during an infection, potentiating its own survival. The availability and metabolism of amino acids are increasingly recognized as crucial regulators of immune functions. In acute infections, the conversion of the "conditionally essential" amino acid l-arginine by the inducible nitric oxide synthase to nitric oxide is a resistance factor that is produced by the host to fight pathogens. Manipulation of these host defense mechanisms by the pathogen can be key to successful host invasion. We show here that the human opportunistic fungal pathogen Candida albicans influences l-arginine availability for nitric oxide production by induction of the substrate-competing host enzyme arginase-1. This led to a reduced production of nitric oxide and, moreover, reduced eradication of the fungus by human macrophages. We demonstrate that blocking of host arginase-1 activity restored nitric oxide production and increased the killing potential of macrophages. These results highlight the therapeutic potential of l-arginine metabolism in fungal diseases. Copyright © 2017 Wagener et al.

Vitamins for enhancing plant resistance.

PubMed

Boubakri, Hatem; Gargouri, Mahmoud; Mliki, Ahmed; Brini, Faiçal; Chong, Julie; Jbara, Moez

2016-09-01

This paper provides an overview on vitamins with inducing activities in plants, the molecular and cellular mechanisms implicated, and the hormonal signalling-network regulating this process. Moreover, it reports how vitamins might be part of the molecular events linked to induced resistance by the conventional elicitors. Induced resistance (IR), exploiting the plant innate-defense system is a sustainable strategy for plant disease control. In the last decade, vitamins have been proven to act as inducers of disease resistance, and these findings have received an important attention owing to their safety and cost effectiveness. Vitamins, including thiamine (TH, vitamin B1), riboflavin (RF, vitamin B2), menadione sodium bisulfite (MSB, vitamin K3), Para-aminobenzoic acid (PABA, vitamin Bx), and folic acid (FA, vitamin B9) provided an efficient protection against a wide range of pathogens through the modulation of specific host-defense facets. However, other vitamins, such as ascorbic acid (AA, vitamin C) and tocopherols (vitamin E), have been shown to be a part of the molecular mechanisms associated to IR. The present review is the first to summarize what vitamins are acting as inducers of disease resistance in plants and how could they be modulated by the conventional elicitors. Thus, this report provides an overview on the protective abilities of vitamins and the molecular and cellular mechanisms underlying their activities. Moreover, it describes the hormonal-signalling network regulating vitamin-signal transduction during IR. Finally, a biochemical model describing how vitamins are involved in the establishment of IR process is discussed.

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

“Parasite-induced aposematism” protects entomopathogenic nematode parasites against invertebrate enemies

PubMed Central

Fenton, Andy; Speed, Michael P.

2016-01-01

Aposematism is a well-known strategy in which prey defend themselves from predation by pairing defenses such as toxins, with warning signals that are often visually conspicuous color patterns. Here, we examine the possibility that aposematism can be induced in a host by colonies of infectious parasites in order to protect the parasites from the consequences of attacks on the host. Earlier studies show that avian predators are reluctant to feed on carcasses of host prey that are infected with the entomopathogenic nematode, Heterorhabditis bacteriophora. As the age of infection increases, the parasites kill and preserve the host and subsequently cause its color to change, becoming bright pink then red. Nematode colonies in dead hosts may also be vulnerable, however, to nocturnally active foragers that do not use vision in prey detection. Here, then we test a novel hypothesis that the nematode parasites also produce a warning odor, which functions to repel nocturnally active predators (in this case, the beetle Pterostichus madidus). We show that beetles decrease their feeding on infected insect prey as the age of infection increases and that olfactory cues associated with the infections are effective mechanisms for deterring beetle predation, even at very early stages of infection. We propose that “parasite-induced aposematism” from the nematodes serves to replace the antipredator defenses of the recently killed host. Because sessile carcasses are exposed to a greater range of predators than the live hosts, several alternative defense mechanisms are required to protect the colony, hence aposematic signals are likely diverse in such “parasite-induced aposematism.” PMID:27004015

Parasitoid-specific induction of plant responses to parasitized herbivores affects colonization by subsequent herbivores.

PubMed

Poelman, Erik H; Zheng, Si-Jun; Zhang, Zhao; Heemskerk, Nanda M; Cortesero, Anne-Marie; Dicke, Marcel

2011-12-06

Plants are exposed to a suite of herbivorous attackers that often arrive sequentially. Herbivory affects interactions between the host plants and subsequently attacking herbivores. Moreover, plants may respond to herbivory by emitting volatile organic compounds (VOCs) that attract carnivorous natural enemies of the herbivores. However, information borne by VOCs is ubiquitous and may attract carnivores, such as parasitoids, that differ in their effectiveness at releasing the plant from its herbivorous attackers. Furthermore, the development of parasitoids within their herbivorous hosts, attacking a given host plant, may influence the elicitation of defensive reactions in the host plant. This may, in turn, affect the behavior of subsequent herbivores attacking the host plant. Here, we show that the species identity of a parasitoid had a more significant effect on defense responses of Brassica oleracea plants than the species identity of the herbivorous hosts of the parasitoids. Consequently, B. oleracea plants that were damaged by caterpillars (Pieris spp.) parasitized by different parasitoid species varied in the degree to which diamondback moths (Plutella xylostella) selected the plants for oviposition. Attracting parasitoids in general benefitted the plants by reducing diamondback moth colonization. However, the species of parasitoid that parasitized the herbivore significantly affected the magnitude of this benefit by its species-specific effect on herbivore-plant interactions mediated by caterpillar regurgitant. Our findings show that information-mediated indirect defense may lead to unpredictable consequences for plants when considering trait-mediated effects of parasitized caterpillars on the host plant and their consequences because of community-wide responses to induced plants.

Polyglycine hydrolases secreted by pathogenic fungi

USDA-ARS?s Scientific Manuscript database

Pathogens are known to produce proteases that target host defense proteins. Here we describe polyglycine hydrolases, fungal proteases that selectively cleave glycine-glycine peptide bonds within the polyglycine interdomain linker of targeted plant defense chitinases. Polyglycine hydrolases were puri...

Epigenetic Mechanisms: An Emerging Player in Plant-Microbe Interactions.

PubMed

Zhu, Qian-Hao; Shan, Wei-Xing; Ayliffe, Michael A; Wang, Ming-Bo

2016-03-01

Plants have developed diverse molecular and cellular mechanisms to cope with a lifetime of exposure to a variety of pathogens. Host transcriptional reprogramming is a central part of plant defense upon pathogen recognition. Recent studies link DNA methylation and demethylation as well as chromatin remodeling by posttranslational histone modifications, including acetylation, methylation, and ubiquitination, to changes in the expression levels of defense genes upon pathogen challenge. Remarkably these inducible defense mechanisms can be primed prior to pathogen attack by epigenetic modifications and this heightened resistance state can be transmitted to subsequent generations by inheritance of these modification patterns. Beside the plant host, epigenetic mechanisms have also been implicated in virulence development of pathogens. This review highlights recent findings and insights into epigenetic mechanisms associated with interactions between plants and pathogens, in particular bacterial and fungal pathogens, and demonstrates the positive role they can have in promoting plant defense.

Endogenous small RNAs and antibacterial immunity in plants.

PubMed

Jin, Hailing

2008-08-06

Small RNAs are non-coding regulatory RNA molecules that control gene expression by mediating mRNA degradation, translational inhibition, or chromatin modification. Virus-derived small RNAs induce silencing of viral RNAs and are essential for antiviral defense in both animal and plant systems. The role of host endogenous small RNAs on antibacterial immunity has only recently been recognized. Host disease resistance and defense responses are achieved by activation and repression of a large array of genes. Certain endogenous small RNAs in plants, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are induced or repressed in response to pathogen attack and subsequently regulate the expression of genes involved in disease resistance and defense responses by mediating transcriptional or post-transcriptional gene silencing. Thus, these small RNAs play an important role in gene expression reprogramming in plant disease resistance and defense responses. This review focuses on the recent findings of plant endogenous small RNAs in antibacterial immunity.

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

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.

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.

Toll-like receptor cascade and gene polymorphism in host-pathogen interaction in Lyme disease.

PubMed

Rahman, Shusmita; Shering, Maria; Ogden, Nicholas H; Lindsay, Robbin; Badawi, Alaa

2016-01-01

Lyme disease (LD) risk occurs in North America and Europe where the tick vectors of the causal agent Borrelia burgdorferi sensu lato are found. It is associated with local and systemic manifestations, and has persistent posttreatment health complications in some individuals. The innate immune system likely plays a critical role in both host defense against B. burgdorferi and disease severity. Recognition of B. burgdorferi, activation of the innate immune system, production of proinflammatory cytokines, and modulation of the host adaptive responses are all initiated by Toll-like receptors (TLRs). A number of Borrelia outer-surface proteins (eg, OspA and OspB) are recognized by TLRs. Specifically, TLR1 and TLR2 were identified as the receptors most relevant to LD. Several functional single-nucleotide polymorphisms have been identified in TLR genes, and are associated with varying cytokines types and synthesis levels, altered pathogen recognition, and disruption of the downstream signaling cascade. These single-nucleotide polymorphism-related functional alterations are postulated to be linked to disease development and posttreatment persistent illness. Elucidating the role of TLRs in LD may facilitate a better understanding of disease pathogenesis and can provide an insight into novel therapeutic targets during active disease or postinfection and posttreatment stages.

Roles of Probiotic Lactobacilli Inclusion in Helping Piglets Establish Healthy Intestinal Inter-environment for Pathogen Defense.

PubMed

Yang, Jiajun; Qian, Kun; Wang, Chonglong; Wu, Yijing

2018-06-01

The gastrointestinal tract of pigs is densely populated with microorganisms that closely interact with the host and with ingested feed. Gut microbiota benefits the host by providing nutrients from dietary substrates and modulating the development and function of the digestive and immune systems. An optimized gastrointestinal microbiome is crucial for pigs' health, and establishment of the microbiome in piglets is especially important for growth and disease resistance. However, the microbiome in the gastrointestinal tract of piglets is immature and easily influenced by the environment. Supplementing the microbiome of piglets with probiotic bacteria such as Lactobacillus could help create an optimized microbiome by improving the abundance and number of lactobacilli and other indigenous probiotic bacteria. Dominant indigenous probiotic bacteria could improve piglets' growth and immunity through certain cascade signal transduction pathways. The piglet body provides a permissive habitat and nutrients for bacterial colonization and growth. In return, probiotic bacteria produce prebiotics such as short-chain fatty acids and bacteriocins that benefit piglets by enhancing their growth and reducing their risk of enteric infection by pathogens. A comprehensive understanding of the interactions between piglets and members of their gut microbiota will help develop new dietary interventions that can enhance piglets' growth, protect piglets from enteric diseases caused by pathogenic bacteria, and maximize host feed utilization.

CD44 deficiency leads to decreased proinflammatory cytokine production in lung induced by PCV2 in mice.

PubMed

Fu, Qiang; Hou, Linbing; Xiao, Pingping; Guo, Chunhe; Chen, Yaosheng; Liu, Xiaohong

2014-12-01

Porcine circovirus type 2 (PCV2) is the primary etiological agent of postweaning multisystemic wasting syndrome (PMWS). CD44 is a widely expressed class I transmembrane glycoprotein implicated in immunological and inflammatory responses. In previous studies, the role of CD44 in host defense against microorganism infection remains controversial. The role of CD44 in host defense against PCV2 infection has never been studied before. In this study, we investigated the role of CD44 in the development of pneumonia induced by PCV2 in mice model. Upon infection, CD44 mRNA level in lung tissue was upregulated, and we confirmed a detrimental role of CD44 in host defense against PCV2 infection. The results demonstrated that CD44 deficiency could result in decreased proinflammatory cytokine production in lung induced by PCV2 in mice, suggesting a previously unrecognized role for CD44 in the development of pneumonia response to PCV2 infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA.

PubMed

Alvarez, Luis A; Kovačič, Lidija; Rodríguez, Javier; Gosemann, Jan-Hendrik; Kubica, Malgorzata; Pircalabioru, Gratiela G; Friedmacher, Florian; Cean, Ada; Ghişe, Alina; Sărăndan, Mihai B; Puri, Prem; Daff, Simon; Plettner, Erika; von Kriegsheim, Alex; Bourke, Billy; Knaus, Ulla G

2016-09-13

Strengthening the host immune system to fully exploit its potential as antimicrobial defense is vital in countering antibiotic resistance. Chemical compounds released during bidirectional host-pathogen cross-talk, which follows a sensing-response paradigm, can serve as protective mediators. A potent, diffusible messenger is hydrogen peroxide (H2O2), but its consequences on extracellular pathogens are unknown. Here we show that H2O2, released by the host on pathogen contact, subverts the tyrosine signaling network of a number of bacteria accustomed to low-oxygen environments. This defense mechanism uses heme-containing bacterial enzymes with peroxidase-like activity to facilitate phosphotyrosine (p-Tyr) oxidation. An intrabacterial reaction converts p-Tyr to protein-bound dopa (PB-DOPA) via a tyrosinyl radical intermediate, thereby altering antioxidant defense and inactivating enzymes involved in polysaccharide biosynthesis and metabolism. Disruption of bacterial signaling by DOPA modification reveals an infection containment strategy that weakens bacterial fitness and could be a blueprint for antivirulence approaches.

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

Mountain pine beetles colonizing historical and naive host trees are associated with a bacterial community highly enriched in genes contributing to terpene metabolism.

PubMed

Adams, Aaron S; Aylward, Frank O; Adams, Sandye M; Erbilgin, Nadir; Aukema, Brian H; Currie, Cameron R; Suen, Garret; Raffa, Kenneth F

2013-06-01

The mountain pine beetle, Dendroctonus ponderosae, is a subcortical herbivore native to western North America that can kill healthy conifers by overcoming host tree defenses, which consist largely of high terpene concentrations. The mechanisms by which these beetles contend with toxic compounds are not well understood. Here, we explore a component of the hypothesis that beetle-associated bacterial symbionts contribute to the ability of D. ponderosae to overcome tree defenses by assisting with terpene detoxification. Such symbionts may facilitate host tree transitions during range expansions currently being driven by climate change. For example, this insect has recently breached the historical geophysical barrier of the Canadian Rocky Mountains, providing access to näive tree hosts and unprecedented connectivity to eastern forests. We use culture-independent techniques to describe the bacterial community associated with D. ponderosae beetles and their galleries from their historical host, Pinus contorta, and their more recent host, hybrid P. contorta-Pinus banksiana. We show that these communities are enriched with genes involved in terpene degradation compared with other plant biomass-processing microbial communities. These pine beetle microbial communities are dominated by members of the genera Pseudomonas, Rahnella, Serratia, and Burkholderia, and the majority of genes involved in terpene degradation belong to these genera. Our work provides the first metagenome of bacterial communities associated with a bark beetle and is consistent with a potential microbial contribution to detoxification of tree defenses needed to survive the subcortical environment.

