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Sample records for suppresses host defenses

  1. Conserved RXLR Effector Genes of Phytophthora infestans Expressed at the Early Stage of Potato Infection Are Suppressive to Host Defense

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    Junliang Yin

    2017-12-01

    Full Text Available Late blight has been the most devastating potato disease worldwide. The causal agent, Phytophthora infestans, is notorious for its capability to rapidly overcome host resistance. Changes in the expression pattern and the encoded protein sequences of effector genes in the pathogen are responsible for the loss of host resistance. Among numerous effector genes, the class of RXLR effector genes is well-known in mediating host genotype-specific resistance. We therefore performed deep sequencing of five genetically diverse P. infestans strains using in planta materials infected with zoospores (12 h post inoculation and focused on the identification of RXLR effector genes that are conserved in coding sequences, are highly expressed in early stages of plant infection, and have defense suppression activities. In all, 245 RXLR effector genes were expressed in five transcriptomes, with 108 being co-expressed in all five strains, 47 of them comparatively highly expressed. Taking sequence polymorphism into consideration, 18 candidate core RXLR effectors that were conserved in sequence and with higher in planta expression levels were selected for further study. Agrobacterium tumefaciens-mediated transient expression of the selected effector genes in Nicotiana benthamiana and potato demonstrated their potential virulence function, as shown by suppression of PAMP-triggered immunity (PTI or/and effector-triggered immunity (ETI. The identified collection of core RXLR effectors will be useful in the search for potential durable late blight resistance genes. Analysis of 10 known Avr RXLR genes revealed that the resistance genes R2, Rpi-blb2, Rpi-vnt1, Rpi-Smira1, and Rpi-Smira2 may be effective in potato cultivars. Analysis of 8 SFI (Suppressor of early Flg22-induced Immune response RXLR effector genes showed that SFI2, SFI3, and SFI4 were highly expressed in all examined strains, suggesting their potentially important function in early stages of pathogen infection.

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

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    Shawkat Ali

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

  3. The Inflammasome in Host Defense

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    Gang Chen

    2009-12-01

    Full Text Available Nod-like receptors have emerged as an important family of sensors in host defense. These receptors are expressed in macrophages, dendritic cells and monocytes and play an important role in microbial immunity. Some Nod-like receptors form the inflammasome, a protein complex that activates caspase-1 in response to several stimuli. Caspase-1 activation leads to processing and secretion of pro-inflammatory cytokines such as interleukin (IL-1β and IL-18. Here, we discuss recent advances in the inflammasome field with an emphasis on host defense. We also compare differential requirements for inflammasome activation in dendritic cells, macrophages and monocytes.

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

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

    2016-07-26

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

  5. Evasion of host immune defenses by human papillomavirus.

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    Westrich, Joseph A; Warren, Cody J; Pyeon, Dohun

    2017-03-02

    A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response

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    Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin

    2010-01-01

    Background/Aims Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1 levels could be used to determine the outcome after H. pylori infection. Methods Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression, whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation. PMID:20479912

  7. Suppressed Gastric Mucosal TGF-beta1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response.

    Science.gov (United States)

    Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin; Hahm, Ki-Baik

    2010-03-01

    Loss of transforming growth factor beta1 (TGF-beta1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-beta1 levels could be used to determine the outcome after H. pylori infection. Northern blot for the TGF-beta1 transcript, staining of TGF-beta1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-beta1 levels were performed at different times after H. pylori infection. The TGF-beta1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-beta1 levels. SNU-16 cells showing intact TGF-beta signaling exhibited a marked decrease in TGF-beta1 expression, whereas SNU-638 cells defective in TGF-beta signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-beta1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-beta1 is a host defense mechanism to avoid attachment of H. pylori. H. pylori infection was associated with depressed gastric mucosal TGF-beta1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.

  8. Host Defense Against Opportunist Microorganisms Following Trauma

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    1989-06-30

    Include Security Clasification ) (U) Host Defense Against Opportunist Microorganisms Following Trauma 12. PERSONAL AUTHOR(S) Bjornson, A. B., Bjornson...the course of bacterial and viral infec- tions. Infect. Immun. 30:824-831. 25. Zimmerli, W., B. Seligmann, and J. I. Gallin. 1986. Exudation primes

  9. Differences and Similarities of Soybean Defense-Related Genes Suppressed by Pathogenic and Symbiotic Bacteria

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    Bacterial effector proteins secreted through type III secretion systems (T3SS) play a crucial role in establishing plant and human diseases. Type III effectors have been shown to trigger defense responses when recognized by resistant plants, and to suppress defense responses in susceptible host plan...

  10. Interleukin-6 mediates host defense responses induced by abdominal surgery

    NARCIS (Netherlands)

    Wortel, C. H.; van Deventer, S. J.; Aarden, L. A.; Lygidakis, N. J.; Büller, H. R.; Hoek, F. J.; Horikx, J.; ten Cate, J. W.

    1993-01-01

    Cytokines have been implicated as pivotal mediators of the host defense reaction. In patients undergoing surgery we investigated the relationship between such mediators and postoperative host defense responses. Tumor necrosis factor (TNF) was determined with an immunoradiometric assay, interleukin

  11. Overcompensation of herbivore reproduction through hyper-suppression of plant defenses in response to competition.

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    Schimmel, Bernardus C J; Ataide, Livia M S; Chafi, Rachid; Villarroel, Carlos A; Alba, Juan M; Schuurink, Robert C; Kant, Merijn R

    2017-06-01

    Spider mites are destructive arthropod pests on many crops. The generalist herbivorous mite Tetranychus urticae induces defenses in tomato (Solanum lycopersicum) and this constrains its fitness. By contrast, the Solanaceae-specialist Tetranychus evansi maintains a high reproductive performance by suppressing tomato defenses. Tetranychus evansi outcompetes T. urticae when infesting the same plant, but it is unknown whether this is facilitated by the defenses of the plant. We assessed the extent to which a secondary infestation by a competitor affects local plant defense responses (phytohormones and defense genes), mite gene expression and mite performance. We observed that T. evansi switches to hyper-suppression of defenses after its tomato host is also invaded by its natural competitor T. urticae. Jasmonate (JA) and salicylate (SA) defenses were suppressed more strongly, albeit only locally at the feeding site of T. evansi, upon introduction of T. urticae to the infested leaflet. The hyper-suppression of defenses coincided with increased expression of T. evansi genes coding for salivary defense-suppressing effector proteins and was paralleled by an increased reproductive performance. Together, these observations suggest that T. evansi overcompensates its reproduction through hyper-suppression of plant defenses in response to nearby competitors. We hypothesize that the competitor-induced overcompensation promotes competitive population growth of T. evansi on tomato. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  12. Subversion and utilization of host innate defense by Leishmania amazonensis

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    Lynn eSoong

    2012-03-01

    Full Text Available Infection with Leishmania amazonensis and other members of the L. mexicana complex can lead to diverse clinical manifestations, some of which are relatively difficult to control, even with standard chemotherapy. Diffuse cutaneous leishmaniasis is a rare but severe form, and its clinical hallmark is excessive parasitic growth in infected cells accompanied by profound impairments in host immune responses to the parasites. Since these parasites also cause non-healing cutaneous leishmaniasis in most inbred strains of mice, these animals are valuable models for dissecting the mechanisms of persistent infection and disease pathogenesis. In comparison to other Leishmania species, L. amazonensis infections are most remarkable for their ability to repress the activation and effector functions of macrophages, dendritic cells and CD4+ T cells, implying discrete mechanisms at work. In addition to this multilateral suppression of host innate and adaptive immunity, the activation of types I and II interferon-mediated responses and autophagic/lipid metabolic pathways actually promotes rather than restrains L. amazonensis infection. These seemingly contradictory findings reflect the remarkable adaptation of the parasites to the ancient defense machinery of the host, as well as the complex parasite-host interactions at different stages of infection, which collectively contribute to non-healing leishmaniasis in the New World. This review article highlights new evidence that reveals the strategies utilized by L. amazonensis parasites to subvert or modulate host innate defense machinery in neutrophils and macrophages, as well as the regulatory roles of host innate responses in promoting parasite survival and replication within the huge parasitophorous vacuoles. A better understanding of unique features in host responses to these parasites at early and late stages of infection is important for the rational design of control strategies for non-healing leishmaniasis.

  13. Subversion and Utilization of Host Innate Defense by Leishmania amazonensis.

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    Soong, Lynn

    2012-01-01

    Infection with Leishmania amazonensis and other members of the Leishmania mexicana complex can lead to diverse clinical manifestations, some of which are relatively difficult to control, even with standard chemotherapy. Diffuse cutaneous leishmaniasis (CL) is a rare but severe form, and its clinical hallmark is excessive parasitic growth in infected cells accompanied by profound impairments in host immune responses to the parasites. Since these parasites also cause non-healing CL in most inbred strains of mice, these animals are valuable models for dissecting the mechanisms of persistent infection and disease pathogenesis. In comparison to other Leishmania species, L. amazonensis infections are most remarkable for their ability to repress the activation and effector functions of macrophages, dendritic cells, and CD4(+) T cells, implying discrete mechanisms at work. In addition to this multilateral suppression of host innate and adaptive immunity, the activation of types I and II interferon-mediated responses and autophagic/lipid metabolic pathways actually promotes rather than restrains L. amazonensis infection. These seemingly contradictory findings reflect the remarkable adaptation of the parasites to the ancient defense machinery of the host, as well as the complex parasite-host interactions at different stages of infection, which collectively contribute to non-healing leishmaniasis in the New World. This review article highlights new evidence that reveals the strategies utilized by L. amazonensis parasites to subvert or modulate host innate defense machinery in neutrophils and macrophages, as well as the regulatory roles of host innate responses in promoting parasite survival and replication within the huge parasitophorous vacuoles. A better understanding of unique features in host responses to these parasites at early and late stages of infection is important for the rational design of control strategies for non-healing leishmaniasis.

  14. Necroptosis: The Trojan horse in cell autonomous antiviral host defense.

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    Mocarski, Edward S; Guo, Hongyan; Kaiser, William J

    2015-05-01

    Herpesviruses suppress cell death to assure sustained infection in their natural hosts. Murine cytomegalovirus (MCMV) encodes suppressors of apoptosis as well as M45-encoded viral inhibitor of RIP activation (vIRA) to block RIP homotypic interaction motif (RHIM)-signaling and recruitment of RIP3 (also called RIPK3), to prevent necroptosis. MCMV and human cytomegalovirus encode a viral inhibitor of caspase (Casp)8 activation to block apoptosis, an activity that unleashes necroptosis. Herpes simplex virus (HSV)1 and HSV2 incorporate both RHIM and Casp8 suppression strategies within UL39-encoded ICP6 and ICP10, respectively, which are herpesvirus-conserved homologs of MCMV M45. Both HSV proteins sensitize human cells to necroptosis by blocking Casp8 activity while preventing RHIM-dependent RIP3 activation and death. In mouse cells, HSV1 ICP6 interacts with RIP3 and, surprisingly, drives necroptosis. Thus, herpesviruses have illuminated the contribution of necoptosis to host defense in the natural host as well as its potential to restrict cross-species infections in nonnatural hosts. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Molecular mechanisms of epithelial host defense in the airways

    NARCIS (Netherlands)

    Vos, Joost Bastiaan

    2007-01-01

    Airway epithelial cells are indispensable for the host defense system in the lungs. Various strategies by which epithelial cells protect the lungs against inhaled pathogens have been described. In spite of that, the molecular mechanisms by which epithelial cells initiate and control the host defense

  16. Fungal Recognition and Host Defense Mechanisms.

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    Dambuza, I M; Levitz, S M; Netea, M G; Brown, G D

    2017-07-01

    Fungi have emerged as premier opportunistic microbes of the 21st century, having a considerable impact on human morbidity and mortality. The huge increase in incidence of these diseases is largely due to the HIV pandemic and use of immunosuppressive therapies, underscoring the importance of the immune system in defense against fungi. This article will address how the mammalian immune system recognizes and mounts a defense against medically relevant fungal species.

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

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    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.…

  18. Carp erythrodermatitis : host defense-pathogen interaction

    NARCIS (Netherlands)

    Pourreau, C.N.

    1990-01-01

    The outcome of a bacterial infection depends on the interaction between pathogen and host. The ability of the microbe to survive in the host depends on its invasive potential (i.e. spreading and multiplication), and its ability to obtain essential nutrients and to resist the

  19. Soluble Host Defense Lectins in Innate Immunity to Influenza Virus

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    Ng, Wy Ching; Tate, Michelle D.; Brooks, Andrew G.; Reading, Patrick C.

    2012-01-01

    Host defenses against viral infections depend on a complex interplay of innate (nonspecific) and adaptive (specific) components. In the early stages of infection, innate mechanisms represent the main line of host defense, acting to limit the spread of virus in host tissues prior to the induction of the adaptive immune response. Serum and lung fluids contain a range of lectins capable of recognizing and destroying influenza A viruses (IAV). Herein, we review the mechanisms by which soluble endogenous lectins mediate anti-IAV activity, including their role in modulating IAV-induced inflammation and disease and their potential as prophylactic and/or therapeutic treatments during severe IAV-induced disease. PMID:22665991

  20. Innate host defense against intracellular pathogens

    NARCIS (Netherlands)

    Vaart, Michiel van der

    2013-01-01

    This thesis focuses on the recognition of pathogenic bacteria and the defense mechanisms that are activated during the innate immune response to infection. Detection of pathogens, such as bacteria, viruses, and parasites, depends on receptors that bind to evolutionary conserved structures on their

  1. Not to be suppressed? Rethinking the host response at a root-parasite interface.

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    Goto, Derek B; Miyazawa, Hikota; Mar, Jessica C; Sato, Masanao

    2013-12-01

    Root-knot nematodes are highly efficient plant parasites that establish permanent feeding sites within host roots. The initiation of this feeding site is critical for parasitic success and requires an interaction with multiple signaling pathways involved in plant development and environmental response. Resistance against root-knot nematodes is relatively rare amongst their broad host range and they remain a major threat to agriculture. The development of effective and sustainable control strategies depends on understanding how host signaling pathways are manipulated during invasion of susceptible hosts. It is generally understood that root-knot nematodes either suppress host defense signaling during infestation or are able to avoid detection altogether, explaining their profound success as parasites. However, when compared to the depth of knowledge from other well-studied pathogen interactions, the published data on host responses to root-knot nematode infestation do not yet provide convincing support for this hypothesis and alternative explanations also exist. It is equally possible that defense-like signaling responses are actually induced and required during the early stages of root-knot nematode infestation. We describe how defense-signaling is highly context-dependent and that caution is necessary when interpreting transcriptional responses in the absence of appropriate control data or stringent validation of gene annotation. Further hypothesis-driven studies on host defense-like responses are required to account for these limitations and advance our understanding of root-knot nematode parasitism of plants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. CXCR1 regulates pulmonary anti-Pseudomonas host defense

    Science.gov (United States)

    Carevic, M.; Öz, H.; Fuchs, K.; Laval, J.; Schroth, C.; Frey, N.; Hector, A.; Bilich, T.; Haug, M.; Schmidt, A.; Autenrieth, S. E.; Bucher, K.; Beer-Hammer, S.; Gaggar, A.; Kneilling, M.; Benarafa, C.; Gao, J.; Murphy, P.; Schwarz, S.; Moepps, B.; Hartl, D.

    2016-01-01

    Pseudomonas aeruginosa is a key opportunistic pathogen causing disease in cystic fibrosis (CF) and other lung diseases such as chronic obstructive pulmonary disease (COPD). However, the pulmonary host defense mechanisms regulating anti-Pseudomonas aeruginosa immunity remain incompletely understood. Here we demonstrate, by studying an airway Pseudomonas aeruginosa infection model, in vivo bioluminescence imaging, neutrophil effector responses and human airway samples, that the chemokine receptor CXCR1 regulates pulmonary host defense against Pseudomonas aeruginosa. Mechanistically, CXCR1 regulated anti-Pseudomonas neutrophil responses through modulation of reactive oxygen species and interference with toll-like receptor 5 expression. These studies define CXCR1 as a novel non-canonical chemokine receptor that regulates pulmonary anti-Pseudomonas host defense with broad implications for CF, COPD and other infectious lung diseases. PMID:26950764

  3. Characterization of a proteolytically stable multifunctional host defense peptidomimetic

    DEFF Research Database (Denmark)

    Jahnsen, Rasmus D; Haney, Evan F; Franzyk, Henrik

    2013-01-01

    The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory concentra......The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory...

  4. Expression of host defense scavenger receptors in spondylarthropathy

    NARCIS (Netherlands)

    Seta, N.; Granfors, K.; Sahly, H.; Kuipers, J. G.; Song, Y. W.; Baeten, D.; Veys, E. M.; Maksymowych, W.; Märker-Hermann, E.; Gu, J.; Huang, F.; Kirveskari, J.; Yu, D. T.

    2001-01-01

    OBJECTIVE: Reactive arthritis (ReA) is postulated to be caused by a defective host defense against gram-negative bacteria. HLA-B27 could play a role in this process, but does not account for the many HLA-B27 negative patients. The objective of this study was to test the expression of 3 macrophage

  5. Gut microbiota and host defense in critical illness

    NARCIS (Netherlands)

    Jacobs, Max C.; Haak, Bastiaan W.; Hugenholtz, Floor; Wiersinga, W. Joost

    2017-01-01

    Purpose of reviewThe review aims to discuss emerging evidence in the field of microbiome-dependent roles in host defense during critical illness with a focus on lung, kidney, and brain inflammation.Recent findingsThe gut microbiota of critical ill patients is characterized by lower diversity, lower

  6. Impact of Childhood Malnutrition on Host Defense and Infection.

    Science.gov (United States)

    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.

  7. Histones as mediators of host defense, inflammation and thrombosis

    NARCIS (Netherlands)

    Hoeksema, Marloes; Eijk, Martin van; Haagsman, Henk P; Hartshorn, Kevan L

    2016-01-01

    Histones are known for their ability to bind to and regulate expression of DNA. However, histones are also present in cytoplasm and extracellular fluids where they serve host defense functions and promote inflammatory responses. Histones are a major component of neutrophil extracellular traps that

  8. Host Defense Mechanisms against Bark Beetle Attack Differ between Ponderosa and Lodgepole Pines

    OpenAIRE

    Daniel R. West; Elisa J. Bernklau; Louis B. Bjostad; William R. Jacobi

    2016-01-01

    Conifer defenses against bark beetle attack include, but are not limited to, quantitative and qualitative defenses produced prior to attack. Our objective was to assess host defenses of lodgepole pine and ponderosa pine from ecotone stands. These stands provide a transition of host species for mountain pine beetle (Dendroctonus ponderosae; MPB). We asked two questions: (1) do the preformed quantitative host defenses (amount of resin) and (2) the preformed qualitative host defenses (monoterpen...

  9. Defense suppression benefits herbivores that have a monopoly on their feeding site but can backfire within natural communities.

    Science.gov (United States)

    Glas, Joris J; Alba, Juan M; Simoni, Sauro; Villarroel, Carlos A; Stoops, Marije; Schimmel, Bernardus Cj; Schuurink, Robert C; Sabelis, Maurice W; Kant, Merijn R

    2014-11-18

    can be a consequence, rather than the cause, of a primary suppression event and that its overall effect is determined by the presence of competing herbivores and the distinct palette of defenses these induce. Thus, whether or not host-defense manipulation improves an herbivore's fitness depends on interactions with other herbivores via induced-host defenses, implicating bidirectional causation of community structure of herbivores sharing a plant.

  10. Diverse mechanisms evolved by DNA viruses to inhibit early host defenses

    Science.gov (United States)

    Sheng, Xinlei; Song, Bokai; Cristea, Ileana M.

    2016-01-01

    In mammalian cells, early defenses against infection by pathogens are mounted through a complex network of signaling pathways shepherded by immune-modulatory pattern-recognition receptors. As obligate parasites, the survival of viruses is dependent upon the evolutionary acquisition of mechanisms that tactfully dismantle and subvert the cellular intrinsic and innate immune responses. Here, we review the diverse mechanisms by which viruses that accommodate DNA genomes are able to circumvent activation of cellular immunity. We start by discussing viral manipulation of host defense protein levels by either transcriptional regulation or protein degradation. We next review viral strategies used to repurpose or inhibit these cellular immune factors by molecular hijacking or by regulating their post-translational modification status. Additionally, we explore the infection-induced temporal modulation of apoptosis to facilitate viral replication and spread. Lastly, the co-evolution of viruses with their hosts is highlighted by the acquisition of elegant mechanisms for suppressing host defenses via viral mimicry of host factors. In closing, we present a perspective on how characterizing these viral evasion tactics both broadens the understanding of virus-host interactions and reveals essential functions of the immune system at the molecular level. This knowledge is critical in understanding the sources of viral pathogenesis, as well as for the design of antiviral therapeutics and autoimmunity treatments. PMID:27650455

  11. Insights from human studies into the host defense against candidiasis.

    Science.gov (United States)

    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.

  12. NOD1-Mediated Mucosal Host Defense against Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Tomohiro Watanabe

    2010-01-01

    Full Text Available Infection of the stomach with Helicobacter pylori is an important risk factor for gastritis, peptic ulcer, and gastric carcinoma. Although it has been well established that persistent colonization by H. pylori is associated with adaptive Th1 responses, the innate immune responses leading to these Th1 responses are poorly defined. Recent studies have shown that the activation of nucleotide-binding oligomerization domain 1 (NOD1 in gastric epithelial cells plays an important role in innate immune responses against H. pylori. The detection of H. pylori-derived ligands by cytosolic NOD1 induces several host defense factors, including antimicrobial peptides, cytokines, and chemokines. In this paper, we review the molecular mechanisms by which NOD1 contributes to mucosal host defense against H. pylori infection of the stomach.

  13. Histones as mediators of host defense, inflammation and thrombosis

    OpenAIRE

    Hoeksema, Marloes; van Eijk, Martin; Haagsman, Henk P; Hartshorn, Kevan L

    2016-01-01

    Histones are known for their ability to bind to and regulate expression of DNA. However, histones are also present in cytoplasm and extracellular fluids where they serve host defense functions and promote inflammatory responses. Histones are a major component of neutrophil extracellular traps that contribute to bacterial killing but also to inflammatory injury. Histones can act as antimicrobial peptides and directly kill bacteria, fungi, parasites and viruses, in vitro and in a variety of ani...

  14. Necroptosis: The Trojan Horse in Cell Autonomous Antiviral Host Defense

    OpenAIRE

    Mocarski, Edward S.; Guo, Hongyan; Kaiser, William J.

    2015-01-01

    Herpesviruses suppress cell death to assure sustained infection in their natural hosts. Murine cytomegalovirus (MCMV) encodes suppressors of apoptosis as well as M45-encoded viral inhibitor of RIP activation (vIRA) to block RIP homotypic interaction motif (RHIM)-signaling and recruitment of RIP3 (also called RIPK3), to prevent necroptosis. MCMV and human cytomegalovirus encode a viral inhibitor of caspase (Casp)8 activation to blocks apoptosis, an activity that unleashes necroptosis. Herpes s...

  15. Salivary mucins in host defense and disease prevention

    Directory of Open Access Journals (Sweden)

    Erica Shapiro Frenkel

    2015-12-01

    Full Text Available Mucus forms a protective coating on wet epithelial surfaces throughout the body that houses the microbiota and plays a key role in host defense. Mucins, the primary structural components of mucus that creates its viscoelastic properties, are critical components of the gel layer that protect against invading pathogens. Altered mucin production has been implicated in diseases such as ulcerative colitis, asthma, and cystic fibrosis, which highlights the importance of mucins in maintaining homeostasis. Different types of mucins exist throughout the body in various locations such as the gastrointestinal tract, lungs, and female genital tract, but this review will focus on mucins in the oral cavity. Salivary mucin structure, localization within the oral cavity, and defense mechanisms will be discussed. These concepts will then be applied to present what is known about the protective function of mucins in oral diseases such as HIV/AIDS, oral candidiasis, and dental caries.

  16. Host Defense Peptides from Asian Frogs as Potential Clinical Therapies

    Science.gov (United States)

    Kumar, Vineeth T.V.; Holthausen, David; Jacob, Joshy; George, Sanil

    2015-01-01

    Host defense peptides (HDPs) are currently major focal points of medical research as infectious microbes are gaining resistance to existing drugs. They are effective against multi-drug resistant pathogens due to their unique primary target, biological membranes, and their peculiar mode of action. Even though HDPs from 60 Asian frog species belonging to 15 genera have been characterized, research into these peptides is at a very early stage. The purpose of this review is to showcase the status of peptide research in Asia. Here we provide a summary of HDPs from Asian frogs. PMID:27025618

  17. Histones as mediators of host defense, inflammation and thrombosis.

    Science.gov (United States)

    Hoeksema, Marloes; van Eijk, Martin; Haagsman, Henk P; Hartshorn, Kevan L

    2016-01-01

    Histones are known for their ability to bind to and regulate expression of DNA. However, histones are also present in cytoplasm and extracellular fluids where they serve host defense functions and promote inflammatory responses. Histones are a major component of neutrophil extracellular traps that contribute to bacterial killing but also to inflammatory injury. Histones can act as antimicrobial peptides and directly kill bacteria, fungi, parasites and viruses, in vitro and in a variety of animal hosts. In addition, histones can trigger inflammatory responses in some cases acting through Toll-like receptors or inflammasome pathways. Extracellular histones mediate organ injury (lung, liver), sepsis physiology, thrombocytopenia and thrombin generation and some proteins can bind histones and reduce these potentially harmful effects.

  18. Chronic pyelonephritis: Modulation of host defenses by cyclosporin A

    International Nuclear Information System (INIS)

    Findon, G.; Miller, T.E.

    1989-01-01

    Chronic experimental pyelonephritis is characterized by a stable level of infection, which persists for many months. Administration of cyclosporin A (CsA) reactivated previously healed renal lesions and caused a marked increase in bacterial numbers in the kidney. Studies were then carried out to compare the effects of CsA, and the nonselective cytodepletive agents irradiation and cyclophosphamide, on both host defenses and the bacteriologic status of chronically infected kidneys. Two different responses were observed. In animals treated with CsA, bacterial numbers increased markedly, although circulating neutrophil numbers were relatively unaffected. This observation was in contrast to the severe ablation of leukocyte numbers and competence needed to achieve an equivalent effect when irradiation and cyclophosphamide were used. One possible explanation for the adverse effect of CsA on the host-parasite balance in chronic pyelonephritis is that CsA affects mediators that control the inflammatory response or induces a qualitative change in a critical cellular defense compartment

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

    Science.gov (United States)

    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

  20. Guardian of the Human Genome: Host Defense Mechanisms against LINE-1 Retrotransposition.

    Science.gov (United States)

    Ariumi, Yasuo

    2016-01-01

    Long interspersed element type 1 (LINE-1, L1) is a mobile genetic element comprising about 17% of the human genome, encoding a newly identified ORF0 with unknown function, ORF1p with RNA-binding activity and ORF2p with endonuclease and reverse transcriptase activities required for L1 retrotransposition. L1 utilizes an endonuclease (EN) to insert L1 cDNA into target DNA, which induces DNA double-strand breaks (DSBs). The ataxia-telangiectasia mutated (ATM) is activated by DSBs and subsequently the ATM-signaling pathway plays a role in regulating L1 retrotransposition. In addition, the host DNA repair machinery such as non-homologous end-joining (NHEJ) repair pathway is also involved in L1 retrotransposition. On the other hand, L1 is an insertional mutagenic agent, which contributes to genetic change, genomic instability, and tumorigenesis. Indeed, high-throughput sequencing-based approaches identified numerous tumor-specific somatic L1 insertions in variety of cancers, such as colon cancer, breast cancer, and hepatocellular carcinoma (HCC). In fact, L1 retrotransposition seems to be a potential factor to reduce the tumor suppressive property in HCC. Furthermore, recent study demonstrated that a specific viral-human chimeric transcript, HBx-L1, contributes to hepatitis B virus (HBV)-associated HCC. In contrast, host cells have evolved several defense mechanisms protecting cells against retrotransposition including epigenetic regulation through DNA methylation and host defense factors, such as APOBEC3, MOV10, and SAMHD1, which restrict L1 mobility as a guardian of the human genome. In this review, I focus on somatic L1 insertions into the human genome in cancers and host defense mechanisms against deleterious L1 insertions.

  1. Host plant defense signaling in response to a coevolved herbivore combats introduced herbivore attack

    OpenAIRE

    Woodard, Anastasia M; Ervin, Gary N; Marsico, Travis D

    2012-01-01

    Defense-free space resulting from coevolutionarily naïve host plants recently has been implicated as a factor facilitating invasion success of some insect species. Host plants, however, may not be entirely defenseless against novel herbivore threats. Volatile chemical-mediated defense signaling, which allows plants to mount specific, rapid, and intense responses, may play a role in systems experiencing novel threats. Here we investigate defense responses of host plants to a native and exotic ...

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

    Science.gov (United States)

    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

  3. Coronavirus gene 7 counteracts host defenses and modulates virus virulence.

    Science.gov (United States)

    Cruz, Jazmina L G; Sola, Isabel; Becares, Martina; Alberca, Berta; Plana, Joan; Enjuanes, Luis; Zuñiga, Sonia

    2011-06-01

    Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of

  4. Coronavirus gene 7 counteracts host defenses and modulates virus virulence.

    Directory of Open Access Journals (Sweden)

    Jazmina L G Cruz

    2011-06-01

    Full Text Available Transmissible gastroenteritis virus (TGEV genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7. Both the mutant and the parental (rTGEV-wt viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c, a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the

  5. Insect herbivores selectively suppress the HPL branch of the oxylipin pathway in host plants.

    Science.gov (United States)

    Savchenko, Tatyana; Pearse, Ian S; Ignatia, Laura; Karban, Richard; Dehesh, Katayoon

    2013-02-01

    Insect herbivores have developed a myriad of strategies to manipulate the defense responses of their host plants. Here we provide evidence that chewing insects differentially alter the oxylipin profiles produced by the two main and competing branches of the plant defensive response pathway, the allene oxide synthase (AOS) and hydroperoxide lyase (HPL) branches, which are responsible for wound-inducible production of jasmonates (JAs), and green leafy volatiles (GLVs) respectively. Specifically, we used three Arabidopsis genotypes that were damaged by mechanical wounding or by insects of various feeding guilds (piercing aphids, generalist chewing caterpillars and specialist chewing caterpillars). We established that emission of GLVs is stimulated by wounding incurred mechanically or by aphids, but release of these volatiles is constitutively impaired by both generalist and specialist chewing insects. Simultaneously, however, these chewing herbivores stimulated JA production, demonstrating targeted insect suppression of the HPL branch of the oxylipin pathway. Use of lines engineered to express HPL constitutively, in conjunction with quantitative RT-PCR-based expression analyses, established a combination of transcriptional and post-transcriptional reprogramming of the HPL pathway genes as the mechanistic basis of insect-mediated suppression of the corresponding metabolites. Feeding studies suggested a potential evolutionary advantage of suppressing GLV production, as caterpillars preferably consumed leaf tissue from plants that had not been primed by these volatile cues. © 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.

  6. Designed Host Defense Peptides for the Treatment of Bacterial Keratitis.

    Science.gov (United States)

    Clemens, L Edward; Jaynes, Jesse; Lim, Edward; Kolar, Satya S; Reins, Rose Y; Baidouri, Hasna; Hanlon, Samuel; McDermott, Alison M; Woodburn, Kathryn W

    2017-12-01

    To limit corneal damage and potential loss of vision, bacterial keratitis must be treated aggressively. Innovation in antimicrobials is required due to the need for empirical treatment and the rapid emergence of bacterial resistance. Designed host defense peptides (dHDPs) are synthetic analogues of naturally occurring HDPs, which provide defense against invading pathogens. This study investigates the use of novel dHDPs for the treatment of bacterial keratitis. The minimum inhibitory concentrations (MICs) were determined for dHDPs on both Gram-positive and -negative bacteria. The minimum biofilm eradication concentrations (MBEC) and in vitro time-kill assays were determined. The most active dHDP, RP444, was evaluated for propensity to induce drug resistance and therapeutic benefit in a murine Pseudomonas aeruginosa keratitis model. Designed HDPs were bactericidal with MICs ranging from 2 to >64 μg/mL and MBEC ranging from 6 to 750 μg/mL. In time-kill assays, dHDPs were able to rapidly reduce bacterial counts upon contact with as little as 2 μg/mL. RP444 did not induce resistance after repeated exposure of P. aeruginosa to subinhibitory concentrations. RP444 demonstrated significant efficacy in a murine model of bacterial keratitis as evidenced by a significant dose-dependent decrease in ocular clinical scores, a significantly reduced bacterial load, and substantially decreased inflammatory cell infiltrates. Innovative dHDPs demonstrated potent antimicrobial activity, possess a limited potential for development of resistance, and reduced the severity of murine P. aeruginosa keratitis. These studies demonstrate that a novel dHDP may have potential to treat patients with sight-threatening bacterial keratitis.

  7. Symbiotic Bacteria Enable Olive Fly Larvae to Overcome Host Defenses

    International Nuclear Information System (INIS)

    Ben-Yosef, Michael; Yuval, Boaz; Pasternak, Zohar; Jurkevitch, Edouard

    2016-01-01

    Ripe fruit offer readily available nutrients for many animals, including fruit fly larvae (Diptera: Tephritidae) and their associated rot-inducing bacteria. Yet, during most of their ontogeny, fruit remain chemically defended and effectively suppress herbivores and pathogens by high levels of secondary metabolites. Olive flies (Bactrocera oleae) are uniquely able to develop in unripe olives. Unlike other frugivorous tephritids, the larvae maintain bacteria confined within their midgut caeca. We examined the interaction between larvae, their associated bacteria, and fruit chemical defence, hypothesizing that bacterial contribution to larval development is contingent on the phenology of fruit defensive chemistry. We demonstrate that larvae require their natural complement of bacteria (Candidatus Erwinia dacicola: Enterobacteriaceae) in order to develop in unripe olives. Conversely, when feeding on ripe fruit, larval development proceeds independently of these bacteria. Our experiments suggest that bacteria counteract the inhibitory effect of oleuropein—the principal phenolic glycoside in unripe olives. In light of these results, we suggest that the unique symbiosis in olive flies, compared with other frugivorous tephritids, is understood by considering the relationship between the fly, bacteria and fruit chemistry. When applied in an evolutionary context, this approach may also point out the forces which shaped symbioses across the Tephritidae. (author)

  8. The Ustilago maydis effector Pep1 suppresses plant immunity by inhibition of host peroxidase activity.

    Directory of Open Access Journals (Sweden)

    Christoph Hemetsberger

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

  9. Interferon induced IFIT family genes in host antiviral defense.

    Science.gov (United States)

    Zhou, Xiang; Michal, Jennifer J; Zhang, Lifan; Ding, Bo; Lunney, Joan K; Liu, Bang; Jiang, Zhihua

    2013-01-01

    Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals.

  10. DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism

  11. Defense suppression benefits herbivores that have a monopoly on their feeding site but can backfire within natural communities

    NARCIS (Netherlands)

    Glas, J.J.; Alba, J.M.; Simoni, S.; Villarroel, C.A.; Stoops, M.; Schimmel, B.C.J.; Schuurink, R.C.; Sabelis, M.W.; Kant, M.R.

    2014-01-01

    Background: Plants have inducible defenses to combat attacking organisms. Hence, some herbivores have adapted to suppress these defenses. Suppression of plant defenses has been shown to benefit herbivores by boosting their growth and reproductive performance. Results: We observed in field-grown

  12. Molecular sabotage of host plant defenses by spider mites

    NARCIS (Netherlands)

    Villarroel Figueroa, C.A.

    2016-01-01

    Plants constitute an ample source of nutrients for a diversity of organisms that include viruses, microbes, nematodes, insects, and mites. To protect their resources, plants possess a robust immune system that establishes structural and biochemical defenses to fight invaders. Some of these defenses

  13. The Listeria monocytogenes ChiA chitinase enhances virulence through suppression of host innate immunity.

    Science.gov (United States)

    Chaudhuri, Swarnava; Gantner, Benjamin N; Ye, Richard D; Cianciotto, Nicholas P; Freitag, Nancy E

    2013-03-19

    Environmental pathogens survive and replicate within the outside environment while maintaining the capacity to infect mammalian hosts. For some microorganisms, mammalian infection may be a relatively rare event. Understanding how environmental pathogens retain their ability to cause disease may provide insight into environmental reservoirs of disease and emerging infections. Listeria monocytogenes survives as a saprophyte in soil but is capable of causing serious invasive disease in susceptible individuals. The bacterium secretes virulence factors that promote cell invasion, bacterial replication, and cell-to-cell spread. Recently, an L. monocytogenes chitinase (ChiA) was shown to enhance bacterial infection in mice. Given that mammals do not synthesize chitin, the function of ChiA within infected animals was not clear. Here we have demonstrated that ChiA enhances L. monocytogenes survival in vivo through the suppression of host innate immunity. L. monocytogenes ΔchiA mutants were fully capable of establishing bacterial replication within target organs during the first 48 h of infection. By 72 to 96 h postinfection, however, numbers of ΔchiA bacteria diminished, indicative of an effective immune response to contain infection. The ΔchiA-associated virulence defect could be complemented in trans by wild-type L. monocytogenes, suggesting that secreted ChiA altered a target that resulted in a more permissive host environment for bacterial replication. ChiA secretion resulted in a dramatic decrease in inducible nitric oxide synthase (iNOS) expression, and ΔchiA mutant virulence was restored in NOS2(-/-) mice lacking iNOS. This work is the first to demonstrate modulation of a specific host innate immune response by a bacterial chitinase. Bacterial chitinases have traditionally been viewed as enzymes that either hydrolyze chitin as a food source or serve as a defense mechanism against organisms containing structural chitin (such as fungi). Recent evidence indicates

  14. Innate host defense of the lung: effects of lung-lining fluid pH.

    Science.gov (United States)

    Ng, Amelia W; Bidani, Akhil; Heming, Thomas A

    2004-01-01

    Lung-lining fluid (LLF) is a primary constituent of the pulmonary host defense system. It is distributed continuously throughout the respiratory tract but is heterogeneous regarding its chemistry and physiology between the conducting airways and alveoli. The conducting airways are lined with airway surface liquid (ASL), a mucus gel-aqueous sol complex that interacts functionally with epithelial cilia as the mucociliary escalator. The alveoli are lined with alveolar subphase fluid (AVSF) and pulmonary surfactant. AVSF sterility is maintained in part by the phagocytic activity of resident alveolar macrophages. Normal ASL and AVSF are both more acidic than blood plasma. However, the details of acid-base regulation differ between the two media. Appreciable transepithelial acid-base flux is possible across the airway epithelium, whereas the alveolar epithelium is relatively impermeable to transepithelial acid-base flux. Moreover, one must consider the influence of resident macrophages on AVSF pH. Resident macrophages occupy a sizable fraction of AVSF by volume and are a substantial source of metabolic H+. The buffering capacities of ASL and AVSF probably are largely due to secreted peptides (e.g., ASL mucins and AVSF surfactant proteins). Acid-base exchange between the extracellular hydrophase and intracellular buffering systems of resident macrophages represents an additional buffer pool for AVSF. The pH of ASL and AVSF can be depressed by disease or inflammation. Low pH is predicted to suppress microbe clearance from the airways and alveoli, increase pathogen survival in both regions, and alter mediator release by resident macrophages and recruited leukocytes thereby increasing the propensity for bystander cell injury. Overall, ASL/AVSF pH is expected to be a major determinant of lung host defense responses.

  15. Interplay between Candida albicans and the Mammalian Innate Host Defense

    Science.gov (United States)

    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

  16. Host Niches and Defensive Extended Phenotypes Structure Parasitoid Wasp Communities

    OpenAIRE

    Bailey, Richard; Schonrogge, Karsten; Cook, James M.; Melika, George; Csoka, Gyorgy; Thuroczy, Csaba; Stone, Graham N.

    2009-01-01

    Oak galls are spectacular extended phenotypes of gallwasp genes in host oak tissues and have evolved complex morphologies that serve, in part, to exclude parasitoid natural enemies. Parasitoids and their insect herbivore hosts have coevolved to produce diverse communities comprising about a third of all animal species. The factors structuring these communities, however, remain poorly understood. An emerging theme in community ecology is the need to consider the effects of host traits, shaped ...

  17. Host Defense Mechanisms against Bark Beetle Attack Differ between Ponderosa and Lodgepole Pines

    Directory of Open Access Journals (Sweden)

    Daniel R. West

    2016-10-01

    Full Text Available Conifer defenses against bark beetle attack include, but are not limited to, quantitative and qualitative defenses produced prior to attack. Our objective was to assess host defenses of lodgepole pine and ponderosa pine from ecotone stands. These stands provide a transition of host species for mountain pine beetle (Dendroctonus ponderosae; MPB. We asked two questions: (1 do the preformed quantitative host defenses (amount of resin and (2 the preformed qualitative host defenses (monoterpene constituents differ between lodgepole and ponderosa pines. We collected oleoresins at three locations in the Southern Rocky Mountains from 56 pairs of the pine species of similar size and growing conditions. The amount of preformed-ponderosa pine oleoresins exuded in 24 h (mg was almost four times that of lodgepole pine. Total qualitative preformed monoterpenes did not differ between the two hosts, though we found differences in all but three monoterpenes. No differences were detected in α-pinene, γ-terpinene, and bornyl acetate. We found greater concentrations of limonene, β-phellandrene, and cymene in lodgepole pines, whereas β-pinene, 3-carene, myrcene, and terpinolene were greater in ponderosa pine. Although we found differences both in quantitative and qualitative preformed oleoresin defenses, the ecological relevance of these differences to bark beetle susceptibility have not been fully tested.

  18. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host

    Directory of Open Access Journals (Sweden)

    Yingru eLiu

    2011-03-01

    Full Text Available It is well known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host’s immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory- immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine.

  19. Auxin promotes susceptibility to Pseudomonas syringae via a mechanism independent of suppression of salicylic acid-mediated defenses.

    Science.gov (United States)

    Mutka, Andrew M; Fawley, Stephen; Tsao, Tiffany; Kunkel, Barbara N

    2013-06-01

    Auxin is a key plant growth regulator that also impacts plant-pathogen interactions. Several lines of evidence suggest that the bacterial plant pathogen Pseudomonas syringae manipulates auxin physiology in Arabidopsis thaliana to promote pathogenesis. Pseudomonas syringae strategies to alter host auxin biology include synthesis of the auxin indole-3-acetic acid (IAA) and production of virulence factors that alter auxin responses in host cells. The application of exogenous auxin enhances disease caused by P. syringae strain DC3000. This is hypothesized to result from antagonism between auxin and salicylic acid (SA), a major regulator of plant defenses, but this hypothesis has not been tested in the context of infected plants. We further investigated the role of auxin during pathogenesis by examining the interaction of auxin and SA in the context of infection in plants with elevated endogenous levels of auxin. We demonstrated that elevated IAA biosynthesis in transgenic plants overexpressing the YUCCA 1 (YUC1) auxin biosynthesis gene led to enhanced susceptibility to DC3000. Elevated IAA levels did not interfere significantly with host defenses, as effector-triggered immunity was active in YUC1-overexpressing plants, and we observed only minor effects on SA levels and SA-mediated responses. Furthermore, a plant line carrying both the YUC1-overexpression transgene and the salicylic acid induction deficient 2 (sid2) mutation, which impairs SA synthesis, exhibited additive effects of enhanced susceptibility from both elevated auxin levels and impaired SA-mediated defenses. Thus, in IAA overproducing plants, the promotion of pathogen growth occurs independently of suppression of SA-mediated defenses. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

  20. Host niches and defensive extended phenotypes structure parasitoid wasp communities.

    Directory of Open Access Journals (Sweden)

    Richard Bailey

    2009-08-01

    Full Text Available Oak galls are spectacular extended phenotypes of gallwasp genes in host oak tissues and have evolved complex morphologies that serve, in part, to exclude parasitoid natural enemies.Parasitoids and their insect herbivore hosts have coevolved to produce diverse communities comprising about a third of all animal species. The factors structuring these communities, however, remain poorly understood. An emerging theme in community ecology is the need to consider the effects of host traits, shaped by both natural selection and phylogenetic history, on associated communities of natural enemies. Here we examine the impact of host traits and phylogenetic relatedness on 48 ecologically closed and species-rich communities of parasitoids attacking gall-inducing wasps on oaks. Gallwasps induce the development of spectacular and structurally complex galls whose species- and generation-specific morphologies are the extended phenotypes of gallwasp genes. All the associated natural enemies attack their concealed hosts through gall tissues, and several structural gall traits have been shown to enhance defence against parasitoid attack. Here we explore the significance of these and other host traits in predicting variation in parasitoid community structure across gallwasp species. In particular, we test the "Enemy Hypothesis," which predicts that galls with similar morphology will exclude similar sets of parasitoids and therefore have similar parasitoid communities. Having controlled for phylogenetic patterning in host traits and communities, we found significant correlations between parasitoid community structure and several gall structural traits (toughness, hairiness, stickiness, supporting the Enemy Hypothesis. Parasitoid community structure was also consistently predicted by components of the hosts' spatiotemporal niche, particularly host oak taxonomy and gall location (e.g., leaf versus bud versus seed. The combined explanatory power of structural and

  1. Host Niches and Defensive Extended Phenotypes Structure Parasitoid Wasp Communities

    Science.gov (United States)

    Bailey, Richard; Schönrogge, Karsten; Cook, James M.; Melika, George; Csóka, György; Thuróczy, Csaba; Stone, Graham N.

    2009-01-01

    Oak galls are spectacular extended phenotypes of gallwasp genes in host oak tissues and have evolved complex morphologies that serve, in part, to exclude parasitoid natural enemies. Parasitoids and their insect herbivore hosts have coevolved to produce diverse communities comprising about a third of all animal species. The factors structuring these communities, however, remain poorly understood. An emerging theme in community ecology is the need to consider the effects of host traits, shaped by both natural selection and phylogenetic history, on associated communities of natural enemies. Here we examine the impact of host traits and phylogenetic relatedness on 48 ecologically closed and species-rich communities of parasitoids attacking gall-inducing wasps on oaks. Gallwasps induce the development of spectacular and structurally complex galls whose species- and generation-specific morphologies are the extended phenotypes of gallwasp genes. All the associated natural enemies attack their concealed hosts through gall tissues, and several structural gall traits have been shown to enhance defence against parasitoid attack. Here we explore the significance of these and other host traits in predicting variation in parasitoid community structure across gallwasp species. In particular, we test the “Enemy Hypothesis,” which predicts that galls with similar morphology will exclude similar sets of parasitoids and therefore have similar parasitoid communities. Having controlled for phylogenetic patterning in host traits and communities, we found significant correlations between parasitoid community structure and several gall structural traits (toughness, hairiness, stickiness), supporting the Enemy Hypothesis. Parasitoid community structure was also consistently predicted by components of the hosts' spatiotemporal niche, particularly host oak taxonomy and gall location (e.g., leaf versus bud versus seed). The combined explanatory power of structural and spatiotemporal

  2. Peripheral and central mediators of lipopolysaccharide induced suppression of defensive rage behavior in the cat.

    Science.gov (United States)

    Bhatt, S; Bhatt, R S; Zalcman, S S; Siegel, A

    2009-11-10

    Based upon recent findings in our laboratory that cytokines microinjected into the medial hypothalamus or periaqueductal gray (PAG) powerfully modulate defensive rage behavior in cat, the present study determined the effects of peripherally released cytokines following lipopolysaccharide (LPS) challenge upon defensive rage. The study involved initial identification of the effects of peripheral administration of LPS upon defensive rage by electrical stimulation from PAG and subsequent determination of the peripheral and central mechanisms governing this process. The results revealed significant elevation in response latencies for defensive rage from 60 to 300 min, post LPS injection, with no detectable signs of sickness behavior present at 60 min. In contrast, head turning behavior elicited by stimulation of adjoining midbrain sites was not affected by LPS administration, suggesting a specificity of the effects of LPS upon defensive rage. Direct administration of LPS into the medial hypothalamus had no effect on defensive rage, suggesting that the effects of LPS were mediated by peripheral cytokines rather than by any direct actions upon hypothalamic neurons. Complete blockade of the suppressive effects of LPS by peripheral pretreatment with an Anti-tumor necrosis factor-alpha (TNFalpha) antibody but not with an anti- interleukin-1 (IL-1) antibody demonstrated that the effects of LPS were mediated through TNF-alpha rather than through an IL-1 mechanism. A determination of the central mechanisms governing LPS suppression revealed that pretreatment of the medial hypothalamus with PGE(2) or 5-HT(1A) receptor antagonists each completely blocked the suppressive effects of LPS, while microinjections of a TNF-alpha antibody into the medial hypothalamus were ineffective. Microinjections of -Iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) benzamide monohydrochloride (p-MPPI) into lateral hypothalamus (to test for anatomical specificity) had no effect upon

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

    Science.gov (United States)

    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

  4. Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.