Direct and Indirect Antimicrobial Activities of Neuropeptides and their Therapeutic Potential

PubMed Central

Augustyniak, Daria; Nowak, Judyta; Lundy, Fionnuala T

2012-01-01

As global resistance to conventional antibiotics rises we need to develop new strategies to develop future novel therapeutics. In our quest to design novel anti-infectives and antimicrobials it is of interest to investigate host-pathogen interactions and learn from the complexity of host defense strategies that have evolved over millennia. A myriad of host defense molecules are now known to play a role in protection against human infection. However, the interaction between host and pathogen is recognized to be a multifaceted one, involving countless host proteins, including several families of peptides. The regulation of infection and inflammation by multiple peptide families may represent an evolutionary failsafe in terms of functional degeneracy and emphasizes the significance of host defense in survival. One such family is the neuropeptides (NPs), which are conventionally defined as peptide neurotransmitters but have recently been shown to be pleiotropic molecules that are integral components of the nervous and immune systems. In this review we address the antimicrobial and anti-infective effects of NPs both in vitro and in vivo and discuss their potential therapeutic usefulness in overcoming infectious diseases. With improved understanding of the efficacy of NPs, these molecules could become an important part of our arsenal of weapons in the treatment of infection and inflammation. It is envisaged that targeted therapy approaches that selectively exploit the anti-infective, antimicrobial and immunomodulatory properties of NPs could become useful adjuncts to our current therapeutic modalities. PMID:23305360

A TNF-Regulated Recombinatorial Macrophage Immune Receptor Implicated in Granuloma Formation in Tuberculosis

PubMed Central

Streich, Roswita; Breysach, Caroline; Raddatz, Dirk; Oniga, Septimia; Peccerella, Teresa; Findeisen, Peter; Kzhyshkowska, Julia; Gratchev, Alexei; Schweyer, Stefan; Saunders, Bernadette; Wessels, Johannes T.; Möbius, Wiebke; Keane, Joseph; Becker, Heinz; Ganser, Arnold; Neumaier, Michael; Kaminski, Wolfgang E.

2011-01-01

Macrophages play a central role in host defense against mycobacterial infection and anti- TNF therapy is associated with granuloma disorganization and reactivation of tuberculosis in humans. Here, we provide evidence for the presence of a T cell receptor (TCR) αβ based recombinatorial immune receptor in subpopulations of human and mouse monocytes and macrophages. In vitro, we find that the macrophage-TCRαβ induces the release of CCL2 and modulates phagocytosis. TNF blockade suppresses macrophage-TCRαβ expression. Infection of macrophages from healthy individuals with mycobacteria triggers formation of clusters that express restricted TCR Vβ repertoires. In vivo, TCRαβ bearing macrophages abundantly accumulate at the inner host-pathogen contact zone of caseous granulomas from patients with lung tuberculosis. In chimeric mouse models, deletion of the variable macrophage-TCRαβ or TNF is associated with structurally compromised granulomas of pulmonary tuberculosis even in the presence of intact T cells. These results uncover a TNF-regulated recombinatorial immune receptor in monocytes/macrophages and demonstrate its implication in granuloma formation in tuberculosis. PMID:22114556

Induced Genome-Wide Binding of Three Arabidopsis WRKY Transcription Factors during Early MAMP-Triggered Immunity

PubMed Central

Birkenbihl, Rainer P.; Kracher, Barbara; Roccaro, Mario

2017-01-01

During microbial-associated molecular pattern-triggered immunity (MTI), molecules derived from microbes are perceived by cell surface receptors and upon signaling to the nucleus initiate a massive transcriptional reprogramming critical to mount an appropriate host defense response. WRKY transcription factors play an important role in regulating these transcriptional processes. Here, we determined on a genome-wide scale the flg22-induced in vivo DNA binding dynamics of three of the most prominent WRKY factors, WRKY18, WRKY40, and WRKY33. The three WRKY factors each bound to more than 1000 gene loci predominantly at W-box elements, the known WRKY binding motif. Binding occurred mainly in the 500-bp promoter regions of these genes. Many of the targeted genes are involved in signal perception and transduction not only during MTI but also upon damage-associated molecular pattern-triggered immunity, providing a mechanistic link between these functionally interconnected basal defense pathways. Among the additional targets were genes involved in the production of indolic secondary metabolites and in modulating distinct plant hormone pathways. Importantly, among the targeted genes were numerous transcription factors, encoding predominantly ethylene response factors, active during early MTI, and WRKY factors, supporting the previously hypothesized existence of a WRKY subregulatory network. Transcriptional analysis revealed that WRKY18 and WRKY40 function redundantly as negative regulators of flg22-induced genes often to prevent exaggerated defense responses. PMID:28011690

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.

Avian host defense peptides.

PubMed

Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

2013-11-01

Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds. Copyright © 2013 Elsevier Ltd. All rights reserved.

MTBE TREATMENT TECHNOLOGIES DEMONSTRATION PROJECTS

EPA Science Inventory

The NRMRL, in collaboration with the State of California, and Department of Defense research program (ESTCP) is hosting a field-scale evaluation of cleanup technologies at the Department of Defense National Environmental Technology Test Site at Port Hueneme California. EPA has ...

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.

Mechanisms employed by retroviruses to exploit host factors for translational control of a complicated proteome

PubMed Central

Bolinger, Cheryl; Boris-Lawrie, Kathleen

2009-01-01

Retroviruses have evolved multiple strategies to direct the synthesis of a complex proteome from a single primary transcript. Their mechanisms are modulated by a breadth of virus-host interactions, which are of significant fundamental interest because they ultimately affect the efficiency of virus replication and disease pathogenesis. Motifs located within the untranslated region (UTR) of the retroviral RNA have established roles in transcriptional trans-activation, RNA packaging, and genome reverse transcription; and a growing literature has revealed a necessary role of the UTR in modulating the efficiency of viral protein synthesis. Examples include a 5' UTR post-transcriptional control element (PCE), present in at least eight retroviruses, that interacts with cellular RNA helicase A to facilitate cap-dependent polyribosome association; and 3' UTR constitutive transport element (CTE) of Mason-Pfizer monkey virus that interacts with Tap/NXF1 and SR protein 9G8 to facilitate RNA export and translational utilization. By contrast, nuclear protein hnRNP E1 negatively modulates HIV-1 Gag, Env, and Rev protein synthesis. Alternative initiation strategies by ribosomal frameshifting and leaky scanning enable polycistronic translation of the cap-dependent viral transcript. Other studies posit cap-independent translation initiation by internal ribosome entry at structural features of the 5' UTR of selected retroviruses. The retroviral armamentarium also commands mechanisms to counter cellular post-transcriptional innate defenses, including protein kinase R, 2',5'-oligoadenylate synthetase and the small RNA pathway. This review will discuss recent and historically-recognized insights into retrovirus translational control. The expanding knowledge of retroviral post-transcriptional control is vital to understanding the biology of the retroviral proteome. In a broad perspective, each new insight offers a prospective target for antiviral therapy and strategic improvement of gene transfer vectors. PMID:19166625

Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization.

PubMed

Hyre, Amanda N; Kavanagh, Kylie; Kock, Nancy D; Donati, George L; Subashchandrabose, Sargurunathan

2017-03-01

Urinary tract infection (UTI) is a major global infectious disease affecting millions of people annually. Human urinary copper (Cu) content is elevated during UTI caused by uropathogenic Escherichia coli (UPEC). UPEC upregulates the expression of Cu efflux genes during clinical UTI in patients as an adaptive response to host-derived Cu. Whether Cu is mobilized to urine as a host response to UTI and its role in protection against UTI remain unresolved. To address these questions, we tested the hypothesis that Cu is a host effector mobilized to urine during UTI to limit bacterial growth. Our results reveal that Cu is mobilized to urine during UTI caused by the major uropathogens Proteus mirabilis and Klebsiella pneumoniae , in addition to UPEC, in humans. Ceruloplasmin, a Cu-containing ferroxidase, is found at higher levels in UTI urine than in healthy control urine and serves as the molecular source of urinary Cu during UTI. Our results demonstrate that ceruloplasmin decreases the bioavailability of iron in urine by a transferrin-dependent mechanism. Experimental UTI with UPEC in nonhuman primates recapitulates the increased urinary Cu content observed during clinical UTI. Furthermore, Cu-deficient mice are highly colonized by UPEC, indicating that Cu is involved in the limiting of bacterial growth within the urinary tract. Collectively, our results indicate that Cu is a host effector that is involved in protection against pathogen colonization of the urinary tract. Because urinary Cu levels are amenable to modulation, augmentation of the Cu-based host defense against UTI represents a novel approach to limiting bacterial colonization during UTI. Copyright © 2017 American Society for Microbiology.

Archaeal Extrachromosomal Genetic Elements

PubMed Central

Wang, Haina; Peng, Nan; Shah, Shiraz A.

2015-01-01

SUMMARY Research on archaeal extrachromosomal genetic elements (ECEs) has progressed rapidly in the past decade. To date, over 60 archaeal viruses and 60 plasmids have been isolated. These archaeal viruses exhibit an exceptional diversity in morphology, with a wide array of shapes, such as spindles, rods, filaments, spheres, head-tails, bottles, and droplets, and some of these new viruses have been classified into one order, 10 families, and 16 genera. Investigation of model archaeal viruses has yielded important insights into mechanisms underlining various steps in the viral life cycle, including infection, DNA replication and transcription, and virion egression. Many of these mechanisms are unprecedented for any known bacterial or eukaryal viruses. Studies of plasmids isolated from different archaeal hosts have also revealed a striking diversity in gene content and innovation in replication strategies. Highly divergent replication proteins are identified in both viral and plasmid genomes. Genomic studies of archaeal ECEs have revealed a modular sequence structure in which modules of DNA sequence are exchangeable within, as well as among, plasmid families and probably also between viruses and plasmids. In particular, it has been suggested that ECE-host interactions have shaped the coevolution of ECEs and their archaeal hosts. Furthermore, archaeal hosts have developed defense systems, including the innate restriction-modification (R-M) system and the adaptive CRISPR (clustered regularly interspaced short palindromic repeats) system, to restrict invasive plasmids and viruses. Together, these interactions permit a delicate balance between ECEs and their hosts, which is vitally important for maintaining an innovative gene reservoir carried by ECEs. In conclusion, while research on archaeal ECEs has just started to unravel the molecular biology of these genetic entities and their interactions with archaeal hosts, it is expected to accelerate in the next decade. PMID:25694123

Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

PubMed Central

Barber, Amelia E.; Norton, J. Paul; Wiles, Travis J.

2016-01-01

SUMMARY Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic Escherichia coli (UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host. PMID:26935136

Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

PubMed

Fernandes, Maria Cecilia; Dillon, Laura A L; Belew, Ashton Trey; Bravo, Hector Corrada; Mosser, David M; El-Sayed, Najib M

2016-05-10

Macrophages are mononuclear phagocytes that constitute a first line of defense against pathogens. While lethal to many microbes, they are the primary host cells of Leishmania spp. parasites, the obligate intracellular pathogens that cause leishmaniasis. We conducted transcriptomic profiling of two Leishmania species and the human macrophage over the course of intracellular infection by using high-throughput RNA sequencing to characterize the global gene expression changes and reprogramming events that underlie the interactions between the pathogen and its host. A systematic exclusion of the generic effects of large-particle phagocytosis revealed a vigorous, parasite-specific response of the human macrophage early in the infection that was greatly tempered at later time points. An analogous temporal expression pattern was observed with the parasite, suggesting that much of the reprogramming that occurs as parasites transform into intracellular forms generally stabilizes shortly after entry. Following that, the parasite establishes an intracellular niche within macrophages, with minimal communication between the parasite and the host cell later during the infection. No significant difference was observed between parasite species transcriptomes or in the transcriptional response of macrophages infected with each species. Our comparative analysis of gene expression changes that occur as mouse and human macrophages are infected by Leishmania spp. points toward a general signature of the Leishmania-macrophage infectome. Little is known about the transcriptional changes that occur within mammalian cells harboring intracellular pathogens. This study characterizes the gene expression signatures of Leishmania spp. parasites and the coordinated response of infected human macrophages as the pathogen enters and persists within them. After accounting for the generic effects of large-particle phagocytosis, we observed a parasite-specific response of the human macrophages early in infection that was reduced at later time points. A similar expression pattern was observed in the parasites. Our analyses provide specific insights into the interplay between human macrophages and Leishmania parasites and constitute an important general resource for the study of how pathogens evade host defenses and modulate the functions of the cell to survive intracellularly. Copyright © 2016 Fernandes et al.

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.

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

Potential Sabotage of Host Cell Physiology by Apicomplexan Parasites for Their Survival Benefits

PubMed Central

Chakraborty, Shalini; Roy, Sonti; Mistry, Hiral Uday; Murthy, Shweta; George, Neena; Bhandari, Vasundhra; Sharma, Paresh

2017-01-01

Plasmodium, Toxoplasma, Cryptosporidium, Babesia, and Theileria are the major apicomplexan parasites affecting humans or animals worldwide. These pathogens represent an excellent example of host manipulators who can overturn host signaling pathways for their survival. They infect different types of host cells and take charge of the host machinery to gain nutrients and prevent itself from host attack. The mechanisms by which these pathogens modulate the host signaling pathways are well studied for Plasmodium, Toxoplasma, Cryptosporidium, and Theileria, except for limited studies on Babesia. Theileria is a unique pathogen taking into account the way it modulates host cell transformation, resulting in its clonal expansion. These parasites majorly modulate similar host signaling pathways, however, the disease outcome and effect is different among them. In this review, we discuss the approaches of these apicomplexan to manipulate the host–parasite clearance pathways during infection, invasion, survival, and egress. PMID:29081773

Self-esteem modulates amygdala-ventrolateral prefrontal cortex connectivity in response to mortality threats.