    Directory of Open Access Journals (Sweden)

    David Proud

    Full Text Available Human rhinovirus (HRV infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

  5. Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.

    Science.gov (United States)

    Proud, David; Hudy, Magdalena H; Wiehler, Shahina; Zaheer, Raza S; Amin, Minaa A; Pelikan, Jonathan B; Tacon, Claire E; Tonsaker, Tabitha O; Walker, Brandie L; Kooi, Cora; Traves, Suzanne L; Leigh, Richard

    2012-01-01

    Human rhinovirus (HRV) infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD) and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE) modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

  6. A host defense mechanism involving CFTR-mediated bicarbonate secretion in bacterial prostatitis.

    Directory of Open Access Journals (Sweden)

    Chen Xie

    Full Text Available BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(- and HCO(3(-, in mediating prostate HCO(3(- secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II, along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3(- content (>50 mM, rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3(- on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3(- secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3(- secretion may be up-regulated in prostatitis as a host defense mechanism.

  7. Host defenses against bacterial pore-forming toxins

    NARCIS (Netherlands)

    Los, F.C.O.

    2011-01-01

    Pore-forming toxins (PFTs), the most common bacterial toxins, contribute to infection by perforating host cell membranes. Excessive use and lack of new development of antibiotics are causing increasing numbers of drug-resistant bacteria, like methicillin-resistant Staphylococcus aureus (MRSA) and

  8. Modification of FMDV anti-host defense mechanism

    DEFF Research Database (Denmark)

    Guan, Suhua; Belsham, Graham

    Foot-and-mouth disease virus (FMDV) is the etiologic agent of FMD, an infectious and sometimes fatal viral disease that affects cloven-hoofed animals. The FMDV genome encodes a large polyprotein, the first component of which is the Leader protein. Unusually, within the picornavirus family, the FMDV...... Leader protein (Lpro) is a protease. This protease induces a very rapid inhibition of host cell cap-dependent protein synthesis within infected cells. This results from cleavage of the cellular translation initiation factor eIF4G. Translation of the viral RNA is unaffected since it is dependent...... allow design of mutant viruses that are deficient in blocking host cell responses to infection (e.g. interferon induction) and assist in the rational design of antiviral agents targeting this process....

  9. Unmasking host and microbial strategies in the Agrobacterium-plant defense tango

    Directory of Open Access Journals (Sweden)

    Elizabeth E. Hwang

    2015-03-01

    Full Text Available Coevolutionary forces drive adaptation of both plant-associated microbes and their hosts. Eloquently captured in the Red Queen Hypothesis, the complexity of each plant-pathogen relationship reflects escalating adversarial strategies, but also external biotic and abiotic pressures on both partners. Innate immune responses are triggered by highly conserved pathogen-associated molecular patterns, or PAMPs, that are harbingers of microbial presence. Upon cell surface receptor-mediated recognition of these pathogen-derived molecules, host plants mount a variety of physiological responses to limit pathogen survival and/or invasion. Successful pathogens often rely on secretion systems to translocate host-modulating effectors that subvert plant defenses, thereby increasing virulence. Host plants, in turn, have evolved to recognize these effectors, activating what has typically been characterized as a pathogen-specific form of immunity. Recent data support the notion that PAMP-triggered and effector-triggered defenses are complementary facets of a convergent, albeit differentially regulated, set of immune responses. This review highlights the key players in the plant’s recognition and signal transduction pathways, with a focus on the aspects that may limit Agrobacterium tumefaciens infection and the ways it might overcome those defenses. Recent advances in the field include a growing appreciation for the contributions of cytoskeletal dynamics and membrane trafficking to the regulation of these exquisitely tuned defenses. Pathogen counter-defenses frequently manipulate the interwoven hormonal pathways that mediate host responses. Emerging systems-level analyses include host physiological factors such as circadian cycling. The existing literature indicates that varying or even conflicting results from different labs may well be attributable to environmental factors including time of day of infection, temperature, and/or developmental stage of the host

  10. Epigenetic silencing of host cell defense genes enhances intracellular survival of the rickettsial pathogen Anaplasma phagocytophilum.

    Directory of Open Access Journals (Sweden)

    Jose C Garcia-Garcia

    2009-06-01

    Full Text Available Intracellular bacteria have evolved mechanisms that promote survival within hostile host environments, often resulting in functional dysregulation and disease. Using the Anaplasma phagocytophilum-infected granulocyte model, we establish a link between host chromatin modifications, defense gene transcription and intracellular bacterial infection. Infection of THP-1 cells with A. phagocytophilum led to silencing of host defense gene expression. Histone deacetylase 1 (HDAC1 expression, activity and binding to the defense gene promoters significantly increased during infection, which resulted in decreased histone H3 acetylation in infected cells. HDAC1 overexpression enhanced infection, whereas pharmacologic and siRNA HDAC1 inhibition significantly decreased bacterial load. HDAC2 does not seem to be involved, since HDAC2 silencing by siRNA had no effect on A. phagocytophilum intracellular propagation. These data indicate that HDAC up-regulation and epigenetic silencing of host cell defense genes is required for A. phagocytophilum infection. Bacterial epigenetic regulation of host cell gene transcription could be a general mechanism that enhances intracellular pathogen survival while altering cell function and promoting disease.

  11. Albugo-imposed changes to tryptophan-derived antimicrobial metabolite biosynthesis may contribute to suppression of non-host resistance to Phytophthora infestans in Arabidopsis thaliana.

    Science.gov (United States)

    Prince, David C; Rallapalli, Ghanasyam; Xu, Deyang; Schoonbeek, Henk-Jan; Çevik, Volkan; Asai, Shuta; Kemen, Eric; Cruz-Mireles, Neftaly; Kemen, Ariane; Belhaj, Khaoula; Schornack, Sebastian; Kamoun, Sophien; Holub, Eric B; Halkier, Barbara A; Jones, Jonathan D G

    2017-03-20

    Plants are exposed to diverse pathogens and pests, yet most plants are resistant to most plant pathogens. Non-host resistance describes the ability of all members of a plant species to successfully prevent colonization by any given member of a pathogen species. White blister rust caused by Albugo species can overcome non-host resistance and enable secondary infection and reproduction of usually non-virulent pathogens, including the potato late blight pathogen Phytophthora infestans on Arabidopsis thaliana. However, the molecular basis of host defense suppression in this complex plant-microbe interaction is unclear. Here, we investigate specific defense mechanisms in Arabidopsis that are suppressed by Albugo infection. Gene expression profiling revealed that two species of Albugo upregulate genes associated with tryptophan-derived antimicrobial metabolites in Arabidopsis. Albugo laibachii-infected tissue has altered levels of these metabolites, with lower indol-3-yl methylglucosinolate and higher camalexin accumulation than uninfected tissue. We investigated the contribution of these Albugo-imposed phenotypes to suppression of non-host resistance to P. infestans. Absence of tryptophan-derived antimicrobial compounds enables P. infestans colonization of Arabidopsis, although to a lesser extent than Albugo-infected tissue. A. laibachii also suppresses a subset of genes regulated by salicylic acid; however, salicylic acid plays only a minor role in non-host resistance to P. infestans. Albugo sp. alter tryptophan-derived metabolites and suppress elements of the responses to salicylic acid in Arabidopsis. Albugo sp. imposed alterations in tryptophan-derived metabolites may play a role in Arabidopsis non-host resistance to P. infestans. Understanding the basis of non-host resistance to pathogens such as P. infestans could assist in development of strategies to elevate food security.

  12. Cdc42 promotes host defenses against fatal infection

    DEFF Research Database (Denmark)

    Lee, Keunwook; Boyd, Kelli L; Parekh, Diptiben V

    2013-01-01

    attempted to specifically delete it in these cells by crossing the Cdc42(fl/fl) mouse with a FSP-1 cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP-1cre;Cdc42(fl/fl) mice died at 3 weeks of age due to overwhelming suppurative upper airway infections...... showed that in addition to fibroblasts, the FSP-1 cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this non-specific cre mouse we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate...

  13. Too much of a good thing: How modulating LTB4actions restore host defense in homeostasis or disease.

    Science.gov (United States)

    Brandt, Stephanie L; Serezani, C Henrique

    2017-10-01

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

  14. Complement factor H in host defense and immune evasion.

    Science.gov (United States)

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

    2017-05-01

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

  15. Seneca Valley Virus Suppresses Host Type I Interferon Production by Targeting Adaptor Proteins MAVS, TRIF, and TANK for Cleavage.

    Science.gov (United States)

    Qian, Suhong; Fan, Wenchun; Liu, Tingting; Wu, Mengge; Zhang, Huawei; Cui, Xiaofang; Zhou, Yun; Hu, Junjie; Wei, Shaozhong; Chen, Huanchun; Li, Xiangmin; Qian, Ping

    2017-08-15

    Seneca Valley virus (SVV) is an oncolytic RNA virus belonging to the Picornaviridae family. Its nucleotide sequence is highly similar to those of members of the Cardiovirus genus. SVV is also a neuroendocrine cancer-selective oncolytic picornavirus that can be used for anticancer therapy. However, the interaction between SVV and its host is yet to be fully characterized. In this study, SVV inhibited antiviral type I interferon (IFN) responses by targeting different host adaptors, including mitochondrial antiviral signaling (MAVS), Toll/interleukin 1 (IL-1) receptor domain-containing adaptor inducing IFN-β (TRIF), and TRAF family member-associated NF-κB activator (TANK), via viral 3C protease (3C pro ). SVV 3C pro mediated the cleavage of MAVS, TRIF, and TANK at specific sites, which required its protease activity. The cleaved MAVS, TRIF, and TANK lost the ability to regulate pattern recognition receptor (PRR)-mediated IFN production. The cleavage of TANK also facilitated TRAF6-induced NF-κB activation. SVV was also found to be sensitive to IFN-β. Therefore, SVV suppressed antiviral IFN production to escape host antiviral innate immune responses by cleaving host adaptor molecules. IMPORTANCE Host cells have developed various defenses against microbial pathogen infection. The production of IFN is the first line of defense against microbial infection. However, viruses have evolved many strategies to disrupt this host defense. SVV, a member of the Picornavirus genus, is an oncolytic virus that shows potential functions in anticancer therapy. It has been demonstrated that IFN can be used in anticancer therapy for certain tumors. However, the relationship between oncolytic virus and innate immune response in anticancer therapy is still not well known. In this study, we showed that SVV has evolved as an effective mechanism to inhibit host type I IFN production by using its 3C pro to cleave the molecules MAVS, TRIF, and TANK directly. These molecules are crucial for

  16. Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense.

    NARCIS (Netherlands)

    Vos, J.B.; Sterkenburg, M.A. van; Rabe, K.F.; Schalkwijk, J.; Hiemstra, P.S.; Datson, N.A.

    2005-01-01

    The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or

  17. ST2 deficient mice display a normal host defense against pulmonary infection with Mycobacterium tuberculosis

    NARCIS (Netherlands)

    Wieland, Catharina W.; van der Windt, Gerritje J. W.; Florquin, Sandrine; McKenzie, Andrew N. J.; van der Poll, Tom

    2009-01-01

    Tuberculosis, caused by Mycobacterium (M.) tuberculosis, is a devastating infectious disease causing many deaths world-wide every year. Successful host defense mainly depends on a strong Th type I response. We investigated the role of T1/ST2 (recently identified as the receptor for IL-33), a typical

  18. The interferon response circuit in antiviral host defense.

    Science.gov (United States)

    Haller, O; Weber, F

    2009-01-01

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

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

    Science.gov (United States)

    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

  20. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis.

    Directory of Open Access Journals (Sweden)

    Mathieu Blanc

    2011-03-01

    transcription level. The reduction in srebf2 gene transcription upon infection and IFN treatment is also found to be strictly dependent on ifnar1. Altogether these results show that type 1 IFN signaling is both necessary and sufficient for reducing the sterol metabolic network activity upon infection, thereby linking the regulation of the sterol pathway with interferon anti-viral defense responses. These findings bring a new link between sterol metabolism and interferon antiviral response and support the idea of using host metabolic modifiers of innate immunity as a potential antiviral strategy.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  3. The Xanthomonas Type III Effector XopD Targets the Arabidopsis Transcription Factor MYB30 to Suppress Plant Defense[W

    Science.gov (United States)

    Canonne, Joanne; Marino, Daniel; Jauneau, Alain; Pouzet, Cécile; Brière, Christian; Roby, Dominique; Rivas, Susana

    2011-01-01

    Plant and animal pathogens inject type III effectors (T3Es) into host cells to suppress host immunity and promote successful infection. XopD, a T3E from Xanthomonas campestris pv vesicatoria, has been proposed to promote bacterial growth by targeting plant transcription factors and/or regulators. Here, we show that XopD from the B100 strain of X. campestris pv campestris is able to target MYB30, a transcription factor that positively regulates Arabidopsis thaliana defense and associated cell death responses to bacteria through transcriptional activation of genes related to very-long-chain fatty acid (VLCFA) metabolism. XopD specifically interacts with MYB30, resulting in inhibition of the transcriptional activation of MYB30 VLCFA-related target genes and suppression of Arabidopsis defense. The helix-loop-helix domain of XopD is necessary and sufficient to mediate these effects. These results illustrate an original strategy developed by Xanthomonas to subvert plant defense and promote development of disease. PMID:21917550

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

    Science.gov (United States)

    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.

  5. β2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Weinberger Andrew R

    2010-05-01

    Full Text Available Abstract Background Airway epithelial cells are critical in host defense against bacteria including Mycoplasma pneumoniae (Mp in chronic obstructive pulmonary disease (COPD and asthma. β2-agonists are mainstay of COPD and asthma therapy, but whether β2-agonists directly affect airway epithelial host defense functions is unclear. Methods Epithelial cells from bronchial brushings of normal (n = 8, asthma (n = 8 and COPD (n = 8 subjects were grown in air-liquid interface cultures, and treated with cigarette smoke extract (CSE and/or Th2 cytokine IL-13, followed by Mp infection and treatment with β2-agonists albuterol and formoterol for up to seven days. Mp and host defense proteins short palate, lung, and nasal epithelial clone 1 (SPLUNC1 and β-defensin-2 were quantified. Expression of β2-adrenergic receptors was also measured by real-time quantitative RT-PCR. Results (R- or racemic albuterol and (R,R- or racemic formoterol significantly decreased Mp levels in normal and asthma epithelial cells. Normal cells treated with Mp and (R- or racemic albuterol showed an increase in SPLUNC1, but not in β-defensin-2. COPD cells did not respond to drug treatment with a significant decrease in Mp or an increase in SPLUNC1. IL-13 attenuated drug effects on Mp, and markedly decreased SPLUNC1 and β2-adrenergic receptors. Conclusions These results for the first time show that β2-agonists enhance host defense functions of primary bronchial epithelial cells from normal and asthma subjects, which is attenuated by IL-13.

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

    Science.gov (United States)

    Lima, Tatiane S; Gov, Lanny; Lodoen, Melissa B

    2018-02-13

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

  7. Toxoplasma gondii GRA7-Targeted ASC and PLD1 Promote Antibacterial Host Defense via PKCα.

    Directory of Open Access Journals (Sweden)

    Hyun-Jung Koh

    2017-01-01

    Full Text Available Tuberculosis is a global health problem and at least one-third of the world's population is infected with Mycobacterium tuberculosis (MTB. MTB is a successful pathogen that enhances its own intracellular survival by inhibiting inflammation and arresting phago-lysosomal fusion. We previously demonstrated that Toxoplasma gondii (T. gondii dense granule antigen (GRA 7 interacts with TNF receptor-associated factor 6 via Myeloid differentiation primary response gene 88, enabling innate immune responses in macrophages. To extend these studies, we found that GRA7 interacts with host proteins involved in antimicrobial host defense mechanisms as a therapeutic strategy for tuberculosis. Here, we show that protein kinase C (PKCα-mediated phosphorylation of T. gondii GRA7-I (Ser52 regulates the interaction of GRA7 with PYD domain of apoptosis-associated speck-like protein containing a carboxy-terminal CARD, which is capable of oligomerization and inflammasome activation can lead to antimicrobial defense against MTB. Furthermore, GRA7-III interacted with the PX domain of phospholipase D1, facilitating its enzyme activity, phago-lysosomal maturation, and subsequent antimicrobial activity in a GRA7-III (Ser135 phosphorylation-dependent manner via PKCα. Taken together, these results underscore a previously unrecognized role of GRA7 in modulating antimicrobial host defense mechanism during mycobacterial infection.

  8. Learning from host-defense peptides: cationic, amphipathic peptoids with potent anticancer activity.

    Directory of Open Access Journals (Sweden)

    Wei Huang

    Full Text Available Cationic, amphipathic host defense peptides represent a promising group of agents to be developed for anticancer applications. Poly-N-substituted glycines, or peptoids, are a class of biostable, peptidomimetic scaffold that can display a great diversity of side chains in highly tunable sequences via facile solid-phase synthesis. Herein, we present a library of anti-proliferative peptoids that mimics the cationic, amphipathic structural feature of the host defense peptides and explore the relationships between the structure, anticancer activity and selectivity of these peptoids. Several peptoids are found to be potent against a broad range of cancer cell lines at low-micromolar concentrations including cancer cells with multidrug resistance (MDR, causing cytotoxicity in a concentration-dependent manner. They can penetrate into cells, but their cytotoxicity primarily involves plasma membrane perturbations. Furthermore, peptoid 1, the most potent peptoid synthesized, significantly inhibited tumor growth in a human breast cancer xenotransplantation model without any noticeable acute adverse effects in mice. Taken together, our work provided important structural information for designing host defense peptides or their mimics for anticancer applications. Several cationic, amphipathic peptoids are very attractive for further development due to their high solubility, stability against protease degradation, their broad, potent cytotoxicity against cancer cells and their ability to overcome multidrug resistance.

  9. Disruption of Ethylene Responses by Turnip mosaic virus Mediates Suppression of Plant Defense against the Green Peach Aphid Vector.

    Science.gov (United States)

    Casteel, Clare L; De Alwis, Manori; Bak, Aurélie; Dong, Haili; Whitham, Steven A; Jander, Georg

    2015-09-01

    Plants employ diverse responses mediated by phytohormones to defend themselves against pathogens and herbivores. Adapted pathogens and herbivores often manipulate these responses to their benefit. Previously, we demonstrated that Turnip mosaic virus (TuMV) infection suppresses callose deposition, an important plant defense induced in response to feeding by its aphid vector, the green peach aphid (Myzus persicae), and increases aphid fecundity compared with uninfected control plants. Further, we determined that production of a single TuMV protein, Nuclear Inclusion a-Protease (NIa-Pro) domain, was responsible for changes in host plant physiology and increased green peach aphid reproduction. To characterize the underlying molecular mechanisms of this phenomenon, we examined the role of three phytohormone signaling pathways, jasmonic acid, salicylic acid, and ethylene (ET), in TuMV-infected Arabidopsis (Arabidopsis thaliana), with or without aphid herbivory. Experiments with Arabidopsis mutants ethylene insensitive2 and ethylene response1, and chemical inhibitors of ET synthesis and perception (aminoethoxyvinyl-glycine and 1-methylcyclopropene, respectively), show that the ET signaling pathway is required for TuMV-mediated suppression of Arabidopsis resistance to the green peach aphid. Additionally, transgenic expression of NIa-Pro in Arabidopsis alters ET responses and suppresses aphid-induced callose formation in an ET-dependent manner. Thus, disruption of ET responses in plants is an additional function of NIa-Pro, a highly conserved potyvirus protein. Virus-induced changes in ET responses may mediate vector-plant interactions more broadly and thus represent a conserved mechanism for increasing transmission by insect vectors across generations. © 2015 American Society of Plant Biologists. All Rights Reserved.

  10. Shigella infection of intestinal epithelium and circumvention of the host innate defense system.

    Science.gov (United States)

    Ashida, Hiroshi; Ogawa, Michinaga; Mimuro, Hitomi; Sasakawa, Chihiro

    2009-01-01

    Shigella, Gram-negative bacteria closely related to Escherichia coli, are highly adapted human pathogens that cause bacillary dysentery. Although Shigella have neither adherence factors nor flagella required for attaching or accessing the intestinal epithelium, Shigella are capable of colonizing the intestinal epithelium by exploiting epithelial-cell functions and circumventing the host innate immune response. During Shigella infection, they deliver many numbers of effectors through the type III secretion system into the surrounding space and directly into the host-cell cytoplasm. The effectors play pivotal roles from the onset of bacterial infection through to the establishment of the colonization of the intestinal epithelium, such as bacterial invasion, intracellular survival, subversion of the host immune defense response, and maintenance of the infectious foothold. These examples suggest that Shigella have evolved highly sophisticated infectious and intracellular strategies to establish replicative niches in the intestinal epithelium.

  11. Exploring the interrelationship between alexithymia, defense style, emotional suppression, homicide-related posttraumatic stress disorder and psychiatric co-morbidity.

    Science.gov (United States)

    Chung, Man Cheung; Di, Xiaohu; Wan, King Hung

    2016-09-30

    This study investigated the interrelationship between alexithymia, defense style, emotional suppression, posttraumatic stress disorder (PTSD) following homicide and psychiatric co-morbidity. One hundred and fifty male homicide perpetrators and 156 male perpetrators of non-violent crime completed the Posttraumatic Stress Diagnostic Scale (except for non-violent perpetrators), the General Health Questionnaire-28, the Defense Styles Questionnaire, the Courtauld Emotional Control Scale and the Toronto Alexithymia Scale-20. The results showed that 44% of homicide perpetrators met the criteria for PTSD. No significant differences were found between groups in alexithymia, defense style and psychiatric co-morbidity. Homicide perpetrators suppressed depression significantly more than the non-violent group. PLS analyses showed that alexithymia was significantly correlated with defense style. Defense styles were significantly correlated with emotional suppression which, in turn, was associated with homicide-related PTSD and psychiatric co-morbidity. To conclude, perpetrators can experience PTSD reactions following the act of homicide. The severity of these reactions and other psychological problems were related to difficulty getting in touch with distressing emotions, the defenses they used to protect themselves psychologically and the way they suppressed their emotion. Copyright © 2016. Published by Elsevier Ireland Ltd.

  12. Suppression of RNA silencing by a plant DNA virus satellite requires a host calmodulin-like protein to repress RDR6 expression.

    Directory of Open Access Journals (Sweden)

    Fangfang Li

    2014-02-01

    Full Text Available 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

  13. Acute radiation syndrome (ARS – treatment of the reduced host defense

    Directory of Open Access Journals (Sweden)

    Heslet L

    2012-01-01

    Full Text Available Lars Heslet1, Christiane Bay2, Steen Nepper-Christensen31Serendex ApS, Gentofte; 2University of Copenhagen, Medical Faculty, Copenhagen; 3Department of Head and Neck Surgery, Otorhinolaryngology, Køge University Hospital, Køge, DenmarkBackground: The current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS. The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF] in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes.Methods: Review of the current literature.Results: The lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage’s important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS.Recommendation: Preemptive treatment should be initiated after suspected exposure of a radiation dose of at least ~2 Gy by prompt dosing of 250–400 µg GM-CSF/m2 or 5 µg/kg G-CSF administered systemically and concomitant inhalation of

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. NLRC4 and TLR5 each contribute to host defense in respiratory melioidosis.

    Directory of Open Access Journals (Sweden)

    T Eoin West

    2014-09-01

    Full Text Available Burkholderia pseudomallei causes the tropical infection melioidosis. Pneumonia is a common manifestation of melioidosis and is associated with high mortality. Understanding the key elements of host defense is essential to developing new therapeutics for melioidosis. As a flagellated bacterium encoding type III secretion systems, B. pseudomallei may trigger numerous host pathogen recognition receptors. TLR5 is a flagellin sensor located on the plasma membrane. NLRC4, along with NAIP proteins, assembles a canonical caspase-1-dependent inflammasome in the cytoplasm that responds to flagellin (in mice and type III secretion system components (in mice and humans. In a murine model of respiratory melioidosis, Tlr5 and Nlrc4 each contributed to survival. Mice deficient in both Tlr5 and Nlrc4 were not more susceptible than single knockout animals. Deficiency of Casp1/Casp11 resulted in impaired bacterial control in the lung and spleen; in the lung much of this effect was attributable to Nlrc4, despite relative preservation of pulmonary IL-1β production in Nlrc4(-/- mice. Histologically, deficiency of Casp1/Casp11 imparted more severe pulmonary inflammation than deficiency of Nlrc4. The human NLRC4 region polymorphism rs6757121 was associated with survival in melioidosis patients with pulmonary involvement. Co-inheritance of rs6757121 and a functional TLR5 polymorphism had an additive effect on survival. Our results show that NLRC4 and TLR5, key components of two flagellin sensing pathways, each contribute to host defense in respiratory melioidosis.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-10-01

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

  19. Conventional NK cells can produce IL-22 and promote host defense in Klebsiella pneumoniae pneumonia.

    Science.gov (United States)

    Xu, Xin; Weiss, Ido D; Zhang, Hongwei H; Singh, Satya P; Wynn, Thomas A; Wilson, Mark S; Farber, Joshua M

    2014-02-15

    It was reported that host defense against pulmonary Klebsiella pneumoniae infection requires IL-22, which was proposed to be of T cell origin. Supporting a role for IL-22, we found that Il22(-/-) mice had decreased survival compared with wild-type mice after intratracheal infection with K. pneumoniae. Surprisingly, however, Rag2(-/-) mice did not differ from wild-type mice in survival or levels of IL-22 in the lungs postinfection with K. pneumoniae. In contrast, K. pneumoniae-infected Rag2(-/-)Il2rg(-/-) mice failed to produce IL-22. These data suggested a possible role for NK cells or other innate lymphoid cells in host defense and production of IL-22. Unlike NK cell-like innate lymphoid cells that produce IL-22 and display a surface phenotype of NK1.1(-)NKp46(+)CCR6(+), lung NK cells showed the conventional phenotype, NK1.1(+)NKp46(+)CCR6(-). Mice depleted of NK cells using anti-asialo GM1 showed decreased survival and higher lung bacterial counts, as well as increased dissemination of K. pneumoniae to blood and liver, compared with control-treated mice. NK cell depletion also led to decreased production of IL-22 in the lung. Within 1 d postinfection, although there was no increase in the number of lung NK cells, a subset of lung NK cells became competent to produce IL-22, and such cells were found in both wild-type and Rag2(-/-) mice. Our data suggest that, during pulmonary infection of mice with K. pneumoniae, conventional NK cells are required for optimal host defense, which includes the production of IL-22.

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

    Science.gov (United States)

    Radulovic, Marko; Godovac-Zimmermann, Jasminka

    2014-01-01

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

  1. Important role for Toll-like receptor 9 in host defense against meningococcal sepsis

    DEFF Research Database (Denmark)

    Sjölinder, Hong; Mogensen, Trine; Kilian, Mogens

    2008-01-01

    have been reported to be involved in the host response to N. meningitidis. While TLR4 has been suggested to play an important role in early containment of infection, the roles of TLR2 and TLR9 in meningococcal disease are not well described. Using a model for meningococcal sepsis, we report that TLR9...... by reduced production of nitric oxide by TLR9-deficient macrophages. Interestingly, TLR9(-/-) mice recruited more macrophages to the bloodstream than wild-type mice and produced elevated levels of cytokines at late time points during infection. At the cellular level, activation of signal transduction...... and induction of cytokine gene expression were independent of TLR2 or TLR9 in macrophages and conventional dendritic cells. In contrast, plasmacytoid dendritic cells relied entirely on TLR9 to induce these activities. Thus, our data demonstrate an important role for TLR9 in host defense against N. meningitidis....

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

    Science.gov (United States)

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

    2017-01-01

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

  3. Suppression of plant defenses by a Myzus persicae (green peach aphid) salivary effector protein.

    Science.gov (United States)

    Elzinga, Dezi A; De Vos, Martin; Jander, Georg

    2014-07-01

    The complex interactions between aphids and their host plant are species-specific and involve multiple layers of recognition and defense. Aphid salivary proteins, which are released into the plant during phloem feeding, are a likely mediator of these interactions. In an approach to identify aphid effectors that facilitate feeding from host plants, eleven Myzus persicae (green peach aphid) salivary proteins and the GroEL protein of Buchnera aphidicola, a bacterial endosymbiont of this aphid species, were expressed transiently in Nicotiana tabacum (tobacco). Whereas two salivary proteins increased aphid reproduction, expression of three other aphid proteins and GroEL significantly decreased aphid reproduction on N. tabacum. These effects were recapitulated in stable transgenic Arabidopsis thaliana plants. Further experiments with A. thaliana expressing Mp55, a salivary protein that increased aphid reproduction, showed lower accumulation of 4-methoxyindol-3-ylmethylglucosinolate, callose and hydrogen peroxide in response to aphid feeding. Mp55-expressing plants also were more attractive for aphids in choice assays. Silencing Mp55 gene expression in M. persicae using RNA interference approaches reduced aphid reproduction on N. tabacum, A. thaliana, and N. benthamiana. Together, these results demonstrate a role for Mp55, a protein with as-yet-unknown molecular function, in the interaction of M. persicae with its host plants.

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

    Science.gov (United States)

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

    2016-04-01

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

  5. Shedding light on the role of photosynthesis in pathogen colonization and host defense

    KAUST Repository

    Garavaglia, Betiana S.

    2010-09-01

    The role of photosynthesis in plant defense is a fundamental question awaiting further molecular and physiological elucidation. To this end we investigated host responses to infection with the bacterial pathogen Xanthomonas axonopodis pv. citri, the pathogen responsible for citrus canker. This pathogen encodes a plant-like natriuretic peptide (XacPNP) that is expressed specifically during the infection process and prevents deterioration of the physiological condition of the infected tissue. Proteomic assays of citrus leaves infected with a XacPNP deletion mutant (DeltaXacPNP) resulted in a major reduction in photosynthetic proteins such as Rubisco, Rubisco activase and ATP synthase as a compared with infection with wild type bacteria. In contrast, infiltration of citrus leaves with recombinant XacPNP caused an increase in these host proteins and a concomitant increase in photosynthetic efficiency as measured by chlorophyll fluorescence assays. Reversion of the reduction in photosynthetic efficiency in citrus leaves infected with DeltaXacPNP was achieved by the application of XacPNP or Citrus sinensis PNP lending support to a case of molecular mimicry. Finally, given that DeltaXacPNP infection is less successful than infection with the wild type, it appears that reducing photosynthesis is an effective plant defense mechanism against biotrophic pathogens.

  6. The Thrombin-Derived Host Defense Peptide GKY25 Inhibits Endotoxin-Induced Responses through Interactions with Lipopolysaccharide and Macrophages/Monocytes

    DEFF Research Database (Denmark)

    Hansen, Finja C; Kalle-Brune, Martina; van der Plas, Mariena J A

    2015-01-01

    Host defense peptides have recently gained much interest as novel anti-infectives owing to their ability to kill bacteria and simultaneously modulate host cell responses. The cationic host defense peptide GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE), derived from the C terminus of human thrombin, inhibits p...

  7. Immune responses against human papillomavirus (HPV) infection and evasion of host defense in cervical cancer.

    Science.gov (United States)

    Sasagawa, Toshiyuki; Takagi, Hiroaki; Makinoda, Satoru

    2012-12-01

    Human papillomavirus (HPV) is the most important etiological factor for cervical cancer. A recent study demonstrated that more than 20 HPV types were thought to be oncogenic for uterine cervical cancer. Notably, more than one-half of women show cervical HPV infections soon after their sexual debut, and about 90 % of such infections are cleared within 3 years. Immunity against HPV might be important for elimination of the virus. The innate immune responses involving macrophages, natural killer cells, and natural killer T cells may play a role in the first line of defense against HPV infection. In the second line of defense, adaptive immunity via cytotoxic T lymphocytes (CTLs) targeting HPV16 E2 and E6 proteins appears to eliminate cells infected with HPV16. However, HPV can evade host immune responses. First, HPV does not kill host cells during viral replication and therefore neither presents viral antigen nor induces inflammation. HPV16 E6 and E7 proteins downregulate the expression of type-1 interferons (IFNs) in host cells. The lack of co-stimulatory signals by inflammatory cytokines including IFNs during antigen recognition may induce immune tolerance rather than the appropriate responses. Moreover, HPV16 E5 protein downregulates the expression of HLA-class 1, and it facilitates evasion of CTL attack. These mechanisms of immune evasion may eventually support the establishment of persistent HPV infection, leading to the induction of cervical cancer. Considering such immunological events, prophylactic HPV16 and 18 vaccine appears to be the best way to prevent cervical cancer in women who are immunized in adolescence.

  8. Suppression of graft-versus-host reactivity by a single host-specific blood transfusion to prospective donors of hemopoietic cells

    NARCIS (Netherlands)

    Knulst, A.C.; Bril-Bazuin, C.; Savelkoul, H.F.J.; Benner, R.

    1991-01-01

    Delayed-type hypersensitivity responses against recipient's histocompatibility antigens can occur early in the course of a graft-versus-host reaction in lethally irradiated allogeneically reconstituted mice. This reactivity could be suppressed by a single host-specific blood transfusion to the

  9. Host-microbe interactions and defense mechanisms in the development of amoebic liver abscesses.

    Science.gov (United States)

    Santi-Rocca, Julien; Rigothier, Marie-Christine; Guillén, Nancy

    2009-01-01

    Amoebiasis by Entamoeba histolytica is a major public health problem in developing countries and leads to several thousand deaths per year. The parasite invades the intestine (provoking diarrhea and dysentery) and the liver, where it forms abscesses (amoebic liver abscesses [ALAs]). The liver is the organ responsible for filtering blood coming from the intestinal tract, a task that implies a particular structure and immune features. Amoebae use the portal route and break through the sinusoidal endothelial barrier to reach the hepatic parenchyma. When faced with systemic and cell-mediated defenses, trophozoites adapt to their new environment and modulate host responses, leading to parasite survival and the formation of inflammatory foci. Cytopathogenic effects and the onset of inflammation may be caused by diffusible products originating from parasites and/or immune cells either by their secretion or by their release after cell death. Liver infection thus results from the interplay between E. histolytica and hepatic cells. Despite its importance in terms of public health burden, the lack of integrated data on ALA genesis means that we have only an incomplete description of the initiation and development of hepatic amoebiasis. Here, we review the main steps of ALA development as well as the responses triggered in both the host and the parasite. Transcriptome studies highlighted parasite factors involved in adherence to human cells, cytopathogenic effects, and adaptative and stress responses. An understanding of their role in ALA development will help to unravel the host-pathogen interactions and their evolution throughout the infection.

  10. Virus-mediated suppression of host non-self recognition facilitates horizontal transmission of heterologous viruses.

    Directory of Open Access Journals (Sweden)

    Songsong Wu

    2017-03-01

    Full Text Available Non-self recognition is a common phenomenon among organisms; it often leads to innate immunity to prevent the invasion of parasites and maintain the genetic polymorphism of organisms. Fungal vegetative incompatibility is a type of non-self recognition which often induces programmed cell death (PCD and restricts the spread of molecular parasites. It is not clearly known whether virus infection could attenuate non-self recognition among host individuals to facilitate its spread. Here, we report that a hypovirulence-associated mycoreovirus, named Sclerotinia sclerotiorum mycoreovirus 4 (SsMYRV4, could suppress host non-self recognition and facilitate horizontal transmission of heterologous viruses. We found that cell death in intermingled colony regions between SsMYRV4-infected Sclerotinia sclerotiorum strain and other tested vegetatively incompatible strains was markedly reduced and inhibition barrage lines were not clearly observed. Vegetative incompatibility, which involves Heterotrimeric guanine nucleotide-binding proteins (G proteins signaling pathway, is controlled by specific loci termed het (heterokaryon incompatibility loci. Reactive oxygen species (ROS plays a key role in vegetative incompatibility-mediated PCD. The expression of G protein subunit genes, het genes, and ROS-related genes were significantly down-regulated, and cellular production of ROS was suppressed in the presence of SsMYRV4. Furthermore, SsMYRV4-infected strain could easily accept other viruses through hyphal contact and these viruses could be efficiently transmitted from SsMYRV4-infected strain to other vegetatively incompatible individuals. Thus, we concluded that SsMYRV4 is capable of suppressing host non-self recognition and facilitating heterologous viruses transmission among host individuals. These findings may enhance our understanding of virus ecology, and provide a potential strategy to utilize hypovirulence-associated mycoviruses to control fungal diseases.

  11. Exploration of Phage-Host Interactions in Fish Pathogen Vibrio anguillarum and Anti-Phage Defense Strategies

    DEFF Research Database (Denmark)

    Tan, Demeng

    of bacterial pathogenicity development. Therefore, successful application of phage therapy in the treatment of vibriosis requires a detailed understanding of phage-host interactions, especially with regards to anti-phage defense mechanisms in the host. Part I. As a first approach, 24 V. anguillarum and 13......T to repress ompK expression. It was demonstrated that QS controls the choice of anti-phage defense strategies in the V. anguillarum strain PF430-3, suggesting the presence of dynamic, temporary adaptations to phage infection pressure, while still securing the ability to produce a functional OmpK receptor....... In conclusion, this thesis provides a first insight into the dynamic vibriophage-host interactions, indicating the complexity of phage therapy in the treatment of vibriosis, regarding the evolution of anti-phage defense mechanisms, gene regulation, quorum sensing, biofilm formation, as well as pathogenesis...

  12. Are aphid parasitoids locally adapted to the prevalence of defensive symbionts in their hosts?

    Science.gov (United States)

    Vorburger, Christoph; Rouchet, Romain

    2016-12-12

    Insect parasitoids are under strong selection to overcome their hosts' defences. In aphids, resistance to parasitoids is largely determined by the presence or absence of protective endosymbionts such as Hamiltonella defensa. Hence, parasitoids may become locally adapted to the prevalence of this endosymbiont in their host populations. To address this, we collected isofemale lines of the aphid parasitoid Lysiphlebus fabarum from 17 sites in Switzerland and France, at which we also estimated the frequency of infection with H. defensa as well as other bacterial endosymbionts in five important aphid host species. The parasitoids' ability to overcome H. defensa-mediated resistance was then quantified by estimating their parasitism success on a single aphid clone (Aphis fabae fabae) that was either uninfected or experimentally infected with one of three different isolates of H. defensa. The five aphid species (Aphis fabae fabae, A. f. cirsiiacanthoides, A. hederae, A. ruborum, A. urticata) differed strongly in the relative frequencies of infection with different bacterial endosymbionts, but there was also geographic variation in symbiont prevalence. Specifically, the frequency of infection with H. defensa ranged from 22 to 47 % when averaged across species. Parasitoids from sites with a high prevalence of H. defensa tended to be more infective on aphids possessing H. defensa, but this relationship was not significant, thus providing no conclusive evidence that L. fabarum is locally adapted to the occurrence of H. defensa. On the other hand, we observed a strong interaction between parasitoid line and H. defensa isolate on parasitism success, indicative of a high specificity of symbiont-conferred resistance. This study is the first, to our knowledge, to test for local adaptation of parasitoids to the frequency of defensive symbionts in their hosts. While it yielded useful information on the occurrence of facultative endosymbionts in several important host species of L

  13. Cytosolic phospholipase A(2α and eicosanoids regulate expression of genes in macrophages involved in host defense and inflammation.

    Directory of Open Access Journals (Sweden)

    Saritha Suram

    Full Text Available The role of Group IVA cytosolic phospholipase A2 (cPLA2α activation in regulating macrophage transcriptional responses to Candida albicans infection was investigated. cPLA2α releases arachidonic acid for the production of eicosanoids. In mouse resident peritoneal macrophages, prostacyclin, prostaglandin E2 and leukotriene C4 were produced within minutes of C. albicans addition before cyclooxygenase 2 expression. The production of TNFα was lower in C. albicans-stimulated cPLA2α(+/+ than cPLA2α(-/- macrophages due to an autocrine effect of prostaglandins that increased cAMP to a greater extent in cPLA2α(+/+ than cPLA2α(-/- macrophages. For global insight, differential gene expression in C. albicans-stimulated cPLA2α(+/+ and cPLA2α(-/- macrophages (3 h was compared by microarray. cPLA2α(+/+ macrophages expressed 86 genes at lower levels and 181 genes at higher levels than cPLA2α(-/- macrophages (≥2-fold, p<0.05. Several pro-inflammatory genes were expressed at lower levels (Tnfα, Cx3cl1, Cd40, Ccl5, Csf1, Edn1, CxCr7, Irf1, Irf4, Akna, Ifnγ, several IFNγ-inducible GTPases. Genes that dampen inflammation (Socs3, Il10, Crem, Stat3, Thbd, Thbs1, Abca1 and genes involved in host defense (Gja1, Csf3, Trem1, Hdc were expressed at higher levels in cPLA2α(+/+ macrophages. Representative genes expressed lower in cPLA2α(+/+ macrophages (Tnfα, Csf1 were increased by treatment with a prostacyclin receptor antagonist and protein kinase A inhibitor, whereas genes expressed at higher levels (Crem, Nr4a2, Il10, Csf3 were suppressed. The results suggest that C. albicans stimulates an autocrine loop in macrophages involving cPLA2α, cyclooxygenase 1-derived prostaglandins and increased cAMP that globally effects expression of genes involved in host defense and inflammation.

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

    Directory of Open Access Journals (Sweden)

    Hao Li

    2016-06-01

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

  15. A link between blood coagulation and prophenol oxidase activation in arthropod host defense.

    Science.gov (United States)

    Nagai, T; Kawabata, S

    2000-09-22

    Phenol oxidase, a copper-containing enzyme, is widely distributed not only in animals but also in plants and fungi, which is responsible for initiating the biosynthesis of melanin. Activation of prophenol oxidase in arthropods is important in host defense. However, the prophenol oxidase-activating system remains poorly understood at the molecular level. Here we show that the coagulation cascade of the horseshoe crab Tachypleus tridentatus is linked to prophenol oxidase activation, with the oxygen carrier hemocyanin functioning as a substitute for prophenol oxidase. Tachypleus clotting enzyme functionally transforms hemocyanin to phenol oxidase, and the conversion reaches a plateau at 1:1 stoichiometry without proteolytic cleavage. The active site-masked clotting enzyme also has the same effect, suggesting that complex formation of the clotting enzyme with hemocyanin is critical for the conversion. The two systems of blood coagulation and prophenol oxidase activation may have evolved from a common ancestral protease cascade.

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

    Science.gov (United States)

    Herbert, B A; Novince, C M; Kirkwood, K L

    2016-06-01

    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 preclinical 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. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Derrick R Samuelson

    2017-06-01

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

  18. The multifunctional host defense peptide SPLUNC1 is critical for homeostasis of the mammalian upper airway.

    Directory of Open Access Journals (Sweden)

    Glen McGillivary

    2010-10-01

    Full Text Available Otitis media (OM is a highly prevalent pediatric disease caused by normal flora of the nasopharynx that ascend the Eustachian tube and enter the middle ear. As OM is a disease of opportunity, it is critical to gain an increased understanding of immune system components that are operational in the upper airway and aid in prevention of this disease. SPLUNC1 is an antimicrobial host defense peptide that is hypothesized to contribute to the health of the airway both through bactericidal and non-bactericidal mechanisms. We used small interfering RNA (siRNA technology to knock down expression of the chinchilla ortholog of human SPLUNC1 (cSPLUNC1 to begin to determine the role that this protein played in prevention of OM. We showed that knock down of cSPLUNC1 expression did not impact survival of nontypeable Haemophilus influenzae, a predominant causative agent of OM, in the chinchilla middle ear under the conditions tested. In contrast, expression of cSPLUNC1 was essential for maintenance of middle ear pressure and efficient mucociliary clearance, key defense mechanisms of the tubotympanum. Collectively, our data have provided the first in vivo evidence that cSPLUNC1 functions to maintain homeostasis of the upper airway and, thereby, is critical for protection of the middle ear.

  19. An Amphibian Host Defense Peptide Is Virucidal for Human H1 Hemagglutinin-Bearing Influenza Viruses.

    Science.gov (United States)

    Holthausen, David J; Lee, Song Hee; Kumar, Vineeth Tv; Bouvier, Nicole M; Krammer, Florian; Ellebedy, Ali H; Wrammert, Jens; Lowen, Anice C; George, Sanil; Pillai, Madhavan Radhakrishna; Jacob, Joshy

    2017-04-18

    Although vaccines confer protection against influenza A viruses, antiviral treatment becomes the first line of defense during pandemics because there is insufficient time to produce vaccines. Current antiviral drugs are susceptible to drug resistance, and developing new antivirals is essential. We studied host defense peptides from the skin of the South Indian frog and demonstrated that one of these, which we named "urumin," is virucidal for H1 hemagglutinin-bearing human influenza A viruses. This peptide specifically targeted the conserved stalk region of H1 hemagglutinin and was effective against drug-resistant H1 influenza viruses. Using electron microscopy, we showed that this peptide physically destroyed influenza virions. It also protected naive mice from lethal influenza infection. Urumin represents a unique class of anti-influenza virucide that specifically targets the hemagglutinin stalk region, similar to targeting of antibodies induced by universal influenza vaccines. Urumin therefore has the potential to contribute to first-line anti-viral treatments during influenza outbreaks. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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    Intan M. W. Dewi

    2017-10-01

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

  1. A proteomics perspective on viral DNA sensors in host defense and viral immune evasion mechanisms.

    Science.gov (United States)

    Crow, Marni S; Javitt, Aaron; Cristea, Ileana M

    2015-06-05

    The sensing of viral DNA is an essential step of cellular immune response to infections with DNA viruses. These human pathogens are spread worldwide, triggering a wide range of virus-induced diseases, and are associated with high levels of morbidity and mortality. Despite similarities between DNA molecules, mammalian cells have the remarkable ability to distinguish viral DNA from their own DNA. This detection is carried out by specialized antiviral proteins, called DNA sensors. These sensors bind to foreign DNA to activate downstream immune signaling pathways and alert neighboring cells by eliciting the expression of antiviral cytokines. The sensing of viral DNA was shown to occur both in the cytoplasm and in the nucleus of infected cells, disproving the notion that sensing occurred by simple spatial separation of viral and host DNA. A number of omic approaches, in particular, mass-spectrometry-based proteomic methods, have significantly contributed to the constantly evolving field of viral DNA sensing. Here, we review the impact of omic methods on the identification of viral DNA sensors, as well as on the characterization of mechanisms involved in host defense or viral immune evasion. Copyright © 2015. Published by Elsevier Ltd.

  2. Human host defense peptide LL-37 stimulates virulence factor production and adaptive resistance in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Nikola Strempel

    Full Text Available A multitude of different virulence factors as well as the ability to rapidly adapt to adverse environmental conditions are important features for the high pathogenicity of Pseudomonas aeruginosa. Both virulence and adaptive resistance are tightly controlled by a complex regulatory network and respond to external stimuli, such as host signals or antibiotic stress, in a highly specific manner. Here, we demonstrate that physiological concentrations of the human host defense peptide LL-37 promote virulence factor production as well as an adaptive resistance against fluoroquinolone and aminoglycoside antibiotics in P. aeruginosa PAO1. Microarray analyses of P. aeruginosa cells exposed to LL-37 revealed an upregulation of gene clusters involved in the production of quorum sensing molecules and secreted virulence factors (PQS, phenazine, hydrogen cyanide (HCN, elastase and rhamnolipids and in lipopolysaccharide (LPS modification as well as an induction of genes encoding multidrug efflux pumps MexCD-OprJ and MexGHI-OpmD. Accordingly, we detected significantly elevated levels of toxic metabolites and proteases in bacterial supernatants after LL-37 treatment. Pre-incubation of bacteria with LL-37 for 2 h led to a decreased susceptibility towards gentamicin and ciprofloxacin. Quantitative Realtime PCR results using a PAO1-pqsE mutant strain present evidence that the quinolone response protein and virulence regulator PqsE may be implicated in the regulation of the observed phenotype in response to LL-37. Further experiments with synthetic cationic antimicrobial peptides IDR-1018, 1037 and HHC-36 showed no induction of pqsE expression, suggesting a new role of PqsE as highly specific host stress sensor.

  3. Complement component C3 – The “Swiss Army Knife” of innate immunity and host defense

    NARCIS (Netherlands)

    Ricklin, Daniel; Reis, Edimara S.; Mastellos, Dimitrios C.; Gros, Piet; Lambris, John D.