PubMed

Yanagisawa, Kuniaki; Abe, Nobuhito; Kashima, Emiko S; Nomura, Michio

2016-03-01

Reminders of death often elicit defensive responses in individuals, especially among those with low self-esteem. Although empirical evidence indicates that self-esteem serves as a buffer against mortality threats, the precise neural mechanism underlying this effect remains unknown. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that self-esteem modulates neural responses to death-related stimuli, especially functional connectivity within the limbic-frontal circuitry, thereby affecting subsequent defensive reactions. As predicted, individuals with high self-esteem subjected to a mortality threat exhibited increased amygdala-ventrolateral prefrontal cortex (VLPFC) connectivity during the processing of death-related stimuli compared with individuals who have low self-esteem. Further analysis revealed that stronger functional connectivity between the amygdala and the VLPFC predicted a subsequent decline in responding defensively to those who threaten one's beliefs. These results suggest that the amygdala-VLPFC interaction, which is modulated by self-esteem, can reduce the defensiveness caused by death-related stimuli, thereby providing a neural explanation for why individuals with high self-esteem exhibit less defensive reactions to mortality threats. (c) 2016 APA, all rights reserved).

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

Immunomodulatory activity of plant residues on ovine neutrophils.

PubMed

Farinacci, Maura; Colitti, Monica; Sgorlon, Sandy; Stefanon, Bruno

2008-11-15

Neutrophils play an essential role in host defense and inflammation. Plants have long been used to improve the immune function, but for most of them specific investigations on animal health are lacking. In the present study, water and hydroethanolic extracts from 11 plant wastes have been screened on immune responses of ovine neutrophils. Eight sheep clinically healthy, not lactating, non-pregnant were selected and used for the experiment. Freshly isolated neutrophils were incubated with the extracts of the residues at increasing doses, and then they were tested for adhesion and superoxide production induced with PMA. The residues of Larix decidua, Thymus vulgaris, Salix alba, Sinupret, Helianthus annuus, Mangifera indica modulated the neutrophil immune functions, moreover, Larix decidua, Thymus vulgaris and Salix alba presented the highest anti-inflammatory activity.

The genome biology of phytoplasma: modulators of plants and insects.

PubMed

Sugio, Akiko; Hogenhout, Saskia A

2012-06-01

Phytoplasmas are bacterial pathogens of plants that are transmitted by insects. These bacteria uniquely multiply intracellularly in both plants (Plantae) and insects (Animalia). Similarly to bacterial endosymbionts, phytoplasmas have reduced genomes with limited metabolic capabilities. Nonetheless, the chromosomes of many phytoplasmas are rich in repeated DNA consisting of mobile elements. Phytoplasmas produce an arsenal of effectors most of which are encoded on these mobile elements and on plasmids. These effectors target conserved plant transcription factors resulting in witches' broom and leafy flower symptoms and suppression of plant defense to insect vectors that transmit the phytoplasmas. Future studies of these fascinating microbes will generate a wealth of new knowledge about forces that shape genomes and microbial interactions with multicellular hosts. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dendritic Cells: A Double-Edged Sword in Immune Responses during Chagas Disease

PubMed Central

Gil-Jaramillo, Natalia; Motta, Flávia N.; Favali, Cecília B. F.; Bastos, Izabela M. D.; Santana, Jaime M.

2016-01-01

Dendritic cells (DCs) are the most important member of the antigen presenting cells group due to their ability to recognize antigen at the infection site and their high specialized antigen internalization capacity. These cells have central role in connecting the innate and adaptive immune responses against Trypanosoma cruzi, the causative agent of Chagas disease. These first line defense cells modulate host immune response depending on type, maturation level, cytokine milieu and DC receptor involved in the interactions with T. cruzi, influencing the development of the disease clinic forms. Here, we present a review of DCs–T. cruzi interactions both in human and murine models, pointing out the parasite ability to manipulate DCs activity for the purpose of evading innate immune response and assuring its own survival and persistence. PMID:27471496

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 .

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.

Transition metals at the host–pathogen interface: How Neisseria exploit human metalloproteins for acquiring iron and zinc

PubMed Central

Neumann, Wilma; Hadley, Rose C.; Nolan, Elizabeth M.

2017-01-01

Transition metals are essential nutrients for all organisms and important players in the host-microbe interaction. During bacterial infection, a tug-of-war between the host and microbe for nutrient metals occurs: the host innate immune system responds to the pathogen by reducing metal availability and the pathogen tries to outmaneuver this response. The outcome of this competition, which involves metal-sequestering host-defense proteins and microbial metal acquisition machinery, is an important variable for whether infection occurs. One strategy bacterial pathogens employ to overcome metal restriction involves hijacking abundant host metalloproteins. The obligate human pathogens Neisseria spp. express TonB-dependent transport systems that capture human metalloproteins, extract the bound metal ions, and deliver these nutrients into the bacterial cell. This Essay highlights structural and mechanistic investigations that provide insights into how Neisseria acquire iron from the Fe(III)-transport protein transferrin, the Fe(III)-chelating host-defense protein lactoferrin, and the oxygen-transport protein hemoglobin, and obtain zinc from the metal-sequestering antimicrobial protein calprotectin. PMID:28487398

Changing roles of eosinophils in health and disease.

PubMed

Furuta, Glenn T; Atkins, F Dan; Lee, Nancy A; Lee, James J

2014-07-01

To review and highlight the unappreciated roles of eosinophils suggested by recent studies. The literature, unpublished observations, and insights by the authors. Basic studies of mouse models and patient-based clinical studies of disease. Eosinophils are often thought of as destructive end-stage effector cells primarily linked to parasite host defense and dysregulated immune responses associated with allergic diseases, such as asthma. However, recent studies (ie, research focused on mechanisms of action and translational studies examining disease/inflammatory pathways) are suggesting far more complex roles for eosinophils. The goal of this review is 3-fold. (1) The authors examine the dynamic history of eosinophils and how physicians over time used this information to formulate defining hypotheses. Particular emphasis is placed on recent studies challenging the parochial view of host defense in favor of roles maintaining homeostasis through immune modulation and tissue remodeling/repair. (2) They discuss diagnostic approaches to assess eosinophils in clinical settings as a means of disease identification and subsequently as a measurement of disease severity. (3) They examine how contemporary views of eosinophils and their perceived roles in diseases have led to specific therapeutic strategies. The emphasis is to review the successes and failures of these strategies as the basis of formulating future clinical studies targeting eosinophils as potential therapies of disease. Despite the complexities of eosinophil-mediated activities and the less than overwhelming success of initial attempts targeting these cells, eosinophils remain a potentially important focal target of disease diagnosis and subsequent treatment strategies. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

PubMed

Roger, Thierry; Schneider, Anina; Weier, Manuela; Sweep, Fred C G J; Le Roy, Didier; Bernhagen, Jürgen; Calandra, Thierry; Giannoni, Eric

2016-02-23

The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.

Modification of tissue-factor mRNA and protein response to thrombin and interleukin 1 by high glucose in cultured human endothelial cells.

PubMed

Boeri, D; Almus, F E; Maiello, M; Cagliero, E; Rao, L V; Lorenzi, M

1989-02-01

Because diabetic vascular disease is accompanied by a state of hypercoagulability, manifested by increased thrombin activity and foci of intravascular coagulation, we investigated whether a specific procoagulant property of the endothelium--production and surface expression of tissue factor--is modified by elevated glucose concentrations. In unperturbed human vascular endothelial cells, tissue factor mRNA and expression of the functional protein were undetectable and were not induced by 10-12 days of exposure to 30 mM glucose. In thrombin-stimulated cultures, tissue-factor expression was related inversely to cellular density, with confluent cultures producing (per 10(5) cells) half the amount of tissue factor measured in sparse cultures. Cells exposed to high glucose and studied when cell number and thymidine incorporation were identical to control cells manifested increased tissue-factor mRNA level and functional protein production in response to thrombin (P = .002). This effect was not attributable to hypertonicity and was not observed after short exposure to high glucose. In contrast, the tissue-factor response to interleukin 1, a modulator of endothelial function in the context of host defense, was decreased in cells cultured in high glucose (P = .04). These findings indicate that exposure to high glucose can alter tissue-factor gene expression in perturbed vascular endothelium. The reciprocal effects of high glucose on the tissue-factor response to thrombin and interleukin 1 points to different pathways of tissue-factor stimulation by the two agents and suggests functional consequences pertinent to the increased thrombin activity and compromised host-defense mechanisms observed in diabetes.

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.

The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation of Dectin-1 Expression.

PubMed

Gresnigt, Mark S; Jaeger, Martin; Subbarao Malireddi, R K; Rasid, Orhan; Jouvion, Grégory; Fitting, Catherine; Melchers, Willem J G; Kanneganti, Thirumala-Devi; Carvalho, Agostinho; Ibrahim-Granet, Oumaima; van de Veerdonk, Frank L

2017-01-01

One of the major life-threatening infections for which severely immunocompromised patients are at risk is invasive aspergillosis (IA). Despite the current treatment options, the increasing antifungal resistance and poor outcome highlight the need for novel therapeutic strategies to improve outcome of patients with IA. In the current study, we investigated whether and how the intracellular pattern recognition receptor NOD1 is involved in host defense against Aspergillus fumigatus . When exploring the role of NOD1 in an experimental mouse model, we found that Nod1 -/- mice were protected against IA and demonstrated reduced fungal outgrowth in the lungs. We found that macrophages derived from bone marrow of Nod1 -/- mice were more efficiently inducing reactive oxygen species and cytokines in response to Aspergillus . Most strikingly, these cells were highly potent in killing A. fumigatus compared with wild-type cells. In line, human macrophages in which NOD1 was silenced demonstrated augmented Aspergillus killing and NOD1 stimulation decreased fungal killing. The differentially altered killing capacity of NOD1 silencing versus NOD1 activation was associated with alterations in dectin-1 expression, with activation of NOD1 reducing dectin-1 expression. Furthermore, we were able to demonstrate that Nod1 -/- mice have elevated dectin-1 expression in the lung and bone marrow, and silencing of NOD1 gene expression in human macrophages increases dectin-1 expression. The enhanced dectin-1 expression may be the mechanism of enhanced fungal killing of Nod1 -/- cells and human cells in which NOD1 was silenced, since blockade of dectin-1 reversed the augmented killing in these cells. Collectively, our data demonstrate that NOD1 receptor plays an inhibitory role in the host defense against Aspergillus . This provides a rationale to develop novel immunotherapeutic strategies for treatment of aspergillosis that target the NOD1 receptor, to enhance the efficiency of host immune cells to clear the infection by increasing fungal killing and cytokine responses.

The Rice Transcription Factor WRKY53 Suppresses Herbivore-Induced Defenses by Acting as a Negative Feedback Modulator of Mitogen-Activated Protein Kinase Activity1

PubMed Central

Hu, Lingfei; Ye, Meng; Zhang, Tongfang; Zhou, Guoxin; Wang, Qi; Lu, Jing

2015-01-01

The mechanisms by which herbivore-attacked plants activate their defenses are well studied. By contrast, little is known about the regulatory mechanisms that allow them to control their defensive investment and avoid a defensive overshoot. We characterized a rice (Oryza sativa) WRKY gene, OsWRKY53, whose expression is rapidly induced upon wounding and induced in a delayed fashion upon attack by the striped stem borer (SSB) Chilo suppressalis. The transcript levels of OsWRKY53 are independent of endogenous jasmonic acid but positively regulated by the mitogen-activated protein kinases OsMPK3/OsMPK6. OsWRKY53 physically interacts with OsMPK3/OsMPK6 and suppresses their activity in vitro. By consequence, it modulates the expression of defensive, MPK-regulated WRKYs and thereby reduces jasmonic acid, jasmonoyl-isoleucine, and ethylene induction. This phytohormonal reconfiguration is associated with a reduction in trypsin protease inhibitor activity and improved SSB performance. OsWRKY53 is also shown to be a negative regulator of plant growth. Taken together, these results show that OsWRKY53 functions as a negative feedback modulator of MPK3/MPK6 and thereby acts as an early suppressor of induced defenses. OsWRKY53 therefore enables rice plants to control the magnitude of their defensive investment during early signaling. PMID:26453434

Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

PubMed

Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

2010-12-01

A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

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

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.

Pathogen Trojan Horse Delivers Bioactive Host Protein to Alter Maize Anther Cell Behavior in Situ.

PubMed

van der Linde, Karina; Timofejeva, Ljudmilla; Egger, Rachel L; Ilau, Birger; Hammond, Reza; Teng, Chong; Meyers, Blake C; Doehlemann, Gunther; Walbot, Virginia

2018-03-01

Small proteins are crucial signals during development, host defense, and physiology. The highly spatiotemporal restricted functions of signaling proteins remain challenging to study in planta. The several month span required to assess transgene expression, particularly in flowers, combined with the uncertainties from transgene position effects and ubiquitous or overexpression, makes monitoring of spatiotemporally restricted signaling proteins lengthy and difficult. This situation could be rectified with a transient assay in which protein deployment is tightly controlled spatially and temporally in planta to assess protein functions, timing, and cellular targets as well as to facilitate rapid mutagenesis to define functional protein domains. In maize ( Zea mays ), secreted ZmMAC1 (MULTIPLE ARCHESPORIAL CELLS1) was proposed to trigger somatic niche formation during anther development by participating in a ligand-receptor module. Inspired by Homer's Trojan horse myth, we engineered a protein delivery system that exploits the secretory capabilities of the maize smut fungus Ustilago maydis , to allow protein delivery to individual cells in certain cell layers at precise time points. Pathogen-supplied ZmMAC1 cell-autonomously corrected both somatic cell division and differentiation defects in mutant Zm mac1-1 anthers. These results suggest that exploiting host-pathogen interactions may become a generally useful method for targeting host proteins to cell and tissue types to clarify cellular autonomy and to analyze steps in cell responses. © 2018 American Society of Plant Biologists. All rights reserved.

Diversity within diversity: Parasite species richness in poison frogs assessed by transcriptomics.