    2016-01-01

    As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and

  4. The RIG-I-like helicase receptor MDA5 (IFIH1) is involved in the host defense against Candida infections

    NARCIS (Netherlands)

    Jaeger, M.; van der Lee, R.; Cheng, S-C.; Johnson, M. D.; Magadi Gopalaiah, Vinod Kumar; Ng, A.; Plantinga, T. S.; Smeekens, S. P.; Oosting, M.; Wang, X.; Barchet, W.; Fitzgerald, K.; Joosten, L. A. B.; Perfect, J. R.; Wijmenga, C.; van de Veerdonk, F. L.; Huynen, M. A.; Xavier, R. J.; Kullberg, B. J.; Netea, M. G.

    The induction of host defense against Candida species is initiated by recognition of the fungi by pattern recognition receptors and activation of downstream pathways that produce inflammatory mediators essential for infection clearance. In this study, we present complementary evidence based on

  5. Hematopoietic but not endothelial cell MyD88 contributes to host defense during gram-negative pneumonia derived sepsis

    NARCIS (Netherlands)

    van Lieshout, Miriam H. P.; Anas, Adam A.; Florquin, Sandrine; Hou, Baidong; van't Veer, Cornelis; de Vos, Alex F.; van der Poll, Tom

    2014-01-01

    Klebsiella pneumoniae is an important cause of sepsis. The common Toll-like receptor adapter myeloid differentiation primary response gene (MyD)88 is crucial for host defense against Klebsiella. Here we investigated the role of MyD88 in myeloid and endothelial cells during Klebsiella pneumosepsis.

  6. DMPD: The role of type I interferon production by dendritic cells in host defense. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17544561 The role of type I interferon production by dendritic cells in host defense. Fitzgerald-Bocars...fense. Authors Fitzgerald-Bocarsly P, Feng D. Publication Biochimie. 2007 Jun-Jul;89(6-7):843-55. Epub 2007

  7. Suppression of negative affect in cancer patients. Trauma and defensiveness of self-esteem as predictors of depression and anxiety

    Directory of Open Access Journals (Sweden)

    Fila-Jankowska Aleksandra

    2016-09-01

    Full Text Available The results of the work show that the relatively small differences in declared, negative emotional states (such as depression or anxiety between people suffering and not suffering from cancer can be explained by the suppression of negative affect in the former. It was assumed that the suppression is related to a compensation of an automatic, affective self-assessment - i.e. implicit self-esteem, lower in cancer patients. The results confirmed that the connection of cancer and depression (similarly cancer and anxiety became significantly stronger while the self-esteem defensiveness and past stress are statistically controlled.

  8. Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

    International Nuclear Information System (INIS)

    Svirshchevskaya, Elena V; Mariotti, Jacopo; Wright, Mollie H; Viskova, Natalia Y; Telford, William; Fowler, Daniel H; Varticovski, Lyuba

    2008-01-01

    Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice. Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation. Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses

  9. Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage.

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    Vengatesh Ganapathy

    Full Text Available Electronic cigarette (EC aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs.The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells.Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS and total antioxidant capacity (TAC were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively.EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1, an enzyme essential for the removal of oxidative DNA damage.Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public.

  10. Exploration of Phage-Host Interactions in Fish Pathogen Vibrio anguillarum and Anti-Phage Defense Strategies

    DEFF Research Database (Denmark)

    Tan, Demeng

    Vibrio sp. strains, representing considerable temporal (20 years) and geographic (9 countries) variation in regards to their origins of isolation, and 11 vibriophages representing three different families (Myoviridae, Siphoviridae, and Podoviridae), were characterized with respect host range, morphology...... of bacterial pathogenicity development. Therefore, successful application of phage therapy in the treatment of vibriosis requires a detailed understanding of phage-host interactions, especially with regards to anti-phage defense mechanisms in the host. Part I. As a first approach, 24 V. anguillarum and 13......, genome size and lytic properties. Together the host range of the 11 vibriophages covered all the 37 Vibrio strains in the collection. In addition, the occurrence of unique susceptibility patterns of the individual host isolates, as well as key phenotypic properties related to phage susceptibility...

  11. Identification of genetic loci required for Campylobacter resistance to fowlicidin-1, a chicken host defense peptide

    Directory of Open Access Journals (Sweden)

    Ky Van Hoang

    2012-03-01

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

  12. The Road from Host-Defense Peptides to a New Generation of Antimicrobial Drugs

    Directory of Open Access Journals (Sweden)

    Alicia Boto

    2018-02-01

    Full Text Available Host-defense peptides, also called antimicrobial peptides (AMPs, whose protective action has been used by animals for millions of years, fulfill many requirements of the pharmaceutical industry, such as: (1 broad spectrum of activity; (2 unlike classic antibiotics, they induce very little resistance; (3 they act synergically with conventional antibiotics; (4 they neutralize endotoxins and are active in animal models. However, it is considered that many natural peptides are not suitable for drug development due to stability and biodisponibility problems, or high production costs. This review describes the efforts to overcome these problems and develop new antimicrobial drugs from these peptides or inspired by them. The discovery process of natural AMPs is discussed, as well as the development of synthetic analogs with improved pharmacological properties. The production of these compounds at acceptable costs, using different chemical and biotechnological methods, is also commented. Once these challenges are overcome, a new generation of versatile, potent and long-lasting antimicrobial drugs is expected.

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

    Science.gov (United States)

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

    2014-01-01

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

  14. Perspectives for clinical use of engineered human host defense antimicrobial peptides.

    Science.gov (United States)

    Pachón-Ibáñez, María Eugenia; Smani, Younes; Pachón, Jerónimo; Sánchez-Céspedes, Javier

    2017-05-01

    Infectious diseases caused by bacteria, viruses or fungi are among the leading causes of death worldwide. The emergence of drug-resistance mechanisms, especially among bacteria, threatens the efficacy of all current antimicrobial agents, some of them already ineffective. As a result, there is an urgent need for new antimicrobial drugs. Host defense antimicrobial peptides (HDPs) are natural occurring and well-conserved peptides of innate immunity, broadly active against Gram-negative and Gram-positive bacteria, viruses and fungi. They also are able to exert immunomodulatory and adjuvant functions by acting as chemotactic for immune cells, and inducing cytokines and chemokines secretion. Moreover, they show low propensity to elicit microbial adaptation, probably because of their non-specific mechanism of action, and are able to neutralize exotoxins and endotoxins. HDPs have the potential to be a great source of novel antimicrobial agents. The goal of this review is to provide an overview of the advances made in the development of human defensins as well as the cathelicidin LL-37 and their derivatives as antimicrobial agents against bacteria, viruses and fungi for clinical use. © FEMS 2017.

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

    Science.gov (United States)

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

    2017-11-01

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

  16. Rapid host defense against Aspergillus fumigatus involves alveolar macrophages with a predominance of alternatively activated phenotype.

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    Shikha Bhatia

    Full Text Available The ubiquitous fungus Aspergillus fumigatus is associated with chronic diseases such as invasive pulmonary aspergillosis in immunosuppressed patients and allergic bronchopulmonary aspergillosis (ABPA in patients with cystic fibrosis or severe asthma. Because of constant exposure to this fungus, it is critical for the host to exercise an immediate and decisive immune response to clear fungal spores to ward off disease. In this study, we observed that rapidly after infection by A. fumigatus, alveolar macrophages predominantly express Arginase 1 (Arg1, a key marker of alternatively activated macrophages (AAMs. The macrophages were also found to express Ym1 and CD206 that are also expressed by AAMs but not NOS2, which is expressed by classically activated macrophages. The expression of Arg1 was reduced in the absence of the known signaling axis, IL-4Rα/STAT6, for AAM development. While both Dectin-1 and TLR expressed on the cell surface have been shown to sense A. fumigatus, fungus-induced Arg1 expression in CD11c(+ alveolar macrophages was not dependent on either Dectin-1 or the adaptor MyD88 that mediates intracellular signaling by most TLRs. Alveolar macrophages from WT mice efficiently phagocytosed fungal conidia, but those from mice deficient in Dectin-1 showed impaired fungal uptake. Depletion of macrophages with clodronate-filled liposomes increased fungal burden in infected mice. Collectively, our studies suggest that alveolar macrophages, which predominantly acquire an AAM phenotype following A. fumigatus infection, have a protective role in defense against this fungus.

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

    Science.gov (United States)

    Conlon, J. Michael; Mechkarska, Milena

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  19. Elevated Temperature and Drought Interact to Reduce Parasitoid Effectiveness in Suppressing Hosts

    Science.gov (United States)

    Romo, Cecilia M.; Tylianakis, Jason M.

    2013-01-01

    Climate change affects the abundance, distribution and activity of natural enemies that are important for suppressing herbivore crop pests. Moreover, higher mean temperatures and increased frequency of climatic extremes are expected to induce different responses across trophic levels, potentially disrupting predator-prey interactions. Using field observations, we examined the response of an aphid host-parasitoid system to variation in temperature. Temperature was positively associated with attack rates by parasitoids, but also with a non-significant trend towards increased attack rates by higher-level hyperparasitoids. Elevated hyperparasitism could partly offset any benefit of climate warming to parasitoids, and would suggest that higher trophic levels may hamper predictions of predator-prey interactions. Additionally, the mechanisms affecting host-parasitoid dynamics were examined using controlled laboratory experiments that simulated both temperature increase and drought. Parasitoid fitness and longevity responded differently when exposed to each climatic variable in isolation, compared to the interaction of both variables at once. Although temperature increase or drought tended to positively affect the ability of parasitoids to control aphid populations, these effects were significantly reversed when the drivers were expressed in concert. Additionally, separate warming and drought treatments reduced parasitoid longevity, and although temperature increased parasitoid emergence success and drought increased offspring production, combined temperature and drought produced the lowest parasitoid emergence. The non-additive effects of different climate drivers, combined with differing responses across trophic levels, suggest that predicting future pest outbreaks will be more challenging than previously imagined. PMID:23472147

  20. Elevated temperature and drought interact to reduce parasitoid effectiveness in suppressing hosts.

    Directory of Open Access Journals (Sweden)

    Cecilia M Romo

    Full Text Available Climate change affects the abundance, distribution and activity of natural enemies that are important for suppressing herbivore crop pests. Moreover, higher mean temperatures and increased frequency of climatic extremes are expected to induce different responses across trophic levels, potentially disrupting predator-prey interactions. Using field observations, we examined the response of an aphid host-parasitoid system to variation in temperature. Temperature was positively associated with attack rates by parasitoids, but also with a non-significant trend towards increased attack rates by higher-level hyperparasitoids. Elevated hyperparasitism could partly offset any benefit of climate warming to parasitoids, and would suggest that higher trophic levels may hamper predictions of predator-prey interactions. Additionally, the mechanisms affecting host-parasitoid dynamics were examined using controlled laboratory experiments that simulated both temperature increase and drought. Parasitoid fitness and longevity responded differently when exposed to each climatic variable in isolation, compared to the interaction of both variables at once. Although temperature increase or drought tended to positively affect the ability of parasitoids to control aphid populations, these effects were significantly reversed when the drivers were expressed in concert. Additionally, separate warming and drought treatments reduced parasitoid longevity, and although temperature increased parasitoid emergence success and drought increased offspring production, combined temperature and drought produced the lowest parasitoid emergence. The non-additive effects of different climate drivers, combined with differing responses across trophic levels, suggest that predicting future pest outbreaks will be more challenging than previously imagined.

  1. A Novel Meloidogyne incognita Effector Misp12 Suppresses Plant Defense Response at Latter Stages of Nematode Parasitism

    Science.gov (United States)

    Xie, Jialian; Li, Shaojun; Mo, Chenmi; Wang, Gaofeng; Xiao, Xueqiong; Xiao, Yannong

    2016-01-01

    Secreted effectors in plant root-knot nematodes (RKNs, or Meloidogyne spp.) play key roles in their parasite processes. Currently identified effectors mainly focus on the early stage of the nematode parasitism. There are only a few reports describing effectors that function in the latter stage. In this study, we identified a potential RKN effector gene, Misp12, that functioned during the latter stage of parasitism. Misp12 was unique in the Meloidogyne spp., and highly conserved in Meloidogyne incognita. It encoded a secretory protein that specifically expressed in the dorsal esophageal gland, and highly up-regulated during the female stages. Transient expression of Misp12-GUS-GFP in onion epidermal cell showed that Misp12 was localized in cytoplast. In addition, in planta RNA interference targeting Misp12 suppressed the expression of Misp12 in nematodes and attenuated parasitic ability of M. incognita. Furthermore, up-regulation of jasmonic acid (JA) and salicylic acid (SA) pathway defense-related genes in the virus-induced silencing of Misp12 plants, and down-regulation of SA pathway defense-related genes in Misp12-expressing plants indicated the gene might be associated with the suppression of the plant defense response. These results demonstrated that the novel nematode effector Misp12 played a critical role at latter parasitism of M. incognita. PMID:27446188

  2. Family matters: effect of host plant variation in chemical and mechanical defenses on a sequestering specialist herbivore.

    Science.gov (United States)

    Dimarco, Romina D; Nice, Chris C; Fordyce, James A

    2012-11-01

    Insect herbivores contend with various plant traits that are presumed to function as feeding deterrents. Paradoxically, some specialist insect herbivores might benefit from some of these plant traits, for example by sequestering plant chemical defenses that herbivores then use as their own defense against natural enemies. Larvae of the butterfly species Battus philenor (L.) (Papilionidae) sequester toxic alkaloids (aristolochic acids) from their Aristolochia host plants, rendering larvae and adults unpalatable to a broad range of predators. We studied the importance of two putative defensive traits in Aristolochia erecta: leaf toughness and aristolochic acid content, and we examined the effect of intra- and interplant chemical variation on the chemical phenotype of B. philenor larvae. It has been proposed that genetic variation for sequestration ability is "invisible to natural selection" because intra- and interindividual variation in host-plant chemistry will largely eliminate a role for herbivore genetic variation in determining an herbivore's chemical phenotype. We found substantial intra- and interplant variation in leaf toughness and in the aristolochic acid chemistry in A. erecta. Based on field observations and laboratory experiments, we showed that first-instar larvae preferentially fed on less tough, younger leaves and avoided tougher, older leaves, and we found no evidence that aristolochic acid content influenced first-instar larval foraging. We found that the majority of variation in the amount of aristolochic acid sequestered by larvae was explained by larval family, not by host-plant aristolochic acid content. Heritable variation for sequestration is the predominant determinant of larval, and likely adult, chemical phenotype. This study shows that for these highly specialized herbivores that sequester chemical defenses, traits that offer mechanical resistance, such as leaf toughness, might be more important determinants of early-instar larval

  3. Ficolins Promote Fungal Clearance in vivo and Modulate the Inflammatory Cytokine Response in Host Defense against Aspergillus fumigatus

    DEFF Research Database (Denmark)

    Genster, N; Cramer, E Præstekjær; Rosbjerg, A

    2016-01-01

    Aspergillus fumigatus is an opportunistic fungal pathogen that causes severe invasive infections in immunocompromised patients. Innate immunity plays a major role in protection against A. fumigatus. The ficolins are a family of soluble pattern recognition receptors that are capable of activating...... the lectin pathway of complement. Previous in vitro studies reported that ficolins bind to A. fumigatus, but their part in host defense against fungal infections in vivo is unknown. In this study, we used ficolin-deficient mice to investigate the role of ficolins during lung infection with A. fumigatus......-mediated complement activation in ficolin knockout mice and wild-type mice. In conclusion, this study demonstrates that ficolins are important in initial innate host defense against A. fumigatus infections in vivo....

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

    Directory of Open Access Journals (Sweden)

    Philipp Wiemann

    2017-05-01

    Full Text Available 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.

  5. Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense.

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    Philip O Scumpia

    2017-07-01

    Full Text Available Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs by pathogen recognition receptors (PRRs to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways contributing to the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, two PRR pathways-the Toll-like receptor (TLR and Stimulator of Interferon Gene (STING pathways-were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated a pro-inflammatory program while STING signaling activated an antiviral/type I interferon response with live but not killed S. aureus. This STING response was largely dependent on the cytosolic DNA sensor cyclic guanosine-adenosine synthase (cGAS. Using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus. TLR signaling was required for host defense, with its absence reducing interleukin (IL-1β production and neutrophil recruitment, resulting in increased bacterial growth. In contrast, absence of STING signaling had the opposite effect, enhancing the ability to restrict the infection. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered by S. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus.

  6. Depression as sickness behavior? A test of the host defense hypothesis in a high pathogen population.

    Science.gov (United States)

    Stieglitz, Jonathan; Trumble, Benjamin C; Thompson, Melissa Emery; Blackwell, Aaron D; Kaplan, Hillard; Gurven, Michael

    2015-10-01

    Sadness is an emotion universally recognized across cultures, suggesting it plays an important functional role in regulating human behavior. Numerous adaptive explanations of persistent sadness interfering with daily functioning (hereafter "depression") have been proposed, but most do not explain frequent bidirectional associations between depression and greater immune activation. Here we test several predictions of the host defense hypothesis, which posits that depression is part of a broader coordinated evolved response to infection or tissue injury (i.e. "sickness behavior") that promotes energy conservation and reallocation to facilitate immune activation. In a high pathogen population of lean and relatively egalitarian Bolivian forager-horticulturalists, we test whether depression and its symptoms are associated with greater baseline concentration of immune biomarkers reliably associated with depression in Western populations (i.e. tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1β], interleukin-6 [IL-6], and C-reactive protein [CRP]). We also test whether greater pro-inflammatory cytokine responses to ex vivo antigen stimulation are associated with depression and its symptoms, which is expected if depression facilitates immune activation. These predictions are largely supported in a sample of older adult Tsimane (mean±SD age=53.2±11.0, range=34-85, n=649) after adjusting for potential confounders. Emotional, cognitive and somatic symptoms of depression are each associated with greater immune activation, both at baseline and in response to ex vivo stimulation. The association between depression and greater immune activation is therefore not unique to Western populations. While our findings are not predicted by other adaptive hypotheses of depression, they are not incompatible with those hypotheses and future research is necessary to isolate and test competing predictions. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Systems engineering meets quantitative systems pharmacology: from low-level targets to engaging the host defenses.

    Science.gov (United States)

    Androulakis, Ioannis P

    2015-01-01

    Quantitative systems pharmacology aims at systematizing, in a model-based manner, the integration of systems biology and pharmacology in an effort to rationalize the process of assessing the ability of a drug to enhance well-being by off-setting the effects of a disease. Systems engineering, on the other hand, has enabled us to develop principles and methodologies for designing and operating engineered networks of structures exploring the integration of the underlying governing (design) laws. Although the computational tools which have resulted in major advances in the design, analysis, and operation of complex engineered structures have had tremendous success in the analysis of systems pharmacology models, it is argued in this opinion paper, that exploring the underlying conceptual foundation of complex systems engineering will enable us to move toward integrated models at the host level to explore, and possibly, induce synergies between low-level drug targets and higher level, systemic, defense mechanisms. This is an approach which would require refocusing of the key activities; however, it is likely the more promising approach as we enter the new era of personalized and precision medicine. We finally argue for the development of an allostatic approach to quantitative systems pharmacology and the development of an integrated framework for considering drugs in their broader context, beyond their local site of action. WIREs Syst Biol Med 2015, 7:101-112. doi: 10.1002/wsbm.1294 For further resources related to this article, please visit the WIREs website. The author has declared no conflicts of interest for this article. © 2015 Wiley Periodicals, Inc.

  8. Recent advances in host defense mechanisms/therapies against oral infectious diseases and consequences for systemic disease.

    Science.gov (United States)

    Gaffen, S L; Herzberg, M C; Taubman, M A; Van Dyke, T E

    2014-05-01

    The innate and adaptive immune systems are both crucial to oral disease mechanisms and their impact on systemic health status. Greater understanding of these interrelationships will yield opportunities to identify new therapeutic targets to modulate disease processes and/or increase host resistance to infectious or inflammatory insult. The topics addressed reflect the latest advances in our knowledge of the role of innate and adaptive immune systems and inflammatory mechanisms in infectious diseases affecting the oral cavity, including periodontitis and candidiasis. In addition, several potential links with systemic inflammatory conditions, such as cardiovascular disease, are explored. The findings elucidate some of the defense mechanisms utilized by host tissues, including the role of IL-17 in providing immunity to oral candidiasis, the antimicrobial defense of mucosal epithelial cells, and the pro-resolution effects of the natural inflammatory regulators, proresolvins and lipoxins. They also describe the role of immune cells in mediating pathologic bone resorption in periodontal disease. These insights highlight the potential for therapeutic benefit of immunomodulatory interventions that bolster or modulate host defense mechanisms in both oral and systemic disease. Among the promising new therapeutic approaches discussed here are epithelial cell gene therapy, passive immunization against immune cell targets, and the use of proresolvin agents.

  9. ELR chemokine signaling in host defense and disease in a viral model of central nervous system disease

    Directory of Open Access Journals (Sweden)

    Martin P Hosking

    2014-06-01

    Full Text Available Intracranial infection of the neurotropic JHM strain of mouse hepatitis virus (JHMV into the central nervous system (CNS of susceptible strains of mice results in an acute encephalomyelitis, accompanied by viral replication in glial cells and robust infiltration of virus-specific T cells that contribute to host defense through cytokine secretion and cytolytic activity. Mice that survive the acute stage of disease develop an immune-mediated demyelinating diseases characterized by viral persistence in white matter tracts and a chronic neuroinflammatory response dominated by T cells and macrophages. Early following JHMV infection, there is a dynamic expression of chemokines and chemokine receptors that contribute to neuroinflammation by regulating innate and adaptive immune responses as well influencing glial biology. In response to JHMV infection, we have shown that signaling through the chemokine receptor CXCR2 contributes to host defense through recruitment of polymorphonuclear cells (PMNs to the CNS that enhance permeability of the blood-brain-barrier (BBB and facilitating entry of virus-specific T cells into the parenchyma. Further, CXCR2 promotes the protection of oligodendroglia from cytokine-induced apoptosis and restricts the severity of demyelination. This review covers aspects related to the role of CXCR2 in host defense and disease in response to JHMV infection.

  10. An Insecticidal Compound Produced by an Insect-Pathogenic Bacterium Suppresses Host Defenses through Phenoloxidase Inhibition

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    Ihsan Ullah

    2014-12-01

    Full Text Available A bioassay-guided column chromatographic strategy was adopted in the present study to fractionate the culture extract of Photorhabdus temperata M1021 to identify potential insecticidal and antimicrobial compounds. An ethyl acetate (EtOAc culture extract of P. temperata was assayed against Galleria mellonella larvae through intra-hemocoel injection and exhibited 100% insect mortality within 60 h. The EtOAc fraction and an isolated compound exhibited phenoloxidase (PO inhibition of up to 60% and 63%, respectively. The compound was identified as 1,2-benzenedicarboxylic acid (phthalic acid, PA by gas chromatography-mass spectrometry and nuclear magnetic resonance. PA exhibited insecticidal activity against G. mellonella in a dose-dependent manner, and 100% insect mortality was observed at 108 h after injection of 1 M PA. In a PO inhibition assay, 0.5 and 1 M concentrations of PA were found to inhibit PO activity by 74% and 82%, respectively; and in a melanotic nodule formation assay, nodule formation was significantly inhibited (27 and 10 nodules by PA (0.5 and 1 M, respectively. PA was furthermore found to have substantial antioxidant activity and maximum antioxidant activity was 64.7% for 0.5 M PA as compare to control. Antibacterial activity was assessed by The MIC values ranged from 0.1 M to 0.5 M of PA. This study reports a multifunctional PA, a potential insecticidal agent, could a factor of insect mortality along with other toxins produced by P. temperata M1021.

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

    Science.gov (United States)

    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.

  12. Killing of trypanosomatid parasites by a modified bovine host defense peptide, BMAP-18.

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    Lee R Haines

    Full Text Available BACKGROUND: Tropical diseases caused by parasites continue to cause socioeconomic devastation that reverberates worldwide. There is a growing need for new control measures for many of these diseases due to increasing drug resistance exhibited by the parasites and problems with drug toxicity. One new approach is to apply host defense peptides (HDP; formerly called antimicrobial peptides to disease control, either to treat infected hosts, or to prevent disease transmission by interfering with parasites in their insect vectors. A potent anti-parasite effector is bovine myeloid antimicrobial peptide-27 (BMAP-27, a member of the cathelicidin family. Although BMAP-27 is a potent inhibitor of microbial growth, at higher concentrations it also exhibits cytotoxicity to mammalian cells. We tested the anti-parasite activity of BMAP-18, a truncated peptide that lacks the hydrophobic C-terminal sequence of the BMAP-27 parent molecule, an alteration that confers reduced toxicity to mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: BMAP-18 showed strong growth inhibitory activity against several species and life cycle stages of African trypanosomes, fish trypanosomes and Leishmania parasites in vitro. When compared to native BMAP-27, the truncated BMAP-18 peptide showed reduced cytotoxicity on a wide variety of mammalian and insect cells and on Sodalis glossindius, a bacterial symbiont of the tsetse vector. The fluorescent stain rhodamine 123 was used in immunofluorescence microscopy and flow cytometry experiments to show that BMAP-18 at low concentrations rapidly disrupted mitochondrial potential without obvious alteration of parasite plasma membranes, thus inducing death by apoptosis. Scanning electron microscopy revealed that higher concentrations of BMAP-18 induced membrane lesions in the parasites as early as 15 minutes after exposure, thus killing them by necrosis. In addition to direct killing of parasites, BMAP-18 was shown to inhibit LPS

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

    Science.gov (United States)

    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...

  14. Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Na; Zhu, Yongqun; Lu, Qiuhe; Hu, Liyan; Zheng, Yuqing; Shao, Feng (NIBS-China); (Zhejiang)

    2012-10-10

    Rab GTPases are frequent targets of vacuole-living bacterial pathogens for appropriate trafficking of the vacuole. Here we discover that bacterial effectors including VirA from nonvacuole Shigella flexneri and EspG from extracellular Enteropathogenic Escherichia coli (EPEC) harbor TBC-like dual-finger motifs and exhibits potent RabGAP activities. Specific inactivation of Rab1 by VirA/EspG disrupts ER-to-Golgi trafficking. S. flexneri intracellular persistence requires VirA TBC-like GAP activity that mediates bacterial escape from autophagy-mediated host defense. Rab1 inactivation by EspG severely blocks host secretory pathway, resulting in inhibited interleukin-8 secretion from infected cells. Crystal structures of VirA/EspG-Rab1-GDP-aluminum fluoride complexes highlight TBC-like catalytic role for the arginine and glutamine finger residues and reveal a 3D architecture distinct from that of the TBC domain. Structure of Arf6-EspG-Rab1 ternary complex illustrates a pathogenic signaling complex that rewires host Arf signaling to Rab1 inactivation. Structural distinctions of VirA/EspG further predict a possible extensive presence of TBC-like RabGAP effectors in counteracting various host defenses.

  15. Expression of immune-response genes in lepidopteran host is suppressed by venom from an endoparasitoid, Pteromalus puparum

    Directory of Open Access Journals (Sweden)

    Fang Qi

    2010-09-01

    Full Text Available Abstract Background The relationships between parasitoids and their insect hosts have attracted attention at two levels. First, the basic biology of host-parasitoid interactions is of fundamental interest. Second, parasitoids are widely used as biological control agents in sustainable agricultural programs. Females of the gregarious endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae inject venom along with eggs into their hosts. P. puparum does not inject polydnaviruses during oviposition. For this reason, P. puparum and its pupal host, the small white butterfly Pieris rapae (Lepidoptera: Pieridae, comprise an excellent model system for studying the influence of an endoparasitoid venom on the biology of the pupal host. P. puparum venom suppresses the immunity of its host, although the suppressive mechanisms are not fully understood. In this study, we tested our hypothesis that P. puparum venom influences host gene expression in the two main immunity-conferring tissues, hemocytes and fat body. Results At 1 h post-venom injection, we recorded significant decreases in transcript levels of 217 EST clones (revealing 113 genes identified in silico, including 62 unknown contigs derived from forward subtractive libraries of host hemocytes and in transcript levels of 288 EST clones (221 genes identified in silico, including 123 unknown contigs from libraries of host fat body. These genes are related to insect immune response, cytoskeleton, cell cycle and apoptosis, metabolism, transport, stress response and transcriptional and translational regulation. We verified the reliability of the suppression subtractive hybridization (SSH data with semi-quantitative RT-PCR analysis of a set of randomly selected genes. This analysis showed that most of the selected genes were down-regulated after venom injection. Conclusions Our findings support our hypothesis that P. puparum venom influences gene expression in host hemocytes and fat body. Specifically

  16. Which is more effective for suppressing an infectious disease: imperfect vaccination or defense against contagion?

    Science.gov (United States)

    Kuga, Kazuki; Tanimoto, Jun

    2018-02-01

    We consider two imperfect ways to protect against an infectious disease such as influenza, namely vaccination giving only partial immunity and a defense against contagion such as wearing a mask. We build up a new analytic framework considering those two cases instead of perfect vaccination, conventionally assumed as a premise, with the assumption of an infinite and well-mixed population. Our framework also considers three different strategy-updating rules based on evolutionary game theory: conventional pairwise comparison with one randomly selected agent, another concept of pairwise comparison referring to a social average, and direct alternative selection not depending on the usual copying concept. We successfully obtain a phase diagram in which vaccination coverage at equilibrium can be compared when assuming the model of either imperfect vaccination or a defense against contagion. The obtained phase diagram reveals that a defense against contagion is marginally inferior to an imperfect vaccination as long as the same coefficient value is used. Highlights - We build a new analytical framework for a vaccination game combined with the susceptible-infected-recovered (SIR) model. - Our model can evaluate imperfect provisions such as vaccination giving only partial immunity and a defense against contagion. - We obtain a phase diagram with which to compare the quantitative effects of partial vaccination and a defense against contagion.

  17. Lipooligosaccharide structure is an important determinant in the resistance of Neisseria gonorrhoeae to antimicrobial agents of innate host defense

    Directory of Open Access Journals (Sweden)

    Jacqueline T Balthazar

    2011-02-01

    Full Text Available The strict human pathogen Neisseria gonorrhoeae has caused the sexually transmitted infection termed gonorrhea for thousands of years. Over the millennia, the gonococcus has likely evolved mechanisms to evade host defense systems that operate on the genital mucosal surfaces in both males and females. Past research has shown that the presence or modification of certain cell envelope structures can significantly impact levels of gonococcal susceptibility to host-derived antimicrobial compounds that bathe genital mucosal surfaces and participate in innate host defense against invading pathogens. In order to facilitate the identification of gonococcal genes that are important in determining levels of bacterial susceptibility to mediators of innate host defense, we used the Himar I mariner in vitro mutagenesis system to construct a transposon insertion library in strain F62. As proof of principle that this strategy would be suitable for this purpose, we screened the library for mutants expressing decreased susceptibility to the bacteriolytic action of normal human serum (NHS. We found that a transposon insertion in the lgtD gene, which encodes an N-acetylgalactosamine transferase involved in the extension of the α-chain of lipooligosaccharide (LOS, could confer decreased susceptibility of strain F62 to complement-mediated killing by NHS. By complementation and chemical analyses, we demonstrated both linkage of the transposon insertion to the NHS-resistance phenotype and chemical changes in LOS structure that resulted from loss of LgtD production. Further truncation of the LOS α-chain or loss of phosphoethanolamine (PEA from the lipid A region of LOS also impacted levels of NHS-resistance. PEA decoration of lipid A also increased gonococcal resistance to the model cationic antimicrobial polymyxin B. Taken together, we conclude that the Himar I mariner in vitro mutagenesis procedure can facilitate studies on structures involved in gonococcal

  18. New Concepts in Immunity to Neisseria Gonorrhoeae: Innate Responses and Suppression of Adaptive Immunity Favor the Pathogen, Not the Host

    OpenAIRE

    Liu, Yingru; Feinen, Brandon; Russell, Michael W.

    2011-01-01

    It is well known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host’s immune defenses, we propose that it also has the ...

  19. Salivary proteins of spider mites suppress defenses in Nicotiana benthamiana and promote mite reproduction

    NARCIS (Netherlands)

    Villarroel, C.A.; Jonckheere, W.; Alba Cano, J.M.; Glas, J.J.; Dermauw, W.; Haring, M.A.; Van Leeuwen, T.; Schuurink, R.C.; Kant, M.R.

    2016-01-01

    Spider mites (Tetranychidae sp.) are widely occurring arthropod pests on cultivated plants. Feeding by the two-spotted spider mite T. urticae, a generalist herbivore, induces a defense response in plants that mainly depends on the phytohormones jasmonic acid and salicylic acid (SA). On tomato

  20. Auto-acetylation on K289 is not essential for HopZ1a-mediated plant defense suppression

    Directory of Open Access Journals (Sweden)

    Jose Sebastian Rufian

    2015-07-01

    Full Text Available The Pseudomonas syringae type III-secreted effector HopZ1a is a member of the HopZ / YopJ superfamily of effectors that triggers immunity in Arabidopsis. We have previously shown that HopZ1a suppresses both local (effector-triggered immunity, ETI and systemic immunity (systemic acquired resistance, SAR triggered by the heterologous effector AvrRpt2. HopZ1a has been shown to possess acetyltransferase activity, and this activity is essential to trigger immunity in Arabidopsis. HopZ1a acetyltransferase activity has been reported to require the auto-acetylation of the effector on a specific lysine (K289 residue. In this paper we analyze the relevance of autoacetylation of lysine residue 289 in HopZ1a ability to suppress plant defenses, and on the light of the results obtained, we also revise its relevance for HopZ1a avirulence activity. Our results indicate that, while the HopZ1aK289R mutant is impaired to some degree in its virulence and avirulence activities, is by no means phenotypically equivalent to the catalytically inactive HopZ1aC216A, since it is still able to trigger a defense response that induces detectable macroscopic HR and effectively protects Arabidopsis from infection, reducing growth of P. syringae within the plant. We also present evidence that the HopZ1aK289R mutant still displays virulence activities, partially suppressing both ETI and SAR.

  1. Auto-acetylation on K289 is not essential for HopZ1a-mediated plant defense suppression.

    Science.gov (United States)

    Rufián, José S; Lucía, Ainhoa; Macho, Alberto P; Orozco-Navarrete, Begoña; Arroyo-Mateos, Manuel; Bejarano, Eduardo R; Beuzón, Carmen R; Ruiz-Albert, Javier

    2015-01-01

    The Pseudomonas syringae type III-secreted effector HopZ1a is a member of the HopZ/YopJ superfamily of effectors that triggers immunity in Arabidopsis. We have previously shown that HopZ1a suppresses both local [effector-triggered immunity (ETI)] and systemic immunity [systemic acquired resistance (SAR)] triggered by the heterologous effector AvrRpt2. HopZ1a has been shown to possess acetyltransferase activity, and this activity is essential to trigger immunity in Arabidopsis. HopZ1a acetyltransferase activity has been reported to require the auto-acetylation of the effector on a specific lysine (K289) residue. In this paper we analyze the relevance of autoacetylation of lysine residue 289 in HopZ1a ability to suppress plant defenses, and on the light of the results obtained, we also revise its relevance for HopZ1a avirulence activity. Our results indicate that, while the HopZ1a(K289R) mutant is impaired to some degree in its virulence and avirulence activities, is by no means phenotypically equivalent to the catalytically inactive HopZ1a(C216A), since it is still able to trigger a defense response that induces detectable macroscopic HR and effectively protects Arabidopsis from infection, reducing growth of P. syringae within the plant. We also present evidence that the HopZ1a(K289R) mutant still displays virulence activities, partially suppressing both ETI and SAR.

  2. Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.

    Directory of Open Access Journals (Sweden)

    Nadine T Nehme

    2011-03-01

    Full Text Available 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.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.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.

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

    Directory of Open Access Journals (Sweden)

    Jeanne A Robert

    Full Text Available 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.

  4. Stealth proteins: in silico identification of a novel protein family rendering bacterial pathogens invisible to host immune defense.

    Directory of Open Access Journals (Sweden)

    Peter Sperisen

    2005-11-01

    Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

  5. Stealth Proteins: In Silico Identification of a Novel Protein Family Rendering Bacterial Pathogens Invisible to Host Immune Defense.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available There are a variety of bacterial defense strategies to survive in a hostile environment. Generation of extracellular polysaccharides has proved to be a simple but effective strategy against the host's innate immune system. A comparative genomics approach led us to identify a new protein family termed Stealth, most likely involved in the synthesis of extracellular polysaccharides. This protein family is characterized by a series of domains conserved across phylogeny from bacteria to eukaryotes. In bacteria, Stealth (previously characterized as SacB, XcbA, or WefC is encoded by subsets of strains mainly colonizing multicellular organisms, with evidence for a protective effect against the host innate immune defense. More specifically, integrating all the available information about Stealth proteins in bacteria, we propose that Stealth is a D-hexose-1-phosphoryl transferase involved in the synthesis of polysaccharides. In the animal kingdom, Stealth is strongly conserved across evolution from social amoebas to simple and complex multicellular organisms, such as Dictyostelium discoideum, hydra, and human. Based on the occurrence of Stealth in most Eukaryotes and a subset of Prokaryotes together with its potential role in extracellular polysaccharide synthesis, we propose that metazoan Stealth functions to regulate the innate immune system. Moreover, there is good reason to speculate that the acquisition and spread of Stealth could be responsible for future epidemic outbreaks of infectious diseases caused by a large variety of eubacterial pathogens. Our in silico identification of a homologous protein in the human host will help to elucidate the causes of Stealth-dependent virulence. At a more basic level, the characterization of the molecular and cellular function of Stealth proteins may shed light on fundamental mechanisms of innate immune defense against microbial invasion.

  6. Insecticidal activity of the metalloprotease AprA occurs through suppression of host cellular and humoral immunity.

    Science.gov (United States)

    Lee, Seung Ah; Jang, Seong Han; Kim, Byung Hyun; Shibata, Toshio; Yoo, Jinwook; Jung, Yunjin; Kawabata, Shun-Ichiro; Lee, Bok Luel

    2018-04-01

    The biochemical characterization of virulence factors from entomopathogenic bacteria is important to understand entomopathogen-insect molecular interactions. Pseudomonas entomophila is a typical entomopathogenic bacterium that harbors virulence factors against several insects. However, the molecular actions of these factors against host innate immune responses are not clearly elucidated. In this study, we observed that bean bugs (Riptortus pedestris) that were injected with P. entomophila were highly susceptible to this bacterium. To determine how P. entomophila counteracts the host innate immunity to survive within the insect, we purified a highly enriched protein with potential host insect-killing activity from the culture supernatant of P. entomophila. Then, a 45-kDa protein was purified to homogeneity and identified as AprA which is an alkaline zinc metalloprotease of the genus Pseudomonas by liquid chromatography mass spectrometry (LC-MS). Purified AprA showed a pronounced killing effect against host insects and suppressed both host cellular and humoral innate immunity. Furthermore, to show that AprA is an important insecticidal protein of P. entomophila, we used an aprA-deficient P. entomophila mutant strain (ΔaprA). When ΔaprA mutant cells were injected to host insects, this mutant exhibited extremely attenuated virulence. In addition, the cytotoxicity against host hemocytes and the antimicrobial peptide-degrading ability of the ΔaprA mutant were greatly decreased. These findings suggest that AprA functions as an important insecticidal protein of P. entomophila via suppression of host cellular and humoral innate immune responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Disease susceptibiliy in the zig-zag model of host-microbe Interactions: only a consequence of immune suppression?

    OpenAIRE

    Keller, Harald; Boyer, Laurent; Abad, Pierre

    2016-01-01

    For almost ten years, the Zig-Zag model has provided a convenient framework for explaining the molecular bases of compatibility and incompatibility in plant-microbe interactions (Jones and Dangl, 2006). According to the Zig-Zag model, disease susceptibility is a consequence of the suppression of host immunity during the evolutionary arms race between plants and pathogens. The Zig-Zag model thus fits well with biotrophic interactions, but is less applicable to interactions involving pathogens ...

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

    Science.gov (United States)

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

    2008-01-01

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

  9. Adaptive Immunity-Dependent Intestinal Hypermotility Contributes to Host Defense against Giardia spp.

    OpenAIRE

    Andersen, Yolanda S.; Gillin, Frances D.; Eckmann, Lars

    2006-01-01

    Humans infected with Giardia exhibit intestinal hypermotility, but the underlying mechanisms and functional significance are uncertain. Here we show in murine models of giardiasis that small-intestinal hypermotility occurs in a delayed fashion relative to peak parasite burden, is dependent on adaptive immune defenses, and contributes to giardial clearance.

  10. Attachment, penetration and early host defense mechanisms during the infection of filamentous brown algae by Eurychasma dicksonii.

    Science.gov (United States)

    Tsirigoti, Amerssa; Beakes, Gordon W; Hervé, Cécile; Gachon, Claire M M; Katsaros, Christos

    2015-05-01

    Eurychasma dicksonii is one of the most common and widespread marine pathogens and attacks a broad spectrum of more than 45 brown algal species. The present study focuses on the mechanism used by the pathogen to attach on the host cell wall and force its way into algal cells. Ultrastructural examination revealed a needle-like structure which develops within the attached spore and extends along its main axis. Particular cell wall modifications are present at the basal part of the spore (adhesorium pad) and guide the needle-like tool to penetrate perpendicularly the host cell wall. The unique injection mechanism is shared with Haptoglossa species which suggests that this is an important characteristic of early diverging oomycetes. Furthermore, the encystment and adhesion mechanism of E. dicksonii shows significant similarities with other oomycetes, some of which are plant pathogens. Staining and immunolabelling techniques showed the deposition of β-1,3-glucans on the host cell wall at the pathogen penetration site, a strategy similar to physical responses previously described only in infected plant cells. It is assumed that the host defense in terms of callose-like deposition is an ancient response to infection.

  11. Haematophagous arthropod saliva and host defense system: a tale of tear and blood

    Directory of Open Access Journals (Sweden)

    Andrade Bruno B.

    2005-01-01

    Full Text Available The saliva from blood-feeding arthropod vectors is enriched with molecules that display diverse functions that mediate a successful blood meal. They function not only as weapons against host's haemostatic, inflammatory and immune responses but also as important tools to pathogen establishment. Parasites, virus and bacteria taking advantage of vectors' armament have adapted to facilitate their entry in the host. Today, many salivary molecules have been identified and characterized as new targets to the development of future vaccines. Here we focus on current information on vector's saliva and the molecules responsible to modify host's hemostasis and immune response, also regarding their role in disease transmission.

  12. OsRDR6 plays role in host defense against double-stranded RNA virus, Rice Dwarf Phytoreovirus.

    Science.gov (United States)

    Hong, Wei; Qian, Dan; Sun, Runhong; Jiang, Lin; Wang, Yu; Wei, Chunhong; Zhang, Zhongkai; Li, Yi

    2015-07-13

    RNAi is a major antiviral defense response in plant and animal model systems. RNA-dependent RNA polymerase 6 (RDR6) is an essential component of RNAi, which plays an important role in the resistance against viruses in the model plants. We found previously that rice RDR6 (OsRDR6) functioned in the defense against Rice stripe virus (RSV), and Rice Dwarf Phytoreovirus (RDV) infection resulted in down-regulation of expression of RDR6. Here we report our new findings on the function of OsRDR6 against RDV. Our result showed that down-regulation of OsRDR6 through the antisense (OsRDR6AS) strategy increased rice susceptibility to RDV infection while over-expression of OsRDR6 had no effect on RDV infection. The accumulation of RDV vsiRNAs was reduced in the OsRDR6AS plants. In the OsRDR6 over-expressed plants, the levels of OsRDR6 RNA transcript and protein were much higher than that in the control plants. Interestingly, the accumulation level of OsRDR6 protein became undetectable after RDV infection. This finding indicated that the translation and/or stability of OsRDR6 protein were negatively impacted upon RDV infection. This new finding provides a new light on the function of RDR6 in plant defense response and the cross-talking between factors encoded by host plant and double-stranded RNA viruses.

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

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    Martina Kalle

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

  14. Functional genomics identifies type I interferon pathway as central for host defense against Candida albicans

    NARCIS (Netherlands)

    Smeekens, Sanne P.; Ng, Aylwin; Kumar, Vinod; Johnson, Melissa D.; Plantinga, Theo S.; van Diemen, Cleo; Arts, Peer; Verwiel, Eugene T. P.; Gresnigt, Mark S.; Fransen, Karin; van Sommeren, Suzanne; Oosting, Marije; Cheng, Shih-Chin; Joosten, Leo A. B.; Hoischen, Alexander; Kullberg, Bart-Jan; Scott, William K.; Perfect, John R.; van der Meer, Jos W. M.; Wijmenga, Cisca; Netea, Mihai G.; Xavier, Ramnik J.

    Candida albicans is the most common human fungal pathogen causing mucosal and systemic infections. However, human antifungal immunity remains poorly defined. Here by integrating transcriptional analysis and functional genomics, we identified Candida-specific host defence mechanisms in humans.

  15. LPS inmobilization on porous and non-porous supports as an approach for the isolation of anti-LPS host-defense peptides.

    Directory of Open Access Journals (Sweden)

    Carlos eLopez-Abarrategui

    2013-12-01

    Full Text Available Lipopolysaccharides (LPS are the major molecular component of the outer membrane of Gram-negative bacteria. This molecule is recognized as a sign of bacterial infection, responsible for the development of local inflammatory response and, in extreme cases, septic shock. Unfortunately, despite substantial advances in the pathophysiology of sepsis, there is no efficacious therapy against this syndrome yet. As a consequence, septic shock syndrome continues to increase, reaching mortality rates over 50% in some cases. Even though many preclinical studies and clinical trials have been conducted, there is no FDA-approved drug yet that interacts directly against LPS. Cationic host defense peptides could be an alternative solution since they possess both antimicrobial and antiseptic properties. Host defense peptides are small, positively charged peptides which are evolutionarily conserved components of the innate immune response. In fact, binding to diverse chemotypes of LPS and inhibition of LPS-induced pro-inflammatory cytokines from macrophages have been demonstrated for different host defense peptides (HDPs. Curiously, none of them have been isolated by their affinity to LPS. A diversity of supports could be useful for such biological interaction and suitable for isolating host defense peptides that recognize LPS. This approach could expand the rational search for anti-LPS host defense peptides.

  16. Methyl jasmonate regulates antioxidant defense and suppresses arsenic uptake in Brassica napus L.

    Directory of Open Access Journals (Sweden)

    Muhammad A Farooq

    2016-04-01

    Full Text Available Methyl jasmonate (MJ is an important plant growth regulator, involved in plant defense against abiotic stresses, however its possible function in response to metal stress is poorly understood. In the present study, the effect of MJ on physiological and biochemical changes of the plants exposed to arsenic (As stress were investigated in two Brassica napus L. cultivars (ZS 758 – a black seed type, and Zheda 622 – a yellow seed type. The As treatment at 200 µM was more phytotoxic, however its combined application with MJ resulted in significant increase in leaf chlorophyll fluorescence, biomass production and reduced malondialdehyde content compared with As stressed plants. The application of MJ minimized the oxidative stress, as revealed via a lower level of reactive oxygen species (ROS synthesis (H2O2 and OH- in leaves and the maintenance of high redox states of glutathione and ascorbate. Enhanced enzymatic activities and gene expression of important antioxidants (SOD, APX, CAT, POD, secondary metabolites (PAL, PPO, CAD and induction of lypoxygenase gene suggest that MJ plays an effective role in the regulation of multiple transcriptional pathways which were involved in oxidative stress responses. The content of As was higher in yellow seeded plants (cv. Zheda 622 as compared to black seeded plants (ZS 758. The application of MJ significantly reduced the As content in leaves and roots of both cultivars. Findings of the present study reveal that MJ improves ROS scavenging through enhanced antioxidant defense system, secondary metabolite and reduced As contents in both the cultivars.