PubMed

Santos, Juan C; Tarvin, Rebecca D; O'Connell, Lauren A; Blackburn, David C; Coloma, Luis A

2018-08-01

Symbionts (e.g., endoparasites and commensals) play an integral role in their host's ecology, yet in many cases their diversity is likely underestimated. Although endoparasites are traditionally characterized using morphology, sequences of conserved genes, and shotgun metagenomics, host transcriptomes constitute an underused resource to identify these organisms' diversity. By isolating non-host transcripts from host transcriptomes, individual host tissues can now simultaneously reveal their endoparasite species richness (i.e., number of different taxa) and provide insights into parasite gene expression. These approaches can be used in host taxa whose endoparasites are mostly unknown, such as those of tropical amphibians. Here, we focus on the poison frogs (Dendrobatidae) as hosts, which are a Neotropical clade known for their bright coloration and defensive alkaloids. These toxins are an effective protection against vertebrate predators (e.g., snakes and birds), bacteria, and skin-biting ectoparasites (e.g., mosquitoes); however, little is known about their deterrence against eukaryotic endoparasites. With de novo transcriptomes of dendrobatids, we developed a bioinformatics pipeline for endoparasite identification that uses host annotated RNA-seq data and set of a priori parasite taxonomic terms, which are used to mine for specific endoparasites. We found a large community of helminths and protozoans that were mostly restricted to the digestive tract and a few systemic parasites (e.g., Trypanosoma). Contrary to our expectations, all dendrobatid frogs regardless of the presence of alkaloid defenses have endoparasites, with their highest species richness located in the frog digestive tract. Some of these organisms (e.g., roundworms) might prove to be generalists, as they were not found to be co-diversifying with their frog hosts. We propose that endoparasites may escape poison frogs' chemical defenses by colonizing tissues with fewer alkaloids than the frog's skin, where most toxins are stored. Copyright © 2018 Elsevier Inc. All rights reserved.

Evasion and Immuno-Endocrine Regulation in Parasite Infection: Two Sides of the Same Coin in Chagas Disease?

PubMed

Morrot, Alexandre; Villar, Silvina R; González, Florencia B; Pérez, Ana R

2016-01-01

Chagas disease is a serious illness caused by the protozoan parasite Trypanosoma cruzi. Nearly 30% of chronically infected people develop cardiac, digestive, or mixed alterations, suggesting a broad range of host-parasite interactions that finally impact upon chronic disease outcome. The ability of T. cruzi to persist and cause pathology seems to depend on diverse factors like T. cruzi strains, the infective load and the route of infection, presence of virulence factors, the parasite capacity to avoid protective immune response, the strength and type of host defense mechanisms and the genetic background of the host. The host-parasite interaction is subject to a constant neuro-endocrine regulation that is thought to influence the adaptive immune system, and as the infection proceeds it can lead to a broad range of outcomes, ranging from pathogen elimination to its continued persistence in the host. In this context, T. cruzi evasion strategies and host defense mechanisms can be envisioned as two sides of the same coin, influencing parasite persistence and different outcomes observed in Chagas disease. Understanding how T. cruzi evade host's innate and adaptive immune response will provide important clues to better dissect mechanisms underlying the pathophysiology of Chagas disease.

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.

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

Mobile Genetic Elements and Evolution of CRISPR-Cas Systems: All the Way There and Back.

PubMed

Koonin, Eugene V; Makarova, Kira S

2017-10-01

The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-CRISPR-associated proteins (Cas) systems of bacterial and archaeal adaptive immunity show multifaceted evolutionary relationships with at least five classes of mobile genetic elements (MGE). First, the adaptation module of CRISPR-Cas that is responsible for the formation of the immune memory apparently evolved from a Casposon, a self-synthesizing transposon that employs the Cas1 protein as the integrase and might have brought additional cas genes to the emerging immunity loci. Second, a large subset of type III CRISPR-Cas systems recruited a reverse transcriptase from a Group II intron, providing for spacer acquisition from RNA. Third, effector nucleases of Class 2 CRISPR-Cas systems that are responsible for the recognition and cleavage of the target DNA were derived from transposon-encoded TnpB nucleases, most likely, on several independent occasions. Fourth, accessory nucleases in some variants of types I and III toxin and type VI effectors RNases appear to be ultimately derived from toxin nucleases of microbial toxin-antitoxin modules. Fifth, the opposite direction of evolution is manifested in the recruitment of CRISPR-Cas systems by a distinct family of Tn7-like transposons that probably exploit the capacity of CRISPR-Cas to recognize unique DNA sites to facilitate transposition as well as by bacteriophages that employ them to cope with host defense. Additionally, individual Cas proteins, such as the Cas4 nuclease, were recruited by bacteriophages and transposons. The two-sided evolutionary connection between CRISPR-Cas and MGE fits the "guns for hire" paradigm whereby homologous enzymatic machineries, in particular nucleases, are shuttled between MGE and defense systems and are used alternately as means of offense or defense. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2017. This work is written by US Government employees and is in the public domain in the US.

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

Distinct innate immune phagocyte responses to Aspergillus fumigatus conidia and hyphae in zebrafish larvae.

PubMed

Knox, Benjamin P; Deng, Qing; Rood, Mary; Eickhoff, Jens C; Keller, Nancy P; Huttenlocher, Anna

2014-10-01

Aspergillus fumigatus is the most common filamentous fungal pathogen of immunocompromised hosts, resulting in invasive aspergillosis (IA) and high mortality rates. Innate immunity is known to be the predominant host defense against A. fumigatus; however, innate phagocyte responses to A. fumigatus in an intact host and their contributions to host survival remain unclear. Here, we describe a larval zebrafish A. fumigatus infection model amenable to real-time imaging of host-fungal interactions in live animals. Following infection with A. fumigatus, innate phagocyte populations exhibit clear preferences for different fungal morphologies: macrophages rapidly phagocytose conidia and form aggregates around hyphae, while the neutrophil response is dependent upon the presence of hyphae. Depletion of macrophages rendered host larvae susceptible to invasive disease. Moreover, a zebrafish model of human leukocyte adhesion deficiency with impaired neutrophil function also resulted in invasive disease and impaired host survival. In contrast, macrophage-deficient but not neutrophil-deficient larvae exhibited attenuated disease following challenge with a less virulent (ΔlaeA) strain of A. fumigatus, which has defects in secondary metabolite production. Taking these results together, we have established a new vertebrate model for studying innate immune responses to A. fumigatus that reveals distinct roles for neutrophils and macrophages in mediating host defense against IA. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Use of OmpU porins for attachment and invasion of Crassostrea gigas immune cells by the oyster pathogen Vibrio splendidus

PubMed Central

Duperthuy, Marylise; Schmitt, Paulina; Garzón, Edwin; Caro, Audrey; Rosa, Rafael D.; Le Roux, Frédérique; Lautrédou-Audouy, Nicole; Got, Patrice; Romestand, Bernard; de Lorgeril, Julien; Kieffer-Jaquinod, Sylvie; Bachère, Evelyne; Destoumieux-Garzón, Delphine

2011-01-01

OmpU porins are increasingly recognized as key determinants of pathogenic host Vibrio interactions. Although mechanisms remain incompletely understood, various species, including the human pathogen Vibrio cholera, require OmpU for host colonization and virulence. We have shown previously that OmpU is essential for virulence in the oyster pathogen Vibrio splendidus LGP32. Here, we showed that V. splendidus LGP32 invades the oyster immune cells, the hemocytes, through subversion of host-cell actin cytoskeleton. In this process, OmpU serves as an adhesin/invasin required for β-integrin recognition and host cell invasion. Furthermore, the major protein of oyster plasma, the extracellular superoxide dismutase Cg-EcSOD, is used as an opsonin mediating the OmpU-promoted phagocytosis through its RGD sequence. Finally, the endocytosed bacteria were found to survive intracellularly, evading the host defense by preventing acidic vacuole formation and limiting reactive oxygen species production. We conclude that (i) V. splendidus is a facultative intracellular pathogen that manipulates host defense mechanisms to enter and survive in host immune cells, and (ii) that OmpU is a major determinant of host cell invasion in Vibrio species, used by V. splendidus LGP32 to attach and invade oyster hemocytes through opsonisation by the oyster plasma Cg-EcSOD. PMID:21282662

Phenotypic analysis of apoplastic effectors from the phytopathogenic nematode, Globodera rostochiensis demonstrates that an expansin can induce and suppress host defenses

USDA-ARS?s Scientific Manuscript database

The potato cyst nematode Globodera rostochiensis (Woll.) is an important pest of potato. Like other biotrophic pathogens, plant parasitic nematodes are presumed to employ effector proteins, secreted into the apoplast as well as the host cytoplasm to successfully infect their hosts. We have identifie...

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

TMV-Cg Coat Protein stabilizes DELLA proteins and in turn negatively modulates salicylic acid-mediated defense pathway during Arabidopsis thaliana viral infection.

PubMed

Rodriguez, Maria Cecilia; Conti, Gabriela; Zavallo, Diego; Manacorda, Carlos Augusto; Asurmendi, Sebastian

2014-08-03

Plant viral infections disturb defense regulatory networks during tissue invasion. Emerging evidence demonstrates that a significant proportion of these alterations are mediated by hormone imbalances. Although the DELLA proteins have been reported to be central players in hormone cross-talk, their role in the modulation of hormone signaling during virus infections remains unknown. This work revealed that TMV-Cg coat protein (CgCP) suppresses the salicylic acid (SA) signaling pathway without altering defense hormone SA or jasmonic acid (JA) levels in Arabidopsis thaliana. Furthermore, it was observed that the expression of CgCP reduces plant growth and delays the timing of floral transition. Quantitative RT-qPCR analysis of DELLA target genes showed that CgCP alters relative expression of several target genes, indicating that the DELLA proteins mediate transcriptional changes produced by CgCP expression. Analyses by fluorescence confocal microscopy showed that CgCP stabilizes DELLA proteins accumulation in the presence of gibberellic acid (GA) and that the DELLA proteins are also stabilized during TMV-Cg virus infections. Moreover, DELLA proteins negatively modulated defense transcript profiles during TMV-Cg infection. As a result, TMV-Cg accumulation was significantly reduced in the quadruple-DELLA mutant Arabidopsis plants compared to wild type plants. Taken together, these results demonstrate that CgCP negatively regulates the salicylic acid-mediated defense pathway by stabilizing the DELLA proteins during Arabidopsis thaliana viral infection, suggesting that CgCP alters the stability of DELLAs as a mechanism of negative modulation of antiviral defense responses.

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.

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

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.

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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

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

PubMed

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

2014-12-01

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

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

PubMed Central

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

2014-01-01

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

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.

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

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 in the patient tear. Negative regulators of these defense pathways were also found in patient tear indicating a fine balance between pathogen clearance and host tissue destruction during fungal infection depending upon the individual specific host - pathogen interaction. This understanding could be used to predict the progression and outcome of infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Caspase-12 and the inflammatory response to Yersinia pestis.

PubMed

Ferwerda, Bart; McCall, Matthew B B; de Vries, Maaike C; Hopman, Joost; Maiga, Boubacar; Dolo, Amagana; Doumbo, Ogobara; Daou, Modibo; de Jong, Dirk; Joosten, Leo A B; Tissingh, Rudi A; Reubsaet, Frans A G; Sauerwein, Robert; van der Meer, Jos W M; van der Ven, André J A M; Netea, Mihai G

2009-09-01

Caspase-12 functions as an antiinflammatory enzyme inhibiting caspase-1 and the NOD2/RIP2 pathways. Due to increased susceptibility to sepsis in individuals with functional caspase-12, an early-stop mutation leading to the loss of caspase-12 has replaced the ancient genotype in Eurasia and a significant proportion of individuals from African populations. In African-Americans, it has been shown that caspase-12 inhibits the pro-inflammatory cytokine production. We assessed whether similar mechanisms are present in African individuals, and whether evolutionary pressures due to plague may have led to the present caspase-12 genotype population frequencies. No difference in cytokine induction through the caspase-1 and/or NOD2/RIP2 pathways was observed in two independent African populations, among individuals with either an intact or absent caspase-12. In addition, stimulations with Yersinia pestis and two other species of Yersinia were preformed to investigate whether caspase-12 modulates the inflammatory reaction induced by Yersinia. We found that caspase-12 did not modulate cytokine production induced by Yersinia spp. Our experiments demonstrate for the first time the involvement of the NOD2/RIP2 pathway for recognition of Yersinia. However, caspase-12 does not modulate innate host defense against Y. pestis and alternative explanations for the geographical distribution of caspase-12 should be sought.

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.

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.

[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.

Loglines. November-December 2014

DTIC Science & Technology

2014-12-01

of Energy to our list of energy customers . And today, we store Department of Looking back over the past three years, I marvel at the colossal...supporting our host nation’s economies, something I know our customers appreciate. commands serve to remind us why DLA I’m very proud to wrap up my...worldwide and industry customers of DLA. Contents Defense or the Defense Logistics Agency. LOGLINES Official Flagship Publication of the Defense

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.

Myrosinase-dependent and –independent formation and control of isothiocyanate products of glucosinolate hydrolysis

USDA-ARS?s Scientific Manuscript database

Brassicales contain a myrosinase enzyme that hydrolyzes glucosinolates to form toxic isothiocyanates, as a defense against bacteria, fungi, insects and herbivores including man. Low levels of isothiocyanates trigger a host defense system in mammals that protects them against chronic diseases. Becaus...

32 CFR 634.6 - Requirements for driving privileges.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Section 634.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... in any state or host country. (2) Comply with laws and regulations governing motor vehicle operations... Vehicle Registration System (VRS). Vehicle registration is required on all Air Force and DLA installations...

32 CFR 634.6 - Requirements for driving privileges.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Section 634.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... in any state or host country. (2) Comply with laws and regulations governing motor vehicle operations... Vehicle Registration System (VRS). Vehicle registration is required on all Air Force and DLA installations...

32 CFR 634.6 - Requirements for driving privileges.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Section 634.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... in any state or host country. (2) Comply with laws and regulations governing motor vehicle operations... Vehicle Registration System (VRS). Vehicle registration is required on all Air Force and DLA installations...

32 CFR 634.6 - Requirements for driving privileges.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Section 634.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW... in any state or host country. (2) Comply with laws and regulations governing motor vehicle operations... Vehicle Registration System (VRS). Vehicle registration is required on all Air Force and DLA installations...