  17. Ticks and tick-borne pathogens at the cutaneous interface: host defenses, tick countermeasures, and a suitable environment for pathogen establishment

    Directory of Open Access Journals (Sweden)

    Stephen eWikel

    2013-11-01

    Full Text Available Ticks are unique among hematophagous arthropods by continuous attachment to host skin and blood feeding for days; complexity and diversity of biologically active molecules differentially expressed in saliva of tick species; their ability to modulate the host defenses of pain and itch, hemostasis, inflammation, innate and adaptive immunity, and wound healing; and, the diverse array of infectious agents they transmit. All of these interactions occur at the cutaneous interface in a complex sequence of carefully choreographed host defense responses and tick countermeasures resulting in an environment that facilitates successful blood feeding and establishment of tick-borne infectious agents within the host. Here, we examine diverse patterns of tick attachment to host skin, blood feeding mechanisms, salivary gland transcriptomes, bioactive molecules in tick saliva, timing of pathogen transmission, and host responses to tick bite. Ticks engage and modulate cutaneous and systemic immune defenses involving keratinocytes, natural killer cells, dendritic cells, T cell subpopulations (Th1, Th2, Th17, Treg , B cells, neutrophils, mast cells, basophils, endothelial cells, cytokines, chemokines, complement, and extracellular matrix. A framework is proposed that integrates tick induced changes of skin immune effectors with their ability to respond to tick-borne pathogens. Implications of these changes are addressed. What are the consequences of tick modulation of host cutaneous defenses? Does diversity of salivary gland transcriptomes determine differential modulation of host inflammation and immune defenses and therefore, in part, the clades of pathogens effectively transmitted by different tick species? Do ticks create an immunologically modified cutaneous environment that enhances specific pathogen establishment? Can tick saliva molecules be used to develop vaccines that block pathogen transmission?

  18. Increased host investment in extrafloral nectar (EFN) improves the efficiency of a mutualistic defensive service.

    Science.gov (United States)

    González-Teuber, Marcia; Silva Bueno, Juan Carlos; Heil, Martin; Boland, Wilhelm

    2012-01-01

    Extrafloral nectar (EFN) plays an important role as plant indirect defence through the attraction of defending ants. Like all rewards produced in the context of a mutualism, however, EFN is in danger of being exploited by non-ant consumers that do not defend the plant against herbivores. Here we asked whether plants, by investing more in EFN, can improve their indirect defence, or rather increase the risk of losing this investment to EFN thieves. We used the obligate plant-ant Acacia-Pseudomyrmex system and examined experimentally in the field during the dry and the rainy seasons how variations in EFN secretion are related to (i) ant activity, to (ii) the ant-mediated defence against herbivores and (iii) the exploitation of EFN by non-ant consumers. Extrafloral investment enhanced ant recruitment and was positively related to the ant mediated defence against herbivores. The ant-mediated protection from exploiters also increased in proportion to the nectar sugar concentration. Although the daily peak of EFN production coincided with the highest activity of EFN thieves, Pseudomyrmex ferrugineus ants protected this resource effectively from exploiters. Nevertheless, the defensive effects by ants differed among seasons. During the dry season, plants grew slower and secreted more EFN than in the rainy season, and thus, experienced a higher level of ant-mediated indirect defence. Our results show that an increased plant investment in an indirect defence trait can improve the resulting defensive service against both herbivores and exploiters. EFN secretion by obligate ant-plants represents a defensive trait for which the level of investment correlates positively with the beneficial effects obtained.

  19. CXC chemokine receptor 2 contributes to host defense in murine urinary tract infection

    NARCIS (Netherlands)

    Olszyna, D. P.; Florquin, S.; Sewnath, M.; Branger, J.; Speelman, P.; van Deventer, S. J.; Strieter, R. M.; van der Poll, T.

    2001-01-01

    CXC chemokines have been implicated in the recruitment of neutrophils to sites of infection. To determine the role of CXC chemokines in the host response to urinary tract infection (UTI), female mice were treated with an antibody against the major CXC chemokine receptor in the mouse, CXCR2, before

  20. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice

    NARCIS (Netherlands)

    de Stoppelaar, Sacha F.; van 't Veer, Cornelis; Claushuis, Theodora A. M.; Albersen, Bregje J. A.; Roelofs, Joris J. T. H.; van der Poll, Tom

    2014-01-01

    Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median

  1. Neutrophil extracellular traps in the host defense against sepsis induced by Burkholderia pseudomallei (melioidosis)

    NARCIS (Netherlands)

    de Jong, Hanna K.; Koh, Gavin C. K. W.; Achouiti, Ahmed; van der Meer, Anne J.; Bulder, Ingrid; Stephan, Femke; Roelofs, Joris J. T. H.; Day, Nick P. J.; Peacock, Sharon J.; Zeerleder, Sacha; Wiersinga, W. Joost

    2014-01-01

    Neutrophil extracellular traps (NETs) are a central player in the host response to bacteria: neutrophils release extracellular DNA (nucleosomes) and neutrophil elastase to entrap and kill bacteria. We studied the role of NETs in Burkholderia pseudomallei infection (melioidosis), an important cause

  2. A novel Meloidogyne enterolobii effector MeTCTP promotes parasitism by suppressing programmed cell death in host plants.

    Science.gov (United States)

    Zhuo, Kan; Chen, Jiansong; Lin, Borong; Wang, Jing; Sun, Fengxia; Hu, Lili; Liao, Jinling

    2017-01-01

    Meloidogyne enterolobii is one of the most important plant-parasitic nematodes that can overcome the Mi-1 resistance gene and damage many economically important crops. Translationally controlled tumour protein (TCTP) is a multifunctional protein that exists in various eukaryotes and plays an important role in parasitism. In this study, a novel M. enterolobii TCTP effector, named MeTCTP, was identified and functionally characterized. MeTCTP was specifically expressed within the dorsal gland and was up-regulated during M. enterolobii parasitism. Transient expression of MeTCTP in protoplasts from tomato roots showed that MeTCTP was localized in the cytoplasm of the host cells. Transgenic Arabidopsis thaliana plants overexpressing MeTCTP were more susceptible to M. enterolobii infection than wild-type plants in a dose-dependent manner. By contrast, in planta RNA interference (RNAi) targeting MeTCTP suppressed the expression of MeTCTP in infecting nematodes and attenuated their parasitism. Furthermore, MeTCTP could suppress programmed cell death triggered by the pro-apoptotic protein BAX. These results demonstrate that MeTCTP is a novel plant-parasitic nematode effector that promotes parasitism, probably by suppressing programmed cell death in host plants. © 2016 BSPP and John Wiley & Sons Ltd.

  3. Evidence of a salt refuge: chytrid infection loads are suppressed in hosts exposed to salt.

    Science.gov (United States)

    Stockwell, M P; Clulow, J; Mahony, M J

    2015-03-01

    With the incidence of emerging infectious diseases on the rise, it is becoming increasingly important to identify refuge areas that protect hosts from pathogens and therefore prevent population declines. For the chytrid fungus Batrachochytrium dendrobatidis, temperature and humidity refuge areas for amphibian hosts exist but are difficult to manipulate. Other environmental features that may affect the outcome of infection include water quality, drying regimes, abundance of alternate hosts and isolation from other hosts. We identified relationships between water bodies with these features and infection levels in the free-living hosts inhabiting them. Where significant relationships were identified, we used a series of controlled experiments to test for causation. Infection loads were negatively correlated with the salt concentration of the aquatic habitat and the degree of water level fluctuation and positively correlated with fish abundance. However, only the relationship with salt was confirmed experimentally. Free-living hosts inhabiting water bodies with mean salinities of up to 3.5 ppt had lower infection loads than those exposed to less salt. The experiment confirmed that exposure to sodium chloride concentrations >2 ppt significantly reduced host infection loads compared to no exposure (0 ppt). These results suggest that the exposure of amphibians to salt concentrations found naturally in lentic habitats may be responsible for the persistence of some susceptible species in the presence of B. dendrobatidis. By manipulating the salinity of water bodies, it may be possible to create refuges for declining amphibians, thus allowing them to be reintroduced to their former ranges.

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

    DEFF Research Database (Denmark)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath

    2012-01-01

    Gram-negative sepsis is accompanied by a disproportionate innate immune response and excessive coagulation mainly induced by endotoxins released from bacteria. Due to rising antibiotic resistance and current lack of other effective treatments there is an urgent need for new therapies. We here...... present a new treatment concept for sepsis and endotoxin-mediated shock, based on host defense peptides from the C-terminal part of human thrombin, found to have a broad and inhibitory effect on multiple sepsis pathologies. Thus, the peptides abrogate pro-inflammatory cytokine responses to endotoxin...... sepsis, the peptide GKY25, while mediating a modest antimicrobial effect, significantly inhibited the pro-inflammatory response, decreased fibrin deposition and leakage in the lungs, as well as reduced mortality. Taken together, the capacity of such thrombin-derived peptides to simultaneously modulate...

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

    Science.gov (United States)

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

    2012-01-01

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

  6. Seven-up facilitates insect counter-defense by suppressing cathepsin B expression.

    Science.gov (United States)

    Ahn, Ji-Eun; Guarino, Linda A; Zhu-Salzman, Keyan

    2007-06-01

    When challenged by the dietary soybean cysteine protease inhibitor scN, the cowpea bruchid (Callosobruchus maculatus) adapts to the inhibitory effects by readjusting the transcriptome of its digestive system, including the specific activation of a cathepsin B-like cysteine protease CmCatB. To understand the transcriptional regulation of CmCatB, we cloned a portion of its promoter and demonstrated its activity in Drosophila cells using a chloramphenicol acetyltransferase reporter system. EMSAs detected differential DNA-binding activity between nuclear extracts of scN-adapted and -unadapted midguts. Two tandem chicken ovalbumin upstream promoter (COUP) elements were identified in the CmCatB promoter that specifically interacted with a protein factor unique to nuclear extracts of unadapted insect guts, where CmCatB expression was repressed. Seven-up (Svp) is a COUP-TF-related transcription factor that interacted with the COUP responsive element. Polyclonal anti-(mosquito Svp) serum abolished the specific DNA-binding activity in cowpea bruchid midgut extracts, suggesting that the protein factor is an Svp homolog. Subsequent cloning of a cowpea bruchid Svp (CmSvp) indicated that it shares a high degree of amino acid sequence similarity with COUP-TF/Svp orphan nuclear receptor family members from varied species. The protein was more abundant in scN-unadapted insect guts than scN-adapted guts, consistent with the observed DNA-binding activity. Furthermore, CmCatB expression was repressed when CmSvp was transiently expressed in Drosophila cells, most likely through COUP binding. These findings indicate that CmSvp may contribute to insect counter-defense, in part by inhibiting CmCatB expression under normal growth conditions, but releasing the inhibition when insects are challenged by dietary protease inhibitors.

  7. Suppression of cotton leaf curl disease symptoms in Gossypium hirsutum through over expression of host-encoded miRNAs.

    Science.gov (United States)

    Akmal, Mohd; Baig, Mirza S; Khan, Jawaid A

    2017-12-10

    in any of the healthy looking transgenic lines. In this study for the first time, efficacy of the host (G. arboreum)-encoded miRNAs against CLCuD symptoms was experimentally demonstrated through overexpression of miR398 and miR2950 in G. hirsutum var. HS6 plants. Computational prediction of miRNAs targeting virus genome and their subsequent implication in translational inhibition or cleavage based suppression of viral mRNA via overexpression could help in generating virus resistant plants. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Ironing Out the Wrinkles in Host Defense: Interactions between Iron Homeostasis and Innate Immunity

    Science.gov (United States)

    Wang, Lijian; Cherayil, Bobby J.

    2009-01-01

    Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Recent advances in our understanding of the molecular regulation of iron metabolism have shed new light on how alterations in iron homeostasis both contribute to and influence innate immunity. In this article, we review what is currently known about the role of iron in the response to infection. PMID:20375603

  9. Ubiquitin systems mark pathogen-containing vacuoles as targets for host defense by guanylate binding proteins.

    Science.gov (United States)

    Haldar, Arun K; Foltz, Clémence; Finethy, Ryan; Piro, Anthony S; Feeley, Eric M; Pilla-Moffett, Danielle M; Komatsu, Masaki; Frickel, Eva-Maria; Coers, Jörn

    2015-10-13

    Many microbes create and maintain pathogen-containing vacuoles (PVs) as an intracellular niche permissive for microbial growth and survival. The destruction of PVs by IFNγ-inducible guanylate binding protein (GBP) and immunity-related GTPase (IRG) host proteins is central to a successful immune response directed against numerous PV-resident pathogens. However, the mechanism by which IRGs and GBPs cooperatively detect and destroy PVs is unclear. We find that host cell priming with IFNγ prompts IRG-dependent association of Toxoplasma- and Chlamydia-containing vacuoles with ubiquitin through regulated translocation of the E3 ubiquitin ligase tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6). This initial ubiquitin labeling elicits p62-mediated escort and deposition of GBPs to PVs, thereby conferring cell-autonomous immunity. Hypervirulent strains of Toxoplasma gondii evade this process via specific rhoptry protein kinases that inhibit IRG function, resulting in blockage of downstream PV ubiquitination and GBP delivery. Our results define a ubiquitin-centered mechanism by which host cells deliver GBPs to PVs and explain how hypervirulent parasites evade GBP-mediated immunity.

  10. Serratia marcescens suppresses host cellular immunity via the production of an adhesion-inhibitory factor against immunosurveillance cells.

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-02-28

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis.

  11. Serratia marcescens Suppresses Host Cellular Immunity via the Production of an Adhesion-inhibitory Factor against Immunosurveillance Cells*

    Science.gov (United States)

    Ishii, Kenichi; Adachi, Tatsuo; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-01-01

    Injection of a culture supernatant of Serratia marcescens into the bloodstream of the silkworm Bombyx mori increased the number of freely circulating immunosurveillance cells (hemocytes). Using a bioassay with live silkworms, serralysin metalloprotease was purified from the culture supernatant and identified as the factor responsible for this activity. Serralysin inhibited the in vitro attachment of both silkworm hemocytes and murine peritoneal macrophages. Incubation of silkworm hemocytes or murine macrophages with serralysin resulted in degradation of the cellular immune factor BmSPH-1 or calreticulin, respectively. Furthermore, serralysin suppressed in vitro phagocytosis of bacteria by hemocytes and in vivo bacterial clearance in silkworms. Disruption of the ser gene in S. marcescens attenuated its host killing ability in silkworms and mice. These findings suggest that serralysin metalloprotease secreted by S. marcescens suppresses cellular immunity by decreasing the adhesive properties of immunosurveillance cells, thereby contributing to bacterial pathogenesis. PMID:24398686

  12. Interferon-γ Is a Crucial Activator of Early Host Immune Defense against Mycobacterium ulcerans Infection in Mice.

    Science.gov (United States)

    Bieri, Raphael; Bolz, Miriam; Ruf, Marie-Thérèse; Pluschke, Gerd

    2016-02-01

    Buruli ulcer (BU), caused by infection with Mycobacterium ulcerans, is a chronic necrotizing human skin disease associated with the production of the cytotoxic macrolide exotoxin mycolactone. Despite extensive research, the type of immune responses elicited against this pathogen and the effector functions conferring protection against BU are not yet fully understood. While histopathological analyses of advanced BU lesions have demonstrated a mainly extracellular localization of the toxin producing acid fast bacilli, there is growing evidence for an early intra-macrophage growth phase of M. ulcerans. This has led us to investigate whether interferon-γ might play an important role in containing M. ulcerans infections. In an experimental Buruli ulcer mouse model we found that interferon-γ is indeed a critical regulator of early host immune defense against M. ulcerans infections. Interferon-γ knockout mice displayed a faster progression of the infection compared to wild-type mice. This accelerated progression was reflected in faster and more extensive tissue necrosis and oedema formation, as well as in a significantly higher bacterial burden after five weeks of infection, indicating that mice lacking interferon-γ have a reduced capacity to kill intracellular bacilli during the early intra-macrophage growth phase of M. ulcerans. This data demonstrates a prominent role of interferon-γ in early defense against M. ulcerans infection and supports the view that concepts for vaccine development against tuberculosis may also be valid for BU.

  13. Pseudomonas fluorescens induces strain-dependent and strain-independent host plant responses in defense networks, primary metabolism and photosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Pelletier, Dale A [ORNL; Morrell-Falvey, Jennifer L [ORNL; Karve, Abhijit A [ORNL; Lu, Tse-Yuan S [ORNL; Tschaplinski, Timothy J [ORNL; Tuskan, Gerald A [ORNL; Chen, Jay [ORNL; Martin, Madhavi Z [ORNL; Jawdy, Sara [ORNL; Weston, David [ORNL; Doktycz, Mitchel John [ORNL; Schadt, Christopher Warren [ORNL

    2012-01-01

    Colonization of plants by nonpathogenic Pseudomonas fluorescens strains can confer enhanced defense capacity against a broad spectrum of pathogens. Few studies, however, have linked defense pathway regulation to primary metabolism and physiology. In this study, physiological data, metabolites, and transcript profiles are integrated to elucidate how molecular networks initiated at the root-microbe interface influence shoot metabolism and whole-plant performance. Experiments with Arabidopsis thaliana were performed using the newly identified P. fluorescens GM30 or P. fluorescens Pf-5 strains. Co-expression networks indicated that Pf-5 and GM30 induced a subnetwork specific to roots enriched for genes participating in RNA regulation, protein degradation, and hormonal metabolism. In contrast, only GM30 induced a subnetwork enriched for calcium signaling, sugar and nutrient signaling, and auxin metabolism, suggesting strain dependence in network architecture. In addition, one subnetwork present in shoots was enriched for genes in secondary metabolism, photosynthetic light reactions, and hormone metabolism. Metabolite analysis indicated that this network initiated changes in carbohydrate and amino acid metabolism. Consistent with this, we observed strain-specific responses in tryptophan and phenylalanine abundance. Both strains reduced host plant carbon gain and fitness, yet provided a clear fitness benefit when plants were challenged with the pathogen P. syringae DC3000.

  14. Host Defense and the Airway Epithelium: Frontline Responses That Protect against Bacterial Invasion and Pneumonia

    Directory of Open Access Journals (Sweden)

    Nicholas A. Eisele

    2011-01-01

    Full Text Available Airway epithelial cells are the first line of defense against invading microbes, and they protect themselves through the production of carbohydrate and protein matrices concentrated with antimicrobial products. In addition, they act as sentinels, expressing pattern recognition receptors that become activated upon sensing bacterial products and stimulate downstream recruitment and activation of immune cells which clear invading microbes. Bacterial pathogens that successfully colonize the lungs must resist these mechanisms or inhibit their production, penetrate the epithelial barrier, and be prepared to resist a barrage of inflammation. Despite the enormous task at hand, relatively few virulence factors coordinate the battle with the epithelium while simultaneously providing resistance to inflammatory cells and causing injury to the lung. Here we review mechanisms whereby airway epithelial cells recognize pathogens and activate a program of antibacterial pathways to prevent colonization of the lung, along with a few examples of how bacteria disrupt these responses to cause pneumonia.

  15. Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD 2 in Host Defense during Pneumococcal Pneumonia.

    Directory of Open Access Journals (Sweden)

    Tijmen J Hommes

    Full Text Available Streptococcus (S. pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/- and wild-type (Wt alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39, an isogenic capsule locus deletion mutant (D39Δcps or serotype 3 S. pneumoniae (6303 via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.

  16. Stimulation of host immune defenses by a small molecule protects C. elegans from bacterial infection.

    Science.gov (United States)

    Pukkila-Worley, Read; Feinbaum, Rhonda; Kirienko, Natalia V; Larkins-Ford, Jonah; Conery, Annie L; Ausubel, Frederick M

    2012-01-01

    The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (∼1.3% of all genes) in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans-based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens.

  17. Stimulation of host immune defenses by a small molecule protects C. elegans from bacterial infection.

    Directory of Open Access Journals (Sweden)

    Read Pukkila-Worley

    Full Text Available The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (∼1.3% of all genes in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans-based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens.

  18. Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication

    Science.gov (United States)

    Huang, Hanxia; Falgout, Barry; Takeda, Kazuyo; Yamada, Kenneth M.; Dhawan, Subhash

    2017-01-01

    We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited hemin-induced HO-1 expression with major reductions of > 90% in ZIKV replication, with little toxicity to infected cells. Silencing expression of HO-1 or its upstream regulatory gene, nuclear factor erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV infection, suggesting an important role for induction of these intracellular mediators in retarding ZIKV replication. The inverse correlation between hemin-induced HO-1 levels and ZIKV replication provides a potentially useful therapeutic modality based on stimulation of an innate cellular response against Zika virus infection. PMID:28068513

  19. Influenza A Virus Protein PA-X Contributes to Viral Growth and Suppression of the Host Antiviral and Immune Responses.

    Science.gov (United States)

    Hayashi, Tsuyoshi; MacDonald, Leslie A; Takimoto, Toru

    2015-06-01

    Influenza virus infection causes global inhibition of host protein synthesis in infected cells. This host shutoff is thought to allow viruses to escape from the host antiviral response, which restricts virus replication and spread. Although the mechanism of host shutoff is unclear, a novel viral protein expressed by ribosomal frameshifting, PA-X, was found to play a major role in influenza virus-induced host shutoff. However, little is known about the impact of PA-X expression on currently circulating influenza A virus pathogenicity and the host antiviral response. In this study, we rescued a recombinant influenza A virus, A/California/04/09 (H1N1, Cal), containing mutations at the frameshift motif in the polymerase PA gene (Cal PA-XFS). Cal PA-XFS expressed significantly less PA-X than Cal wild type (WT). Cal WT, but not Cal PA-XFS, induced degradation of host β-actin mRNA and suppressed host protein synthesis, supporting the idea that PA-X induces host shutoff via mRNA decay. Moreover, Cal WT inhibited beta interferon (IFN-β) expression and replicated more rapidly than Cal PA-XFS in human respiratory cells. Mice infected with Cal PA-XFS had significantly lower levels of viral growth and greater expression of IFN-β mRNA in their lungs than mice infected with Cal WT. Importantly, more antihemagglutinin and neutralizing antibodies were produced in Cal PA-XFS-infected mice than in Cal WT-infected mice, despite the lower level of virus replication in the lungs. Our data indicate that PA-X of the pandemic H1N1 virus has a strong impact on viral growth and the host innate and acquired immune responses to influenza virus. Virus-induced host protein shutoff is considered to be a major factor allowing viruses to evade innate and acquired immune recognition. We provide evidence that the 2009 H1N1 influenza A virus protein PA-X plays a role in virus replication and inhibition of host antiviral response by means of its host protein synthesis shutoff activity both in vitro

  20. DMPD: Toll-like receptors and the host defense against microbial pathogens: bringingspecificity to the innate-immune system. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available gingspecificity to the innate-immune system. Netea MG, van der Graaf C, Van der Meer JW, Kullberg BJ. J Leuk... the host defense against microbial pathogens: bringingspecificity to the innate-immune system... bringingspecificity to the innate-immune system. Authors Netea MG, van der Graaf C, Van der Meer JW, Kullbe

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Carlos H Z Martins

    Full Text Available 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.

  3. ISG15 in Host Defense Against Candida albicans Infection in a Mouse Model of Fungal Keratitis.

    Science.gov (United States)

    Dong, Chen; Gao, Nan; Ross, Bing X; Yu, Fu-Shin X

    2017-06-01

    ISG15, a di-ubiquitin-like protein, is critical for controlling certain viral and bacterial infections. We sought to determine if ISG15 plays a role in corneal innate immunity against Candida albicans (C. albicans) using a C57BL/6 (B6) mouse model of human fungal keratitis. Scarified corneas of adult B6 mice were pretreated with TLR5 ligand flagellin and then inoculated with C. albicans. The expression of ISG15 and other genes involved in ISG15 conjugation (ISGylation) was determined by real-time PCR. ISG15 expression and distribution in infected corneas were assessed by immunohistochemistry. ISGylation was examined by Western blotting. siRNA knockdown and recombinant ISG15 were used to elucidate the effects of ISG15 on controlling fungal keratitis by clinical scoring, fungal number plate counting, ELISA cytokine determination, and polymorphonuclear leukocytes (PMN) infiltration measurement. Heat-killed C. albicans induced expression of ISG15, and hBD2 was markedly enhanced by flagellin-pretreatment in cultured human primary corneal epithelial cells (CECs). In vivo, C. albicans infection induced the expression of ISG15, ISGylation-associated genes (UBE1L, UBCH8, and HERC5), and ISGylation in mouse CECs, all of which were enhanced by flagellin-pretreatment. siRNA knockdown of ISG15 increased keratitis severity, dampened flagellin-induced protection, and greatly suppressed the expressions of ISGylation enzymes, IFN-γ, but not CXCL2 in B6 mouse CECs. Recombinant ISG15, on the other hand, enhanced corneal innate immunity against C. albicans and suppressed infection-induced IL-1β, but not IL-Ra expression. ISG15 alone induced the expression of IL-1Ra, CXCL10, and CRAMP in mouse CECs. ISG15 was upregulated and secreted in cultured human CECs in response to challenge in a type 1 IFN-dependent manner. Our data, for the first time, demonstrate that ISG15 acts as an immunomodulator in the cornea and plays a critical role in controlling fungal keratitis.