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 studies are reviewed here that reveal the interplay between peroxidase function and associated inorganic chemistry.

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

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.

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.

Geographical variation in parasitism shapes larval immune function in a phytophagous insect

NASA Astrophysics Data System (ADS)

Vogelweith, Fanny; Dourneau, Morgane; Thiéry, Denis; Moret, Yannick; Moreau, Jérôme

2013-12-01

Two of the central goals of immunoecology are to understand natural variation in the immune system among populations and to identify those selection pressures that shape immune traits. Maintenance of the immune system can be costly, and both food quality and parasitism selection pressure are factors potentially driving immunocompetence. In tritrophic interactions involving phytophagous insects, host plants, and natural enemies, the immunocompetence of phytophagous insects is constrained by selective forces from both the host plants and the natural enemies. Here, we assessed the roles of host plants and natural enemies as selective pressures on immune variation among natural populations of Lobesia botrana. Our results showed marked geographical variation in immune defenses and parasitism among different natural populations. Larval immune functions were dependent of the host plant quality and were positively correlated to parasitism, suggesting that parasitoids select for greater investment into immunity in moth. Furthermore, investment in immune defense was negatively correlated with body size, suggesting that it is metabolically expensive. The findings emphasize the roles of host plants and parasitoids as selective forces shaping host immune functions in natural conditions. We argue that kinds of study are central to understanding natural variations in immune functions, and the selective forces beyond.

Silicon Supplementation Alters the Composition of Herbivore Induced Plant Volatiles and Enhances Attraction of Parasitoids to Infested Rice Plants.

PubMed

Liu, Jian; Zhu, Jiwei; Zhang, Pengjun; Han, Liwei; Reynolds, Olivia L; Zeng, Rensen; Wu, Jinhong; Shao, Yue; You, Minsheng; Gurr, Geoff M

2017-01-01

Silicon (Si) is important in plant defenses that operate in a direct manner against herbivores, and work in rice ( Oryza sativa ) has established that this is mediated by the jasmonate signaling pathway. Plant defenses also operate indirectly, by the production of herbivore induced plant volatiles (HIPVs) that attract predators and parasitoids of herbivores. These indirect defenses too are mediated by the jasmonate pathway but no earlier work has demonstrated an effect of Si on HIPVs. In this study, we tested the effect of Si supplementation versus Si deprivation to rice plants on subsequent HIPV production following feeding by the important pest, rice leaffolder ( Cnaphalocrocis medinalis ). Gas chromatography-mass spectrometry analyses showed lower production of α-bergamotene, β-sesquiohellandrene, hexanal 2-ethyl, and cedrol from +Si herbivore-infested plants compared with -Si infested plants. These changes in plant chemistry were ecologically significant in altering the extent to which parasitoids were attracted to infested plants. Adult females of Trathala flavo-orbitalis and Microplitis mediator both exhibited greater attraction to the HIPV blend of +Si plants infested with their respective insect hosts compared to -Si infested plants. In equivalent studies using RNAi rice plants in which jasmonate perception was silenced there was no equivalent change to the HIPV blend associated with Si treatment; indicating that the effects of Si on HIPVs are modulated by the jasmonate pathway. Further, this work demonstrates that silicon alters the HIPV blend of herbivore-infested rice plants. The significance of this finding is that there are no earlier-published studies of this phenomenon in rice or any other plant species. Si treatment to crops offers scope for enhancing induced, indirect defenses and associated biological control of pests because parasitoids are more strongly attracted by the HIPVs produced by +Si plants.

Regulated nuclear trafficking of rpL10A mediated by NIK1 represents a defense strategy of plant cells against virus.

PubMed

Carvalho, Claudine M; Santos, Anésia A; Pires, Silvana R; Rocha, Carolina S; Saraiva, Daniela I; Machado, João Paulo B; Mattos, Eliciane C; Fietto, Luciano G; Fontes, Elizabeth P B

2008-12-01

The NSP-interacting kinase (NIK) receptor-mediated defense pathway has been identified recently as a virulence target of the geminivirus nuclear shuttle protein (NSP). However, the NIK1-NSP interaction does not fit into the elicitor-receptor model of resistance, and hence the molecular mechanism that links this antiviral response to receptor activation remains obscure. Here, we identified a ribosomal protein, rpL10A, as a specific partner and substrate of NIK1 that functions as an immediate downstream effector of NIK1-mediated response. Phosphorylation of cytosolic rpL10A by NIK1 redirects the protein to the nucleus where it may act to modulate viral infection. While ectopic expression of normal NIK1 or a hyperactive NIK1 mutant promotes the accumulation of phosphorylated rpL10A within the nuclei, an inactive NIK1 mutant fails to redirect the protein to the nuclei of co-transfected cells. Likewise, a mutant rpL10A defective for NIK1 phosphorylation is not redirected to the nucleus. Furthermore, loss of rpL10A function enhances susceptibility to geminivirus infection, resembling the phenotype of nik1 null alleles. We also provide evidence that geminivirus infection directly interferes with NIK1-mediated nuclear relocalization of rpL10A as a counterdefensive measure. However, the NIK1-mediated defense signaling neither activates RNA silencing nor promotes a hypersensitive response but inhibits plant growth and development. Although the virulence function of the particular geminivirus NSP studied here overcomes this layer of defense in Arabidopsis, the NIK1-mediated signaling response may be involved in restricting the host range of other viruses.

Contrasting Regulation of NO and ROS in Potato Defense-Associated Metabolism in Response to Pathogens of Different Lifestyles

PubMed Central

Floryszak-Wieczorek, Jolanta; Arasimowicz-Jelonek, Magdalena

2016-01-01

Our research provides new insights into how the low and steady-state levels of nitric oxide (NO) and reactive oxygen species (ROS) in potato leaves are altered after the challenge with the hemibiotroph Phytophthora infestans or the necrotroph Botrytis cinerea, with the subsequent rapid and invader-dependent modification of defense responses with opposite effects. Mainly in the avirulent (avr) P. infestans–potato system, NO well balanced with the superoxide level was tuned with a battery of SA-dependent defense genes, leading to the establishment of the hypersensitive response (HR) successfully arresting the pathogen. Relatively high levels of S-nitrosoglutathione and S-nitrosothiols concentrated in the main vein of potato leaves indicated the mobile function of these compounds as a reservoir of NO bioactivity. In contrast, low-level production of NO and ROS during virulent (vr) P. infestans-potato interactions might be crucial in the delayed up-regulation of PR-1 and PR-3 genes and compromised resistance to the hemibiotrophic pathogen. In turn, B. cinerea triggered huge NO overproduction and governed inhibition of superoxide production by blunting NADPH oxidase. Nevertheless, a relatively high level of H2O2 was found owing to the germin-like activity in cooperation with NO-mediated HR-like cell death in potato genotypes favorable to the necrotrophic pathogen. Moreover, B. cinerea not only provoked cell death, but also modulated the host redox milieu by boosting protein nitration, which attenuated SA production but not SA-dependent defense gene expression. Finally, based on obtained data the organismal cost of having machinery for HR in plant resistance to biotrophs is also discussed, while emphasizing new efforts to identify other components of the NO/ROS cell death pathway and improve plant protection against pathogens of different lifestyles. PMID:27695047

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.

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

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.

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.

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.

The ectromelia virus SPI-2 protein causes lethal mousepox by preventing NK cell responses.

PubMed

Melo-Silva, Carolina R; Tscharke, David C; Lobigs, Mario; Koskinen, Aulikki; Wong, Yik Chun; Buller, R Mark; Müllbacher, Arno; Regner, Matthias

2011-11-01

Ectromelia virus (ECTV) is a natural pathogen of mice that causes mousepox, and many of its genes have been implicated in the modulation of host immune responses. Serine protease inhibitor 2 (SPI-2) is one of these putative ECTV host response modifier proteins. SPI-2 is conserved across orthopoxviruses, but results defining its mechanism of action and in vivo function are lacking or contradictory. We studied the role of SPI-2 in mousepox by deleting the SPI-2 gene or its serine protease inhibitor reactive site. We found that SPI-2 does not affect viral replication or cell-intrinsic apoptosis pathways, since mutant viruses replicate in vitro as efficiently as wild-type virus. However, in the absence of SPI-2 protein, ECTV is attenuated in mousepox-susceptible mice, resulting in lower viral loads in the liver, decreased spleen pathology, and substantially improved host survival. This attenuation correlates with more effective immune responses in the absence of SPI-2, including an earlier serum gamma interferon (IFN-γ) response, raised serum interleukin 18 (IL-18), increased numbers of granzyme B(+) CD8(+) T cells, and, most notably, increased numbers and activation of NK cells. Both virus attenuation and the improved immune responses associated with SPI-2 deletion from ECTV are lost when mice are depleted of NK cells. Consequently, SPI-2 renders mousepox lethal in susceptible strains by preventing protective NK cell defenses.

Blufensin1 Negatively Impacts Basal Defense in Response to Barley Powdery Mildew

USDA-ARS?s Scientific Manuscript database

Plants have evolved complex regulatory mechanisms to control the defense response against microbial attack. Both temporal and spatial gene expression are tightly regulated in response to pathogen ingress, modulating both positive and negative control of defense. BLUFENSIN1 (BLN1), a small peptide ...

Silicon induced systemic defense responses in perennial ryegrass against Magnaporthe oryzae infection

USDA-ARS?s Scientific Manuscript database

Sustainable integrated disease management for gray leaf spot of perennial ryegrass may involve use of plant defense elicitors with compatible traditional fungicides to reduce disease incidence and severity. Silicon (Si) is a potential inducer or modulator of plant defenses against different pathogen...

Finding quasi-modules of human and viral miRNAs: a case study of human cytomegalovirus (HCMV)

PubMed Central

2012-01-01

Background MicroRNAs (miRNAs) are important regulators of gene expression encoded by a variety of organisms, including viruses. Although the function of most of the viral miRNAs is currently unknown, there is evidence that both viral and host miRNAs contribute to the interactions between viruses and their hosts. miRNAs constitute a complex combinatorial network, where one miRNA may target many genes and one gene may be targeted by multiple miRNAs. In particular, viral and host miRNAs may also have mutual target genes. Based on published evidence linking viral and host miRNAs there are three modes of mutual regulation: competing, cooperating, and compensating modes. Results In this paper we explore the compensating mode of mutual regulation upon Human Cytomegalovirus (HCMV) infection, when host miRNAs are down regulated and viral miRNAs compensate by mimicking their function. To achieve this, we develop a new algorithm which finds groups, called quasi-modules, of viral and host miRNAs and their mutual target genes, and use a new host miRNA expression data for HCMV-infected and uninfected cells. For two of the reported quasi-modules, supporting evidence from biological and medical literature is provided. Conclusions The modules found by our method may advance the understanding of the role of miRNAs in host-viral interactions, and the genes in these modules may serve as candidates for further experimental validation. PMID:23206407

The cytomegalovirus homolog of interleukin-10 requires phosphatidylinositol 3-kinase activity for inhibition of cytokine synthesis in monocytes.

PubMed

Spencer, Juliet V

2007-02-01

Human cytomegalovirus (CMV) has evolved numerous strategies for evading host immune defenses, including piracy of cellular cytokines. A viral homolog of interleukin-10, designated cmvIL-10, binds to the cellular IL-10 receptor and effects potent immune suppression. The signaling pathways employed by cmvIL-10 were investigated, and the classic IL-10R/JAK1/Stat3 pathway was found to be activated in monocytes. However, inhibition of JAK1 had little effect on cmvIL-10-mediated suppression of tumor necrosis factor alpha (TNF-alpha) production. Inhibition of the phosphatidylinositol 3-kinase/Akt pathway had a more significant impact on TNF-alpha levels but did not completely relieve the immune suppression, demonstrating that cmvIL-10 stimulates multiple signaling pathways to modulate cell function.

Modulation of inflammation and disease tolerance by DNA damage response pathways.

PubMed

Neves-Costa, Ana; Moita, Luis F

2017-03-01

The accurate replication and repair of DNA is central to organismal survival. This process is challenged by the many factors that can change genetic information such as replication errors and direct damage to the DNA molecule by chemical and physical agents. DNA damage can also result from microorganism invasion as an integral step of their life cycle or as collateral damage from host defense mechanisms against pathogens. Here we review the complex crosstalk of DNA damage response and immune response pathways that might be evolutionarily connected and argue that DNA damage response pathways can be explored therapeutically to induce disease tolerance through the activation of tissue damage control processes. Such approach may constitute the missing pillar in the treatment of critical illnesses caused by multiple organ failure, such as sepsis and septic shock. © 2016 Federation of European Biochemical Societies.

Lipid Rafts in Mast Cell Biology

PubMed Central

Silveira e Souza, Adriana Maria Mariano; Mazucato, Vivian Marino; Jamur, Maria Célia; Oliver, Constance

2011-01-01

Mast cells have long been recognized to have a direct and critical role in allergic and inflammatory reactions. In allergic diseases, these cells exert both local and systemic responses, including allergic rhinitis and anaphylaxis. Mast cell mediators are also related to many chronic inflammatory conditions. Besides the roles in pathological conditions, the biological functions of mast cells include roles in innate immunity, involvement in host defense mechanisms against parasites, immunomodulation of the immune system, tissue repair, and angiogenesis. Despite their growing significance in physiological and pathological conditions, much still remains to be learned about mast cell biology. This paper presents evidence that lipid rafts or raft components modulate many of the biological processes in mast cells, such as degranulation and endocytosis, play a role in mast cell development and recruitment, and contribute to the overall preservation of mast cell structure and organization. PMID:21490812

Manipulation of the Xanthophyll Cycle Increases Plant Susceptibility to Sclerotinia sclerotiorum.

PubMed

Zhou, Jun; Zeng, Lizhang; Liu, Jian; Xing, Da

2015-05-01

The xanthophyll cycle is involved in dissipating excess light energy to protect the photosynthetic apparatus in a process commonly assessed from non-photochemical quenching (NPQ) of chlorophyll fluorescence. Here, it is shown that the xanthophyll cycle is modulated by the necrotrophic pathogen Sclerotinia sclerotiorum at the early stage of infection. Incubation of Sclerotinia led to a localized increase in NPQ even at low light intensity. Further studies showed that this abnormal change in NPQ was closely correlated with a decreased pH caused by Sclerotinia-secreted oxalate, which might decrease the ATP synthase activity and lead to a deepening of thylakoid lumen acidification under continuous illumination. Furthermore, suppression (with dithiothreitol) or a defect (in the npq1-2 mutant) of violaxanthin de-epoxidase (VDE) abolished the Sclerotinia-induced NPQ increase. HPLC analysis showed that the Sclerotinia-inoculated tissue accumulated substantial quantities of zeaxanthin at the expense of violaxanthin, with a corresponding decrease in neoxanthin content. Immunoassays revealed that the decrease in these xanthophyll precursors reduced de novo abscisic acid (ABA) biosynthesis and apparently weakened tissue defense responses, including ROS induction and callose deposition, resulting in enhanced plant susceptibility to Sclerotinia. We thus propose that Sclerotinia antagonizes ABA biosynthesis to suppress host defense by manipulating the xanthophyll cycle in early pathogenesis. These findings provide a model of how photoprotective metabolites integrate into the defense responses, and expand the current knowledge of early plant-Sclerotinia interactions at infection sites.

Induced Genome-Wide Binding of Three Arabidopsis WRKY Transcription Factors during Early MAMP-Triggered Immunity.

PubMed

Birkenbihl, Rainer P; Kracher, Barbara; Somssich, Imre E

2017-01-01

During microbial-associated molecular pattern-triggered immunity (MTI), molecules derived from microbes are perceived by cell surface receptors and upon signaling to the nucleus initiate a massive transcriptional reprogramming critical to mount an appropriate host defense response. WRKY transcription factors play an important role in regulating these transcriptional processes. Here, we determined on a genome-wide scale the flg22-induced in vivo DNA binding dynamics of three of the most prominent WRKY factors, WRKY18, WRKY40, and WRKY33. The three WRKY factors each bound to more than 1000 gene loci predominantly at W-box elements, the known WRKY binding motif. Binding occurred mainly in the 500-bp promoter regions of these genes. Many of the targeted genes are involved in signal perception and transduction not only during MTI but also upon damage-associated molecular pattern-triggered immunity, providing a mechanistic link between these functionally interconnected basal defense pathways. Among the additional targets were genes involved in the production of indolic secondary metabolites and in modulating distinct plant hormone pathways. Importantly, among the targeted genes were numerous transcription factors, encoding predominantly ethylene response factors, active during early MTI, and WRKY factors, supporting the previously hypothesized existence of a WRKY subregulatory network. Transcriptional analysis revealed that WRKY18 and WRKY40 function redundantly as negative regulators of flg22-induced genes often to prevent exaggerated defense responses. © 2016 American Society of Plant Biologists. All rights reserved.

Manipulation of the Xanthophyll Cycle Increases Plant Susceptibility to Sclerotinia sclerotiorum

PubMed Central

Zhou, Jun; Zeng, Lizhang; Liu, Jian; Xing, Da

2015-01-01

The xanthophyll cycle is involved in dissipating excess light energy to protect the photosynthetic apparatus in a process commonly assessed from non-photochemical quenching (NPQ) of chlorophyll fluorescence. Here, it is shown that the xanthophyll cycle is modulated by the necrotrophic pathogen Sclerotinia sclerotiorum at the early stage of infection. Incubation of Sclerotinia led to a localized increase in NPQ even at low light intensity. Further studies showed that this abnormal change in NPQ was closely correlated with a decreased pH caused by Sclerotinia-secreted oxalate, which might decrease the ATP synthase activity and lead to a deepening of thylakoid lumen acidification under continuous illumination. Furthermore, suppression (with dithiothreitol) or a defect (in the npq1-2 mutant) of violaxanthin de-epoxidase (VDE) abolished the Sclerotinia-induced NPQ increase. HPLC analysis showed that the Sclerotinia-inoculated tissue accumulated substantial quantities of zeaxanthin at the expense of violaxanthin, with a corresponding decrease in neoxanthin content. Immunoassays revealed that the decrease in these xanthophyll precursors reduced de novo abscisic acid (ABA) biosynthesis and apparently weakened tissue defense responses, including ROS induction and callose deposition, resulting in enhanced plant susceptibility to Sclerotinia. We thus propose that Sclerotinia antagonizes ABA biosynthesis to suppress host defense by manipulating the xanthophyll cycle in early pathogenesis. These findings provide a model of how photoprotective metabolites integrate into the defense responses, and expand the current knowledge of early plant-Sclerotinia interactions at infection sites. PMID:25993128

Attenuation of virulence in pathogenic bacteria using synthetic quorum-sensing modulators under native conditions on plant hosts

PubMed Central

Palmer, Andrew G.; Streng, Evan; Blackwell, Helen E.

2011-01-01

Quorum sensing (QS) is often critical in both pathogenic and mutualistic relationships between bacteria and their eukaryotic hosts. Gram-negative bacteria typically use N-acylated L-homoserine lactone (AHL) signals for QS. We have identified a number of synthetic AHL analogues that are able to strongly modulate QS in culture-based, reporter gene assays. While informative, these assays represent idealized systems and their relevance to QS under native conditions is often unclear. As one of our goals is to utilize synthetic QS modulators to study bacterial communication under native conditions, identifying robust host-bacteria model systems for their evaluation is crucial. We reasoned that the host-pathogen interaction between Solanum tuberosum (potato) and the Gram-negative pathogen Pectobacterium carotovora would be ideal for such studies as we have identified several potent, synthetic QS modulators for this pathogen, and infection assays in potato are facile. Herein, we report on our development of this host-pathogen system, and another in Phaseolus vulgaris (green bean), as a means for monitoring the ability of abiotic AHLs to modulate QS-regulated virulence in host infection assays. Our assays confirmed that QS modulators previously identified through culture-based assays largely retained their activity profiles when introduced into the plant host. However, inhibition of virulence in wild-type infections was highly dependent on the timing of compound dosing. This study is the first to demonstrate that our AHL analogs are active in wild-type bacteria in their native eukaryotic hosts, and provides compelling evidence for the application of these molecules as probes to study QS in a range of organisms and environments. PMID:21932837

Evasion and Immuno-Endocrine Regulation in Parasite Infection: Two Sides of the Same Coin in Chagas Disease?

PubMed Central

Morrot, Alexandre; Villar, Silvina R.; González, Florencia B.; Pérez, Ana R.

2016-01-01

Chagas disease is a serious illness caused by the protozoan parasite Trypanosoma cruzi. Nearly 30% of chronically infected people develop cardiac, digestive, or mixed alterations, suggesting a broad range of host-parasite interactions that finally impact upon chronic disease outcome. The ability of T. cruzi to persist and cause pathology seems to depend on diverse factors like T. cruzi strains, the infective load and the route of infection, presence of virulence factors, the parasite capacity to avoid protective immune response, the strength and type of host defense mechanisms and the genetic background of the host. The host-parasite interaction is subject to a constant neuro-endocrine regulation that is thought to influence the adaptive immune system, and as the infection proceeds it can lead to a broad range of outcomes, ranging from pathogen elimination to its continued persistence in the host. In this context, T. cruzi evasion strategies and host defense mechanisms can be envisioned as two sides of the same coin, influencing parasite persistence and different outcomes observed in Chagas disease. Understanding how T. cruzi evade host's innate and adaptive immune response will provide important clues to better dissect mechanisms underlying the pathophysiology of Chagas disease. PMID:27242726

Diverse amino acid changes at specific positions in the N-terminal region of the coat protein allow Plum pox virus to adapt to new hosts.

PubMed

Carbonell, Alberto; Maliogka, Varvara I; Pérez, José de Jesús; Salvador, Beatriz; León, David San; García, Juan Antonio; Simón-Mateo, Carmen

2013-10-01

Plum pox virus (PPV)-D and PPV-R are two isolates from strain D of PPV that differ in host specificity. Previous analyses of chimeras originating from PPV-R and PPV-D suggested that the N terminus of the coat protein (CP) includes host-specific pathogenicity determinants. Here, these determinants were mapped precisely by analyzing the infectivity in herbaceous and woody species of chimeras containing a fragment of the 3' region of PPV-D (including the region coding for the CP) in a PPV-R backbone. These chimeras were not infectious in Prunus persica, but systemically infected Nicotiana clevelandii and N. benthamiana when specific amino acids were modified or deleted in a short 30-amino-acid region of the N terminus of the CP. Most of these mutations did not reduce PPV fitness in Prunus spp. although others impaired systemic infection in this host. We propose a model in which the N terminus of the CP, highly relevant for virus systemic movement, is targeted by a host defense mechanism in Nicotiana spp. Mutations in this short region allow PPV to overcome the defense response in this host but can compromise the efficiency of PPV systemic movement in other hosts such as Prunus spp.

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.

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

Direct and indirect plant defenses are not suppressed by endosymbionts of a specialist root herbivore

USDA-ARS?s Scientific Manuscript database

Insect endosymbionts influence many important metabolic and developmental processes of their host. It has been speculated that they may also help to manipulate and suppress plant defenses to the benefit of herbivores. Recently, endosymbionts of the root herbivore Diabrotica virgifera virgifera have ...

32 CFR 809a.11 - Procedures outside the United States.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Intervention by United States military personnel outside the United States is governed by international law, bilateral and other international agreements to which the United States is a party, and host-nation laws... Section 809a.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE...

32 CFR 809a.11 - Procedures outside the United States.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Intervention by United States military personnel outside the United States is governed by international law, bilateral and other international agreements to which the United States is a party, and host-nation laws... Section 809a.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE...

32 CFR 809a.11 - Procedures outside the United States.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... Intervention by United States military personnel outside the United States is governed by international law, bilateral and other international agreements to which the United States is a party, and host-nation laws... Section 809a.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE...

32 CFR 809a.11 - Procedures outside the United States.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... Intervention by United States military personnel outside the United States is governed by international law, bilateral and other international agreements to which the United States is a party, and host-nation laws... Section 809a.11 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE...

32 CFR 634.43 - Driving records.

Code of Federal Regulations, 2011 CFR

2011-07-01

... intoxicating liquor (0.08% or greater on DOD installations; violation of civil law off post). C. Driving a... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL... the same as the date of civil conviction, or the date that State or host-nation driving privileges are...

32 CFR 634.43 - Driving records.

Code of Federal Regulations, 2014 CFR

2014-07-01

... intoxicating liquor (0.08% or greater on DOD installations; violation of civil law off post). C. Driving a... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL... the same as the date of civil conviction, or the date that State or host-nation driving privileges are...

32 CFR 634.43 - Driving records.

Code of Federal Regulations, 2012 CFR

2012-07-01

... intoxicating liquor (0.08% or greater on DOD installations; violation of civil law off post). C. Driving a... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL... the same as the date of civil conviction, or the date that State or host-nation driving privileges are...

32 CFR 634.43 - Driving records.

Code of Federal Regulations, 2013 CFR

2013-07-01

... intoxicating liquor (0.08% or greater on DOD installations; violation of civil law off post). C. Driving a... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) LAW ENFORCEMENT AND CRIMINAL... the same as the date of civil conviction, or the date that State or host-nation driving privileges are...

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.

A eukaryotic-acquired gene by a biotrophic phytopathogen allows prolonged survival on the host by counteracting the shut-down of plant photosynthesis.

PubMed

Garavaglia, Betiana S; Thomas, Ludivine; Gottig, Natalia; Dunger, Germán; Garofalo, Cecilia G; Daurelio, Lucas D; Ndimba, Bongani; Orellano, Elena G; Gehring, Chris; Ottado, Jorgelina

2010-01-28

Xanthomonas citri pv. citri, the bacteria responsible for citrus canker posses a biological active plant natriuretic peptide (PNP)-like protein, not present in any other bacteria. PNPs are a class of extracellular, systemically mobile peptides that elicit a number of plant responses important in homeostasis and growth. Previously, we showed that a Xanthomonas citri pv. citri mutant lacking the PNP-like protein XacPNP produced more necrotic lesions in citrus leaves than wild type infections and suggested a role for XacPNP in the regulation of host homeostasis. Here we have analyzed the proteome modifications observed in citrus leaves infected with the wild type and XacPNP deletion mutant bacteria. While both of them cause down-regulation of enzymes related to photosynthesis as well as chloroplastic ribosomal proteins, proteins related to defense responses are up-regulated. However, leaves infiltrated with the XacPNP deletion mutant show a more pronounced decrease in photosynthetic proteins while no reduction in defense related proteins as compared to the wild-type pathogen. This suggests that XacPNP serves the pathogen to maintain host photosynthetic efficiency during pathogenesis. The results from the proteomics analyses are consistent with our chlorophyll fluorescence data and transcript analyses of defense genes that show a more marked reduction in photosynthesis in the mutant but no difference in the induction of genes diagnostic for biotic-stress responses. We therefore conclude that XacPNP counteracts the shut-down of host photosynthesis during infection and in that way maintains the tissue in better conditions, suggesting that the pathogen has adapted a host gene to modify its natural host and render it a better reservoir for prolonged bacterial survival and thus for further colonization.

Molecular constituents of the extracellular matrix in rat liver mounting a hepatic progenitor cell response for tissue repair

PubMed Central

2013-01-01

Background Tissue repair in the adult mammalian liver occurs in two distinct processes, referred to as the first and second tiers of defense. We undertook to characterize the changes in molecular constituents of the extracellular matrix when hepatic progenitor cells (HPCs) respond in a second tier of defense to liver injury. Results We used transcriptional profiling on rat livers responding by a first tier (surgical removal of 70% of the liver mass (PHx protocol)) and a second tier (70% hepatectomy combined with exposure to 2-acetylaminofluorene (AAF/PHx protocol)) of defense to liver injury and compared the transcriptional signatures in untreated rat liver (control) with those from livers of day 1, day 5 and day 9 post hepatectomy in both protocols. Numerous transcripts encoding specific subunits of collagens, laminins, integrins, and various other extracellular matrix structural components were differentially up- or down-modulated (P < 0.01). The levels of a number of transcripts were significantly up-modulated, mainly in the second tier of defense (Agrn, Bgn, Fbn1, Col4a1, Col8a1, Col9a3, Lama5, Lamb1, Lamb2, Itga4, Igtb2, Itgb4, Itgb6, Nid2), and their signal intensities showed a strong or very strong correlation with Krt1-19, a well-established marker of a ductular/HPC reaction. Furthermore, a significant up-modulation and very strong correlation between the transcriptional profiles of Krt1-19 and St14 encoding matriptase, a component of a novel protease system, was found in the second tier of defense. Real-time PCR confirmed the modulation of St14 transcript levels and strong correlation to Krt-19 and also showed a significant up-modulation and strong correlation to Spint1 encoding HAI-1, a cognate inhibitor of matriptase. Immunodetection and three-dimensional reconstructions showed that laminin, Collagen1a1, agrin and nidogen1 surrounded bile ducts, proliferating cholangiocytes, and HPCs in ductular reactions regardless of the nature of defense. Similarly, matriptase and HAI-1 were expressed in cholangiocytes regardless of the tier of defense, but in the second tier of defense, a subpopulation of HPCs in ductular reactions co-expressed HAI-1 and the fetal hepatocyte marker Dlk1. Conclusion Transcriptional profiling and immunodetection, including three-dimensional reconstruction, generated a detailed overview of the extracellular matrix constituents expressed in a second tier of defense to liver injury. PMID:24359594

Host discrimination in modular mutualisms: a theoretical framework for meta-populations of mutualists and exploiters

PubMed Central

Steidinger, Brian S.; Bever, James D.

2016-01-01

Plants in multiple symbioses are exploited by symbionts that consume their resources without providing services. Discriminating hosts are thought to stabilize mutualism by preferentially allocating resources into anatomical structures (modules) where services are generated, with examples of modules including the entire inflorescences of figs and the root nodules of legumes. Modules are often colonized by multiple symbiotic partners, such that exploiters that co-occur with mutualists within mixed modules can share rewards generated by their mutualist competitors. We developed a meta-population model to answer how the population dynamics of mutualists and exploiters change when they interact with hosts with different module occupancies (number of colonists per module) and functionally different patterns of allocation into mixed modules. We find that as module occupancy increases, hosts must increase the magnitude of preferentially allocated resources in order to sustain comparable populations of mutualists. Further, we find that mixed colonization can result in the coexistence of mutualist and exploiter partners, but only when preferential allocation follows a saturating function of the number of mutualists in a module. Finally, using published data from the fig–wasp mutualism as an illustrative example, we derive model predictions that approximate the proportion of exploiter, non-pollinating wasps observed in the field. PMID:26740613

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

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.

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.

Worming Their Way into the Picture: Microbiota Help Helminths Modulate Host Immunity.

PubMed

Reynolds, Lisa A; Finlay, B Brett

2015-11-17

Parasitic helminths are potent regulators of host immunity, including inhibition of allergic inflammation. In this issue of Immunity, Zaiss et al. (2015) reveal that microbiota compositional shifts during helminth infection contribute to the multifaceted ways that helminths modulate host immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

Pseudomonas syringae Type III Effector HopBB1 Promotes Host Transcriptional Repressor Degradation to Regulate Phytohormone Responses and Virulence.

PubMed

Yang, Li; Teixeira, Paulo José Pereira Lima; Biswas, Surojit; Finkel, Omri M; He, Yijian; Salas-Gonzalez, Isai; English, Marie E; Epple, Petra; Mieczkowski, Piotr; Dangl, Jeffery L

2017-02-08

Independently evolved pathogen effectors from three branches of life (ascomycete, eubacteria, and oomycete) converge onto the Arabidopsis TCP14 transcription factor to manipulate host defense. However, the mechanistic basis for defense control via TCP14 regulation is unknown. We demonstrate that TCP14 regulates the plant immune system by transcriptionally repressing a subset of the jasmonic acid (JA) hormone signaling outputs. A previously unstudied Pseudomonas syringae (Psy) type III effector, HopBB1, interacts with TCP14 and targets it to the SCF COI1 degradation complex by connecting it to the JA signaling repressor JAZ3. Consequently, HopBB1 de-represses the TCP14-regulated subset of JA response genes and promotes pathogen virulence. Thus, HopBB1 fine-tunes host phytohormone crosstalk by precisely manipulating part of the JA regulon to avoid pleiotropic host responses while promoting pathogen proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular and genomic characterization of pathogenic traits of group A Streptococcus pyogenes

PubMed Central

HAMADA, Shigeyuki; KAWABATA, Shigetada; NAKAGAWA, Ichiro

2015-01-01

Group A streptococcus (GAS) or Streptococcus pyogenes causes various diseases ranging from self-limiting sore throat to deadly invasive diseases. The genome size of GAS is 1.85–1.9 Mb, and genomic rearrangement has been demonstrated. GAS possesses various surface-associated substances such as hyaluronic capsule, M proteins, and fibronectin/laminin/immunoglobulin-binding proteins. These are related to the virulence and play multifaceted and mutually reflected roles in the pathogenesis of GAS infections. Invasion of GAS into epithelial cells and deeper tissues provokes immune and non-immune defense or inflammatory responses including the recruitment of neutrophils, macrophages, and dendritic cells in hosts. GAS frequently evades host defense mechanisms by using its virulence factors. Extracellular products of GAS may perturb cellular and subcellular functions and degrade tissues enzymatically, which leads to the aggravation of local and/or systemic disorders in the host. In this review, we summarize some important cellular and extracellular substances that may affect pathogenic processes during GAS infections, and the host responses to these. PMID:26666305

Apicomplexans pulling the strings: manipulation of the host cell cytoskeleton dynamics.

PubMed

Cardoso, Rita; Soares, Helena; Hemphill, Andrew; Leitão, Alexandre

2016-07-01

Invasive stages of apicomplexan parasites require a host cell to survive, proliferate and advance to the next life cycle stage. Once invasion is achieved, apicomplexans interact closely with the host cell cytoskeleton, but in many cases the different species have evolved distinct mechanisms and pathways to modulate the structural organization of cytoskeletal filaments. The host cell cytoskeleton is a complex network, largely, but not exclusively, composed of microtubules, actin microfilaments and intermediate filaments, all of which are modulated by associated proteins, and it is involved in diverse functions including maintenance of cell morphology and mechanical support, migration, signal transduction, nutrient uptake, membrane and organelle trafficking and cell division. The ability of apicomplexans to modulate the cytoskeleton to their own advantage is clearly beneficial. We here review different aspects of the interactions of apicomplexans with the three main cytoskeletal filament types, provide information on the currently known parasite effector proteins and respective host cell targets involved, and how these interactions modulate the host cell physiology. Some of these findings could provide novel targets that could be exploited for the development of preventive and/or therapeutic strategies.

Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens

DTIC Science & Technology

2005-07-01

AD Award Number: W81XWH-04-1-0668 TITLE: Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens PRINCIPAL INVESTIGATOR: Richard T...AND SUBTITLE 5a. CONTRACT NUMBER Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens 5b. GRANT NUMBER W81XWH-04-!1-0668 5c...neu-N mice can be readily applied to clinical trial development. The goal of the present work is to test the hypothesis that reproductive hormones can

Identification of Biomarkers for Defense Response to Plasmopara viticola in a Resistant Grape Variety.

PubMed

Chitarrini, Giulia; Soini, Evelyn; Riccadonna, Samantha; Franceschi, Pietro; Zulini, Luca; Masuero, Domenico; Vecchione, Antonella; Stefanini, Marco; Di Gaspero, Gabriele; Mattivi, Fulvio; Vrhovsek, Urska

2017-01-01

Downy mildew ( Plasmopara viticola ) is one of the most destructive diseases of the cultivated species Vitis vinifera . The use of resistant varieties, originally derived from backcrosses of North American Vitis spp., is a promising solution to reduce disease damage in the vineyards. To shed light on the type and the timing of pathogen-triggered resistance, this work aimed at discovering biomarkers for the defense response in the resistant variety Bianca, using leaf discs after inoculation with a suspension of P. viticola . We investigated primary and secondary metabolism at 12, 24, 48, and 96 h post-inoculation (hpi). We used methods of identification and quantification for lipids (LC-MS/MS), phenols (LC-MS/MS), primary compounds (GC-MS), and semi-quantification for volatile compounds (GC-MS). We were able to identify and quantify or semi-quantify 176 metabolites, among which 53 were modulated in response to pathogen infection. The earliest changes occurred in primary metabolism at 24-48 hpi and involved lipid compounds, specifically unsaturated fatty acid and ceramide; amino acids, in particular proline; and some acids and sugars. At 48 hpi, we also found changes in volatile compounds and accumulation of benzaldehyde, a promoter of salicylic acid-mediated defense. Secondary metabolism was strongly induced only at later stages. The classes of compounds that increased at 96 hpi included phenylpropanoids, flavonols, stilbenes, and stilbenoids. Among stilbenoids we found an accumulation of ampelopsin H + vaticanol C, pallidol, ampelopsin D + quadrangularin A, Z -miyabenol C, and α-viniferin in inoculated samples. Some of these compounds are known as phytoalexins, while others are novel biomarkers for the defense response in Bianca. This work highlighted some important aspects of the host response to P. viticola in a commercial variety under controlled conditions, providing biomarkers for a better understanding of the mechanism of plant defense and a potential application in field studies of resistant varieties.

Functional genomic responses to cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR(delta508) in the lung.

PubMed

Xu, Yan; Liu, Cong; Clark, Jean C; Whitsett, Jeffrey A

2006-04-21

Cystic fibrosis (CF), a common lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) that disturbs fluid homeostasis and host defense in target organs. The effects of CFTR and delta508-CFTR were assessed in transgenic mice that 1) lack CFTR expression (Cftr-/-); 2) express the human delta508 CFTR (CFTR(delta508)); 3) overexpress the normal human CFTR (CFTR(tg)) in respiratory epithelial cells. Genes were selected from Affymetrix Murine Gene-Chips analysis and subjected to functional classification, k-means clustering, promoter cis-elements/modules searching, literature mining, and pathway exploring. Genomic responses to Cftr-/- were not corrected by expression of CFTR(delta508). Genes regulating host defense, inflammation, fluid and electrolyte transport were similarly altered in Cftr-/- and CFTR(delta508) mice. CFTR(delta508) induced a primary disturbance in expression of genes regulating redox and antioxidant systems. Genomic responses to CFTR(tg) were modest and were not associated with lung pathology. CFTR(tg) and CFTR(delta508) induced genes encoding heat shock proteins and other chaperones but did not activate the endoplasmic reticulum-associated degradation pathway. RNAs encoding proteins that directly interact with CFTR were identified in each of the CFTR mouse models, supporting the hypothesis that CFTR functions within a multiprotein complex whose members interact at the level of protein-protein interactions and gene expression. Promoters of genes influenced by CFTR shared common regulatory elements, suggesting that their co-expression may be mediated by shared regulatory mechanisms. Genes and pathways involved in the response to CFTR may be of interest as modifiers of CF.

Immune Modulating Topical S100A8/A9 Inhibits Growth of Pseudomonas aeruginosa and Mitigates Biofilm Infection in Chronic Wounds.

PubMed

Trøstrup, Hannah; Lerche, Christian Johann; Christophersen, Lars; Jensen, Peter Østrup; Høiby, Niels; Moser, Claus

2017-06-26

Pseudomonas aeruginosa biofilm maintains and perturbs local host defense, hindering timely wound healing. Previously, we showed that P. aeruginosa suppressed S100A8/A9 of the murine innate host defense. We assessed the potential antimicrobial effect of S100A8/A9 on biofilm-infected wounds in a murine model and P. aeruginosa growth in vitro. Seventy-six mice, inflicted with a full-thickness burn wound were challenged subcutaneously (s.c.) by 10⁶ colony-forming units (CFUs) of P. aeruginosa biofilm. Mice were subsequently randomized into two treatment groups, one group receiving recombinant murine S100A8/A9 and a group of vehicle controls (phosphate-buffered saline, PBS) all treated with s.c. injections daily for up to five days. Wounds were analyzed for quantitative bacteriology and contents of key inflammatory markers. Count of blood polymorphonuclear leukocytes was included. S100A8/A9-treatment ameliorated wound infection, as evaluated by quantitative bacteriology ( p ≤ 0.05). In vitro, growth of P. aeruginosa was inhibited dose-dependently by S100A8/A9 in concentrations from 5 to 40 μg/mL, as determined by optical density-measurement (OD-measurement) and quantitative bacteriology. Treatment slightly augmented key inflammatory cytokine Tumor Necrosis Factor-α (TNF-α), but dampened interferon-γ (IFN-γ) levels and blood polymorphonuclear count. In conclusion, topical S100A8/A9 displays remarkable novel immune stimulatory and anti-infective properties in vivo and in vitro. Importantly, treatment by S100A8/A9 provides local infection control. Implications for a role as adjunctive treatment in healing of chronic biofilm-infected wounds are discussed.

Norcantharidin Facilitates LPS-Mediated Immune Responses by Up-Regulation of AKT/NF-κB Signaling in Macrophages

PubMed Central

Li, Ruimei; Tan, Binghe; Han, Honghui; Liu, Mingyao; Qian, Min; Du, Bing

2012-01-01

Norcantharidin (NCTD), a demethylated analog of cantharidin, is a common used clinical drug to inhibit proliferation and metastasis of cancer cells. But the role of NCTD in modulating immune responses remains unknown. Here, we investigated the function and mechanism of NCTD in regulation of TLR4 associated immune response in macrophages. We evaluated the influence of NCTD on host defense against invaded pathogens by acute peritonitis mouse model, ELISA, Q-PCR, nitrite quantification, phagocytosis assay and gelatin zymography assay. Our data showed that the survival and the serum concentrations of IL-6 and TNF-α were all enhanced by NCTD significantly in peritonitis mouse model. Accordingly, LPS-induced cytokine, nitric oxide and MMP-9 production as well as the phagocytosis of bacteria were all up-regulated by NCTD in a dose dependent manner in both RAW264.7 cells and bone marrow-derived macrophages (BMMs). Then we further analyzed TLR4 associated signaling pathway by Western blot, Immunofluorescence and EMSA in the presence or absence of LPS. The phosphorylation of AKT and p65 at serine 536 but not serine 468 was enhanced obviously by NCTD in a dose dependent manner, whereas the degradation of IκBα was little effected. Consequently, the nuclear translocation and DNA binding ability of NF-κB was also increased by NCTD obviously in RAW264.7 cells. Our results demonstrated that NCTD could facilitate LPS-mediated immune response through promoting the phosphorylation of AKT/p65 and transcriptional activity of NF-κB, thus reprofiling the traditional anti-tumor drug NCTD as a novel immune regulator in promoting host defense against bacterial infection. PMID:22984593

Antimicrobial and immunomodulatory activity of host defense peptides, clavanins and LL-37, in vitro: An endodontic perspective.

PubMed

Lima, Stella Maris F; Freire, Mirna S; Gomes, Ana Luisa O; Cantuária, Ana Paula C; Dutra, Flávia Rodrigues P; Magalhães, Beatriz S; Sousa, Maurício Gonçalves C; Migliolo, Ludovico; Almeida, Jeeser A; Franco, Octávio L; Rezende, Taia Maria B

2017-09-01

Endodontic treatment is mainly based on root canal disinfection and its failure may be motivated by microbial resistance. Endodontic therapy can be benefitted by host defense peptides (HDPs), which are multifunctional molecules that act against persistent infection and inflammation. This study aimed to evaluate the antimicrobial, cytotoxic and immunomodulatory activity of several HDPs, namely clavanin A, clavanin A modified (MO) and LL-37, compared to intracanal medication Ca(OH) 2 . HDPs and Ca(OH) 2 were evaluated by: (1) antimicrobial assays against Candida albicans and Enterococcus faecalis, (2) cytotoxicity assays and (3) cytokine tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-1α, IL-6, IL-10 and IL-12 and nitric oxide (NO) production by RAW 264.7 cells incubated with or without heat-killed (HK) C. albicans or E. faecalis combined or not with interferon-γ. The minimum inhibitory concentration (MIC) was established only for E. faecalis (LL-37, 57μM). Considering cytotoxicity, clavanin MO was able to reduce cell viability in many groups and demonstrated lowest LC 50 . The Ca(OH) 2 up-regulated the production of MCP-1, TNF-α, IL-12 and IL-6 and down-regulated IL-1α, IL-10 and NO. Clavanins up-regulated the TNF-α and NO and down-regulated IL-10 production. LL-37 demonstrated up-regulation of IL-6 and TNF-α production and down-regulation in IL-10 and NO production. In conclusion, LL-37 demonstrated better antibacterial potential. In addition, Ca(OH) 2 demonstrated a proinflammatory response, while the HDPs modulated the inflammatory response from non-interference with the active cytokines in the osteoclastogenesis process, probably promoting the health of periradicular tissues. Copyright © 2017 Elsevier Inc. All rights reserved.

Salmonella Enterica Serovar Typhimurium BipA Exhibits Two Distinct Ribosome Binding Modes

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

deLivron, M.; Robinson, V

BipA is a highly conserved prokaryotic GTPase that functions to influence numerous cellular processes in bacteria. In Escherichia coli and Salmonella enterica serovar Typhimurium, BipA has been implicated in controlling bacterial motility, modulating attachment and effacement processes, and upregulating the expression of virulence genes and is also responsible for avoidance of host defense mechanisms. In addition, BipA is thought to be involved in bacterial stress responses, such as those associated with virulence, temperature, and symbiosis. Thus, BipA is necessary for securing bacterial survival and successful invasion of the host. Steady-state kinetic analysis and pelleting assays were used to assess themore » GTPase and ribosome-binding properties of S. enterica BipA. Under normal bacterial growth, BipA associates with the ribosome in the GTP-bound state. However, using sucrose density gradients, we demonstrate that the association of BipA and the ribosome is altered under stress conditions in bacteria similar to those experienced during virulence. The data show that this differential binding is brought about by the presence of ppGpp, an alarmone that signals the onset of stress-related events in bacteria.« less

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.

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

Vaccinia Virus C9 Ankyrin Repeat/F-Box Protein Is a Newly Identified Antagonist of the Type I Interferon-Induced Antiviral State.

PubMed

Liu, Ruikang; Moss, Bernard

2018-05-01

Type I interferons (IFNs) induce expression of more than 300 cellular genes that provide protection against viruses and other pathogens. For survival, viruses evolved defenses to prevent the IFN response or counteract the IFN-induced antiviral state. However, because viruses and cells coevolved, the dynamic relationship between virus and host is difficult to discern. In the present study, we demonstrated that vaccinia virus with a large deletion near the left end of the genome had a diminished ability to replicate in cells that had been pretreated with beta interferon (IFN-β), suggesting that one or more of the missing 17 open reading frames (ORFs) encode an antagonist of the IFN-induced antiviral state. By systematically deleting groups of ORFs and then individual ORFs, the C9L gene was shown to be required for IFN resistance. Replication of the C9L deletion mutant (vΔC9) was impaired in human cells that had been pretreated with IFN-β. Expression of viral early genes occurred, but subsequent events, including genome uncoating, genome replication, and postreplicative gene expression, were inhibited. Expression of the C9 protein occurred prior to genome replication, consistent with an early role in counteracting the IFN-induced antiviral state. C9 contains six ankyrin repeat motifs and a near C-terminal F-box. Mass spectrometry and immunoblotting identified host proteins that copurified with a functional epitope-tagged C9. The most abundant proteins were components of the SCF (CUL1, SKP1, F-box) and signalosome/deneddylation complexes, which interact with each other, suggesting a possible role in proteolysis of one or more interferon-induced proteins. IMPORTANCE Poxviruses comprise a family of large DNA viruses that replicate in the cytoplasm of vertebrate and insect hosts and cause human and zoonotic diseases. In most cases the primary infection is moderated by innate immune defenses. Vertebrates, including fish, amphibians, reptiles, birds, and mammals, all produce type I interferon homologs. In humans, interferon stimulates the synthesis of more than 300 proteins thought to have roles in host defense. Conversely, viruses have evolved means to thwart the host defenses. We are attempting to deconstruct the established virus-host relationship in order to better understand the molecular mechanisms involved. In the present study, we identified a vaccinia virus gene that prevents interferon-mediated inhibition of very early stages of viral replication and is conserved in orthopoxviruses. The viral protein was shown to interact with host proteins involved in proteolysis, suggesting that vaccinia virus may subvert the cellular apparatus for its own defense. Copyright © 2018 American Society for Microbiology.

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

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

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

Genetic characteristics and pathogenic mechanisms of periodontal pathogens.

PubMed

Amano, A; Chen, C; Honma, K; Li, C; Settem, R P; Sharma, A

2014-05-01

Periodontal disease is caused by a group of bacteria that utilize a variety of strategies and molecular mechanisms to evade or overcome host defenses. Recent research has uncovered new evidence illuminating interesting aspects of the virulence of these bacteria and their genomic variability. This paper summarizes some of the strategies utilized by the major species - Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Treponema denticola, and Porphyromonas gingivalis - implicated in the pathogenesis of periodontal disease. Whole-genome sequencing of 14 diverse A. actinomycetemcomitans strains has revealed variations in their genetic content (ranging between 0.4% and 19.5%) and organization. Strikingly, isolates from human periodontal sites showed no genomic changes during persistent colonization. T. forsythia manipulates the cytokine responses of macrophages and monocytes through its surface glycosylation. Studies have revealed that bacterial surface-expressed O-linked glycans modulate T-cell responses during periodontal inflammation. Periodontal pathogens belonging to the "red complex" consortium express neuraminidases, which enables them to scavenge sialic acid from host glycoconjugates. Analysis of recent data has demonstrated that the cleaved sialic acid acts as an important nutrient for bacterial growth and a molecule for the decoration of bacteria surfaces to help evade the host immune attack. In addition, bacterial entry into host cells is also an important prerequisite for the lifestyle of periodontal pathogens such as P. gingivalis. Studies have shown that, after its entry into the cell, this bacterium uses multiple sorting pathways destined for autophagy, lysosomes, or recycling pathways. In addition, P. gingivalis releases outer membrane vesicles which enter cells via endocytosis and cause cellular functional impairment.

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

Bodily ownership modulation in defensive responses: physiological evidence in brain-damaged patients with pathological embodiment of other's body parts.

PubMed

Fossataro, C; Gindri, P; Mezzanato, T; Pia, L; Garbarini, F

2016-06-13

Do conscious beliefs about the body affect defensive mechanisms within the body? To answer this question we took advantage from a monothematic delusion of bodily ownership, in which brain-damaged patients misidentify alien limbs as their own. We investigated whether the delusional belief that an alien hand is their own hand modulates a subcortical defensive response, such as the hand-blink reflex. The blink, dramatically increases when the threated hand is inside the defensive peripersonal-space of the face. In our between-subjects design, including patients and controls, the threat was brought near the face either by the own hand or by another person's hand. Our results show an ownership-dependent modulation of the defensive response. In controls, as well as in the patients' intact-side, the response enhancement is significantly greater when the threat was brought near the face by the own than by the alien hand. Crucially, in the patients' affected-side (where the pathological embodiment occurs), the alien (embodied) hand elicited a response enhancement comparable to that found when the threat is brought near the face by the real hand. These findings suggest the existence of a mutual interaction between our conscious beliefs about the body and the physiological mechanisms within the body.

Nitric Oxide-Mediated Maintenance of Redox Homeostasis Contributes to NPR1-Dependent Plant Innate Immunity Triggered by Lipopolysaccharides1[C][W

PubMed Central

Sun, Aizhen; Nie, Shengjun; Xing, Da

2012-01-01

The perception of lipopolysaccharides (LPS) by plant cells can lead to nitric oxide (NO) production and defense gene induction. However, the signaling cascades underlying these cellular responses have not yet been resolved. This work investigated the biosynthetic origin of NO and the role of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) to gain insight into the mechanism involved in LPS-induced resistance of Arabidopsis (Arabidopsis thaliana). Analysis of inhibitors and mutants showed that LPS-induced NO synthesis was mainly mediated by an arginine-utilizing source of NO generation. Furthermore, LPS-induced NO caused transcript accumulation of alternative oxidase genes and increased antioxidant enzyme activity, which enhanced antioxidant capacity and modulated redox state. We also analyzed the subcellular localization of NPR1 to identify the mechanism for protein-modulated plant innate immunity triggered by LPS. LPS-activated defense responses, including callose deposition and defense-related gene expression, were found to be regulated through an NPR1-dependent pathway. In summary, a significant NO synthesis induced by LPS contributes to the LPS-induced defense responses by up-regulation of defense genes and modulation of cellular redox state. Moreover, NPR1 plays an important role in LPS-triggered plant innate immunity. PMID:22926319

Production of phytoalexins in peanut (Arachis hypogaea) seed elicited by selected microorganisms

USDA-ARS?s Scientific Manuscript database

Plants accumulate defensive phytoalexins in response to the presence of pathogens, which in turn produce phytoalexin-detoxification enzymes for successfully invading the plant host. The detoxification of a number of phytoalexins by phytopathogenic fungi has been elucidated for various host plant fam...

Type III Effector Diversification via Both Pathoadaptation and Horizontal Transfer in Response to a Coevolutionary Arms Race

PubMed Central

Ma, Wenbo; Dong, Frederick F. T; Stavrinides, John; Guttman, David S

2006-01-01

The concept of the coevolutionary arms race holds a central position in our understanding of pathogen–host interactions. Here we identify the molecular mechanisms and follow the stepwise progression of an arms race in a natural system. We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host. We surveyed 96 isolates of P. syringae and identified three homologs (HopZ1, HopZ2, and HopZ3) distributed among ∼45% of the strains. All alleles were sequenced and their expression was confirmed. Evolutionary analyses determined that the diverse HopZ1 homologs are ancestral to P. syringae, and have diverged via pathoadaptive mutational changes into three functional and two degenerate forms, while HopZ2 and HopZ3 have been brought into P. syringae via horizontal transfer from other ecologically similar bacteria. A PAML selection analysis revealed that the C terminus of HopZ1 is under strong positive selection. Despite the extensive genetic variation observed in this family, all three homologs have cysteine–protease activity, although their substrate specificity may vary. The introduction of the ancestral hopZ1 allele into strains harboring alternate alleles results in a resistance protein-mediated defense response in their respective hosts, which is not observed with the endogenous allele. These data indicate that the P. syringae HopZ family has undergone allelic diversification via both pathoadaptive mutational changes and horizontal transfer in response to selection imposed by the host defense system. This genetic diversity permits the pathogen to avoid host defenses while still maintaining a virulence-associated protease, thereby allowing it to thrive on its current host, while simultaneously impacting its host range. PMID:17194219

Role of transposon-derived small RNAs in the interplay between genomes and parasitic DNA in rice.

PubMed

Nosaka, Misuzu; Itoh, Jun-Ichi; Nagato, Yasuo; Ono, Akemi; Ishiwata, Aiko; Sato, Yutaka

2012-09-01

RNA silencing is a defense system against "genomic parasites" such as transposable elements (TE), which are potentially harmful to host genomes. In plants, transcripts from TEs induce production of double-stranded RNAs (dsRNAs) and are processed into small RNAs (small interfering RNAs, siRNAs) that suppress TEs by RNA-directed DNA methylation. Thus, the majority of TEs are epigenetically silenced. On the other hand, most of the eukaryotic genome is composed of TEs and their remnants, suggesting that TEs have evolved countermeasures against host-mediated silencing. Under some circumstances, TEs can become active and increase in copy number. Knowledge is accumulating on the mechanisms of TE silencing by the host; however, the mechanisms by which TEs counteract silencing are poorly understood. Here, we show that a class of TEs in rice produces a microRNA (miRNA) to suppress host silencing. Members of the microRNA820 (miR820) gene family are located within CACTA DNA transposons in rice and target a de novo DNA methyltransferase gene, OsDRM2, one of the components of epigenetic silencing. We confirmed that miR820 negatively regulates the expression of OsDRM2. In addition, we found that expression levels of various TEs are increased quite sensitively in response to decreased OsDRM2 expression and DNA methylation at TE loci. Furthermore, we found that the nucleotide sequence of miR820 and its recognition site within the target gene in some Oryza species have co-evolved to maintain their base-pairing ability. The co-evolution of these sequences provides evidence for the functionality of this regulation. Our results demonstrate how parasitic elements in the genome escape the host's defense machinery. Furthermore, our analysis of the regulation of OsDRM2 by miR820 sheds light on the action of transposon-derived small RNAs, not only as a defense mechanism for host genomes but also as a regulator of interactions between hosts and their parasitic elements.

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.

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

PubMed

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

2015-01-01

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