  4. NLRP12 negatively regulates proinflammatory cytokine production and host defense against Brucella abortus.

    Science.gov (United States)

    Silveira, Tatiana N; Gomes, Marco Túlio R; Oliveira, Luciana S; Campos, Priscila C; Machado, Gabriela G; Oliveira, Sergio C

    2017-01-01

    Brucella abortus is the causative agent of brucellosis, which causes abortion in domestic animals and undulant fever in humans. This bacterium infects and proliferates mainly in macrophages and dendritic cells, where it is recognized by pattern recognition receptors (PRRs) including Nod-like receptors (NLRs). Our group recently demonstrated the role of AIM2 and NLRP3 in Brucella recognition. Here, we investigated the participation of NLRP12 in innate immune response to B. abortus. We show that NLRP12 inhibits the early production of IL-12 by bone marrow-derived macrophages upon B. abortus infection. We also observed that NLRP12 suppresses in vitro NF-κB and MAPK signaling in response to Brucella. Moreover, we show that NLRP12 modulates caspase-1 activation and IL-1β secretion in B. abortus infected-macrophages. Furthermore, we show that mice lacking NLRP12 are more resistant in the early stages of B. abortus infection: NLRP12 -/- infected-mice have reduced bacterial burdens in the spleens and increased production of IFN-γ and IL-1β compared with wild-type controls. In addition, NLRP12 deficiency leads to reduction in granuloma number and size in mouse livers. Altogether, our findings suggest that NLRP12 plays an important role in negatively regulating the early inflammatory responses against B. abortus. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Alcohol Consumption Modulates Host Defense in Rhesus Macaques by Altering Gene Expression in Circulating Leukocytes.

    Science.gov (United States)

    Barr, Tasha; Girke, Thomas; Sureshchandra, Suhas; Nguyen, Christina; Grant, Kathleen; Messaoudi, Ilhem

    2016-01-01

    Several lines of evidence indicate that chronic alcohol use disorder leads to increased susceptibility to several viral and bacterial infections, whereas moderate alcohol consumption decreases the incidence of colds and improves immune responses to some pathogens. In line with these observations, we recently showed that heavy ethanol intake (average blood ethanol concentrations > 80 mg/dl) suppressed, whereas moderate alcohol consumption (blood ethanol concentrations consumption. To uncover the molecular basis for impaired immunity with heavy alcohol consumption and enhanced immune response with moderate alcohol consumption, we performed a transcriptome analysis using PBMCs isolated on day 7 post-modified vaccinia Ankara vaccination, the earliest time point at which we detected differences in T cell and Ab responses. Overall, chronic heavy alcohol consumption reduced the expression of immune genes involved in response to infection and wound healing and increased the expression of genes associated with the development of lung inflammatory disease and cancer. In contrast, chronic moderate alcohol consumption upregulated the expression of genes involved in immune response and reduced the expression of genes involved in cancer. To uncover mechanisms underlying the alterations in PBMC transcriptomes, we profiled the expression of microRNAs within the same samples. Chronic heavy ethanol consumption altered the levels of several microRNAs involved in cancer and immunity and known to regulate the expression of mRNAs differentially expressed in our data set. Copyright © 2015 by The American Association of Immunologists, Inc.

  6. ABA Suppresses Botrytis cinerea Elicited NO Production in Tomato to Influence H2O2 Generation and Increase Host Susceptibility.

    Science.gov (United States)

    Sivakumaran, Anushen; Akinyemi, Aderemi; Mandon, Julian; Cristescu, Simona M; Hall, Michael A; Harren, Frans J M; Mur, Luis A J

    2016-01-01

    Abscisic acid (ABA) production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with nitric oxide (NO) in tomato following challenge with the ABA-synthesizing pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production - an established mediator of defense against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME) suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS) generation but this was reduced in both L-NAME and ABA-treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production.

  7. ABA Suppresses Botrytis cinerea Elicited NO Production in Tomato to Influence H2O2 Generation and Increase Host Susceptibility

    Science.gov (United States)

    Sivakumaran, Anushen; Akinyemi, Aderemi; Mandon, Julian; Cristescu, Simona M.; Hall, Michael A.; Harren, Frans J. M.; Mur, Luis A. J.

    2016-01-01

    Abscisic acid (ABA) production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with nitric oxide (NO) in tomato following challenge with the ABA-synthesizing pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production – an established mediator of defense against this pathogen – occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME) suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS) generation but this was reduced in both L-NAME and ABA-treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production. PMID:27252724

  8. Host heterogeneous ribonucleoprotein K (hnRNP K as a potential target to suppress hepatitis B virus replication.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available BACKGROUND: Hepatitis B virus (HBV infection results in complications such as cirrhosis and hepatocellular carcinoma. Suppressing viral replication in chronic HBV carriers is an effective approach to controlling disease progression. Although antiviral compounds are available, we aimed to identify host factors that have a significant effect on viral replication efficiency. METHODS AND FINDINGS: We studied a group of hepatitis B carriers by associating serum viral load with their respective HBV genomes, and observed a significant association between high patient serum viral load with a natural sequence variant within the HBV enhancer II (Enh II regulatory region at position 1752. Using a viral fragment as an affinity binding probe, we isolated a host DNA-binding protein belonging to the class of heterogeneous nuclear ribonucleoproteins--hnRNP K--that binds to and modulates the replicative efficiency of HBV. In cell transfection studies, overexpression of hnRNP K augmented HBV replication, while gene silencing of endogenous hnRNP K carried out by small interfering RNAs resulted in a significant reduction of HBV viral load. CONCLUSION: The evidence presented in this study describes a wider role for hnRNP K beyond maintenance of host cellular functions and may represent a novel target for pharmacologic intervention of HBV replication.

  9. Disease interactions in a shared host plant: effects of pre-existing viral infection on cucurbit plant defense responses and resistance to bacterial wilt disease.

    Directory of Open Access Journals (Sweden)

    Lori R Shapiro

    Full Text Available Both biotic and abiotic stressors can elicit broad-spectrum plant resistance against subsequent pathogen challenges. However, we currently have little understanding of how such effects influence broader aspects of disease ecology and epidemiology in natural environments where plants interact with multiple antagonists simultaneously. In previous work, we have shown that healthy wild gourd plants (Cucurbita pepo ssp. texana contract a fatal bacterial wilt infection (caused by Erwinia tracheiphila at significantly higher rates than plants infected with Zucchini yellow mosaic virus (ZYMV. We recently reported evidence that this pattern is explained, at least in part, by reduced visitation of ZYMV-infected plants by the cucumber beetle vectors of E. tracheiphila. Here we examine whether ZYMV-infection may also directly elicit plant resistance to subsequent E. tracheiphila infection. In laboratory studies, we assayed the induction of key phytohormones (SA and JA in single and mixed infections of these pathogens, as well as in response to the feeding of A. vittatum cucumber beetles on healthy and infected plants. We also tracked the incidence and progression of wilt disease symptoms in plants with prior ZYMV infections. Our results indicate that ZYMV-infection slightly delays the progression of wilt symptoms, but does not significantly reduce E. tracheiphila infection success. This observation supports the hypothesis that reduced rates of wilt disease in ZYMV-infected plants reflect reduced visitation by beetle vectors. We also documented consistently strong SA responses to ZYMV infection, but limited responses to E. tracheiphila in the absence of ZYMV, suggesting that the latter pathogen may effectively evade or suppress plant defenses, although we observed no evidence of antagonistic cross-talk between SA and JA signaling pathways. We did, however, document effects of E. tracheiphila on induced responses to herbivory that may influence host

  10. Disease Interactions in a Shared Host Plant: Effects of Pre-Existing Viral Infection on Cucurbit Plant Defense Responses and Resistance to Bacterial Wilt Disease

    Science.gov (United States)

    Mauck, Kerry E.; Pulido, Hannier; De Moraes, Consuelo M.; Stephenson, Andrew G.; Mescher, Mark C.

    2013-01-01

    Both biotic and abiotic stressors can elicit broad-spectrum plant resistance against subsequent pathogen challenges. However, we currently have little understanding of how such effects influence broader aspects of disease ecology and epidemiology in natural environments where plants interact with multiple antagonists simultaneously. In previous work, we have shown that healthy wild gourd plants (Cucurbita pepo ssp. texana) contract a fatal bacterial wilt infection (caused by Erwinia tracheiphila) at significantly higher rates than plants infected with Zucchini yellow mosaic virus (ZYMV). We recently reported evidence that this pattern is explained, at least in part, by reduced visitation of ZYMV-infected plants by the cucumber beetle vectors of E. tracheiphila. Here we examine whether ZYMV-infection may also directly elicit plant resistance to subsequent E. tracheiphila infection. In laboratory studies, we assayed the induction of key phytohormones (SA and JA) in single and mixed infections of these pathogens, as well as in response to the feeding of A. vittatum cucumber beetles on healthy and infected plants. We also tracked the incidence and progression of wilt disease symptoms in plants with prior ZYMV infections. Our results indicate that ZYMV-infection slightly delays the progression of wilt symptoms, but does not significantly reduce E. tracheiphila infection success. This observation supports the hypothesis that reduced rates of wilt disease in ZYMV-infected plants reflect reduced visitation by beetle vectors. We also documented consistently strong SA responses to ZYMV infection, but limited responses to E. tracheiphila in the absence of ZYMV, suggesting that the latter pathogen may effectively evade or suppress plant defenses, although we observed no evidence of antagonistic cross-talk between SA and JA signaling pathways. We did, however, document effects of E. tracheiphila on induced responses to herbivory that may influence host-plant quality for (and

  11. IRAK-M regulation and function in host defense and immune homeostasis

    Directory of Open Access Journals (Sweden)

    Leah L.N. Hubbard

    2010-06-01

    Full Text Available Antigen presenting cells (APCs of the innate immune system sense a wide range of pathogens via pattern recognition receptors (PRRs. Engagement of certain PRRs can induce production of pro-inflammatory mediators that facilitate effective clearance of pathogen. Toll-like receptors (TLRs are a well described group of PRRs that belong to the TLR/Interleukin-1 receptor (IL-1R superfamily. However, TLR/IL-1R induction of pro-inflammatory mediators must be regulated to prevent excessive inflammation and tissue damage. One molecule of recent interest that is known to inhibit TLR/IL-1R signaling is interleukin-1 receptor associated kinase (IRAK-M, also known as IRAK-3. IRAK-M is expressed in a number of immune and epithelial cells types, and through its inhibition of pro-inflammatory cytokine production, IRAK-M can regulate immune homeostasis and tolerance in a number of infectious and non-infectious diseases. Furthermore, use of IRAK-M deficient animals has increased our understanding of the importance of IRAK-M in regulating immune responsiveness to a variety of pathogens. Although IRAK-M expression is typically induced through TLR signaling, IRAK-M can also be expressed in response to various endogenous and exogenous soluble factors as well as cell surface and intracellular signaling molecules. This review will focus on clinical scenarios in which expression of IRAK-M is beneficial (as in early sepsis and those situations where IRAK-M expression is harmful to the host (as in cancer and following bone marrow transplant. There is strong rationale for therapeutic targeting of IRAK-M for clinical benefit. However, effective targeting will require a greater understanding of the transcriptional regulation of this gene.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

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

  14. Platelet and endothelial cell P-selectin are required for host defense against Klebsiella pneumoniae-induced pneumosepsis.

    Science.gov (United States)

    de Stoppelaar, S F; Van't Veer, C; Roelofs, J J T H; Claushuis, T A M; de Boer, O J; Tanck, M W T; Hoogendijk, A J; van der Poll, T

    2015-06-01

    Sepsis is associated with activation of platelets and endothelial cells accompanied by enhanced P-selectin surface expression. Both platelet- and endothelial P-selectin have been associated with leukocyte recruitment and induction of inflammatory alterations. Klebsiella (K.) pneumoniae is a common human sepsis pathogen, particularly in the context of pneumonia. Wild-type (WT) and P-selectin-deficient (Selp(-/-) ) mice or bone marrow chimeric mice were infected with K. pneumoniae via the airways to induce pneumosepsis. Mice were sacrificed during early (12 h after infection) or late-stage (44 h) sepsis for analyses, or followed in a survival study. Selp(-/-) mice displayed 10-1000-fold higher bacterial burdens in the lungs, blood and distant organs during late-stage sepsis. P-selectin deficiency did not influence leukocyte recruitment to the lungs, but was associated with decreased platelet-monocyte complexes and increased cytokine release. Bone marrow transfer studies revealed a role for both platelet and endothelial cell P-selectin as mice deficient in platelet or endothelial cell P-selectin displayed an intermediate phenotype in bacterial loads and survival compared with full wild-type or full knockout control mice. Both platelet and endothelial cell P-selectin contribute to host defense during Klebsiella pneumosepsis. © 2015 International Society on Thrombosis and Haemostasis.

  15. Atg7 deficiency impairs host defense against Klebsiella pneumoniae by impacting bacterial clearance, survival and inflammatory responses in mice.

    Science.gov (United States)

    Ye, Yan; Li, Xuefeng; Wang, Wenxue; Ouedraogo, Kiswendsida Claude; Li, Yi; Gan, Changpei; Tan, Shirui; Zhou, Xikun; Wu, Min

    2014-09-01

    Klebsiella pneumoniae (Kp) is a Gram-negative bacterium that can cause serious infections in humans. Autophagy-related gene 7 (Atg7) has been implicated in certain bacterial infections; however, the role of Atg7 in macrophage-mediated immunity against Kp infection has not been elucidated. Here we showed that Atg7 expression was significantly increased in murine alveolar macrophages (MH-S) upon Kp infection, indicating that Atg7 participated in host defense. Knocking down Atg7 with small-interfering RNA increased bacterial burdens in MH-S cells. Using cell biology assays and whole animal imaging analysis, we found that compared with wild-type mice atg7 knockout (KO) mice exhibited increased susceptibility to Kp infection, with decreased survival rates, decreased bacterial clearance, and intensified lung injury. Moreover, Kp infection induced excessive proinflammatory cytokines and superoxide in the lung of atg7 KO mice. Similarly, silencing Atg7 in MH-S cells markedly increased expression levels of proinflammatory cytokines. Collectively, these findings reveal that Atg7 offers critical resistance to Kp infection by modulating both systemic and local production of proinflammatory cytokines. Copyright © 2014 the American Physiological Society.

  16. Suppression of host immune response by the core protein of hepatitis C virus: possible implications for hepatitis C virus persistence.

    Science.gov (United States)

    Large, M K; Kittlesen, D J; Hahn, Y S

    1999-01-15

    Hepatitis C virus (HCV) is a major human pathogen causing mild to severe liver disease worldwide. This positive strand RNA virus is remarkably efficient at establishing chronic infections. Although a high rate of genetic variability may facilitate viral escape and persistence in the face of Ag-specific immune responses, HCV may also encode proteins that facilitate evasion of immunological surveillance. To address the latter possibility, we examined the influence of specific HCV gene products on the host immune response to vaccinia virus in a murine model. Various vaccinia/HCV recombinants expressing different regions of the HCV polyprotein were used for i.p. inoculation of BALB/c mice. Surprisingly, a recombinant expressing the N-terminal half of the polyprotein (including the structural proteins, p7, NS2, and a portion of NS3; vHCV-S) led to a dose-dependent increase in mortality. Increased mortality was not observed for a recombinant expressing the majority of the nonstructural region or for a negative control virus expressing the beta-galactosidase protein. Examination of T cell responses in these mice revealed a marked suppression of vaccinia-specific CTL responses and a depressed production of IFN-gamma and IL-2. By using a series of vaccinia/HCV recombinants, we found that the HCV core protein was sufficient for immunosuppression, prolonged viremia, and increased mortality. These results suggest that the HCV core protein plays an important role in the establishment and maintenance of HCV infection by suppressing host immune responses, in particular the generation of virus-specific CTLs.

  17. Hidden suppression of sex ratio distortion suggests Red queen dynamics between Wolbachia and its dwarf spider host.

    Science.gov (United States)

    Vanthournout, B; Hendrickx, F

    2016-08-01

    Genetic conflict theory predicts strong selection for host nuclear factors suppressing endosymbiont effects on reproduction; however, evidence of these suppressors is currently scarce. This can either be caused by a low suppressor evolution rate, or if suppressors originate frequently, by rapid spread and concurrent masking of their activity by silencing the endosymbiont effect. To explore this, we use two populations of a dwarf spider with a similar female bias, caused by a Wolbachia infection. Using inter- and intrapopulation crosses, we determine that one of these populations demonstrates a higher suppressing capability towards Wolbachia despite having a similar population sex ratio. This suggests that spider and endosymbiont are locked in so-called red queen dynamics where, despite continuous coevolution, average fitness remains the same, hence hiding the presence of the suppressor. Finding different suppressor activity in populations that even lack phenotypic differentiation (i.e. similar sex ratio) further supports the hypothesis that suppressors originate often, but are often hidden by their own mode of action by countering endosymbiont effects. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  18. Quantitative and qualitative stem rust resistance factors in barley are associated with transcriptional suppression of defense regulons.

    Science.gov (United States)

    Moscou, Matthew J; Lauter, Nick; Steffenson, Brian; Wise, Roger P

    2011-07-01

    Stem rust (Puccinia graminis f. sp. tritici; Pgt) is a devastating fungal disease of wheat and barley. Pgt race TTKSK (isolate Ug99) is a serious threat to these Triticeae grain crops because resistance is rare. In barley, the complex Rpg-TTKSK locus on chromosome 5H is presently the only known source of qualitative resistance to this aggressive Pgt race. Segregation for resistance observed on seedlings of the Q21861 × SM89010 (QSM) doubled-haploid (DH) population was found to be predominantly qualitative, with little of the remaining variance explained by loci other than Rpg-TTKSK. In contrast, analysis of adult QSM DH plants infected by field inoculum of Pgt race TTKSK in Njoro, Kenya, revealed several additional quantitative trait loci that contribute to resistance. To molecularly characterize these loci, Barley1 GeneChips were used to measure the expression of 22,792 genes in the QSM population after inoculation with Pgt race TTKSK or mock-inoculation. Comparison of expression Quantitative Trait Loci (eQTL) between treatments revealed an inoculation-dependent expression polymorphism implicating Actin depolymerizing factor3 (within the Rpg-TTKSK locus) as a candidate susceptibility gene. In parallel, we identified a chromosome 2H trans-eQTL hotspot that co-segregates with an enhancer of Rpg-TTKSK-mediated, adult plant resistance discovered through the Njoro field trials. Our genome-wide eQTL studies demonstrate that transcript accumulation of 25% of barley genes is altered following challenge by Pgt race TTKSK, but that few of these genes are regulated by the qualitative Rpg-TTKSK on chromosome 5H. It is instead the chromosome 2H trans-eQTL hotspot that orchestrates the largest inoculation-specific responses, where enhanced resistance is associated with transcriptional suppression of hundreds of genes scattered throughout the genome. Hence, the present study associates the early suppression of genes expressed in this host-pathogen interaction with enhancement

  19. Quantitative and qualitative stem rust resistance factors in barley are associated with transcriptional suppression of defense regulons.

    Directory of Open Access Journals (Sweden)

    Matthew J Moscou

    2011-07-01

    Full Text Available Stem rust (Puccinia graminis f. sp. tritici; Pgt is a devastating fungal disease of wheat and barley. Pgt race TTKSK (isolate Ug99 is a serious threat to these Triticeae grain crops because resistance is rare. In barley, the complex Rpg-TTKSK locus on chromosome 5H is presently the only known source of qualitative resistance to this aggressive Pgt race. Segregation for resistance observed on seedlings of the Q21861 × SM89010 (QSM doubled-haploid (DH population was found to be predominantly qualitative, with little of the remaining variance explained by loci other than Rpg-TTKSK. In contrast, analysis of adult QSM DH plants infected by field inoculum of Pgt race TTKSK in Njoro, Kenya, revealed several additional quantitative trait loci that contribute to resistance. To molecularly characterize these loci, Barley1 GeneChips were used to measure the expression of 22,792 genes in the QSM population after inoculation with Pgt race TTKSK or mock-inoculation. Comparison of expression Quantitative Trait Loci (eQTL between treatments revealed an inoculation-dependent expression polymorphism implicating Actin depolymerizing factor3 (within the Rpg-TTKSK locus as a candidate susceptibility gene. In parallel, we identified a chromosome 2H trans-eQTL hotspot that co-segregates with an enhancer of Rpg-TTKSK-mediated, adult plant resistance discovered through the Njoro field trials. Our genome-wide eQTL studies demonstrate that transcript accumulation of 25% of barley genes is altered following challenge by Pgt race TTKSK, but that few of these genes are regulated by the qualitative Rpg-TTKSK on chromosome 5H. It is instead the chromosome 2H trans-eQTL hotspot that orchestrates the largest inoculation-specific responses, where enhanced resistance is associated with transcriptional suppression of hundreds of genes scattered throughout the genome. Hence, the present study associates the early suppression of genes expressed in this host-pathogen interaction with

  20. Host-pathogen interactions between the human innate immune system and Candida albicans—understanding and modeling defense and evasion strategies

    Science.gov (United States)

    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

  1. Host suppression and bioinformatics for sequence-based characterization of unknown pathogens.

    Energy Technology Data Exchange (ETDEWEB)

    Branda, Steven S.; Lane, Todd W.; Misra, Milind; Meagher, Robert J.; Patel, Kamlesh D.; Kaiser, Julia N.

    2009-11-01

    Bioweapons and emerging infectious diseases pose formidable and growing threats to our national security. Rapid advances in biotechnology and the increasing efficiency of global transportation networks virtually guarantee that the United States will face potentially devastating infectious disease outbreaks caused by novel ('unknown') pathogens either intentionally or accidentally introduced into the population. Unfortunately, our nation's biodefense and public health infrastructure is primarily designed to handle previously characterized ('known') pathogens. While modern DNA assays can identify known pathogens quickly, identifying unknown pathogens currently depends upon slow, classical microbiological methods of isolation and culture that can take weeks to produce actionable information. In many scenarios that delay would be costly, in terms of casualties and economic damage; indeed, it can mean the difference between a manageable public health incident and a full-blown epidemic. To close this gap in our nation's biodefense capability, we will develop, validate, and optimize a system to extract nucleic acids from unknown pathogens present in clinical samples drawn from infected patients. This system will extract nucleic acids from a clinical sample, amplify pathogen and specific host response nucleic acid sequences. These sequences will then be suitable for ultra-high-throughput sequencing (UHTS) carried out by a third party. The data generated from UHTS will then be processed through a new data assimilation and Bioinformatic analysis pipeline that will allow us to characterize an unknown pathogen in hours to days instead of weeks to months. Our methods will require no a priori knowledge of the pathogen, and no isolation or culturing; therefore it will circumvent many of the major roadblocks confronting a clinical microbiologist or virologist when presented with an unknown or engineered pathogen.

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

    Science.gov (United States)

    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.

  3. Induction of porcine host defense peptide gene expression by short-chain fatty acids and their analogs.

    Directory of Open Access Journals (Sweden)

    Xiangfang Zeng

    Full Text Available Dietary modulation of the synthesis of endogenous host defense peptides (HDPs represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections. However, HDP regulation by dietary compounds such as butyrate is species-dependent. To examine whether butyrate could induce HDP expression in pigs, we evaluated the expressions of a panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages, and primary monocytes in response to sodium butyrate treatment by real-time PCR. We revealed that butyrate is a potent inducer of multiple, but not all, HDP genes. Porcine β-defensin 2 (pBD2, pBD3, epididymis protein 2 splicing variant C (pEP2C, and protegrins were induced markedly in response to butyrate, whereas pBD1 expression remained largely unaltered in any cell type. Additionally, a comparison of the HDP-inducing efficacy among saturated free fatty acids of different aliphatic chain lengths revealed that fatty acids containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2 cells, with butyrate being the most potent and long-chain fatty acids having only a marginal effect. We further investigated a panel of butyrate analogs for their efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4-phenylbutyrate to be comparable with butyrate. Identification of butyrate and several analogs with a strong capacity to induce HDP gene expression in pigs provides attractive candidates for further evaluation of their potential as novel alternatives to antibiotics in augmenting innate immunity and disease resistance of pigs.

  4. Looped host defense peptide CLP-19 binds to microtubules and inhibits surface expression of TLR4 on mouse macrophages.

    Science.gov (United States)

    Li, Di; Liu, Yao; Yang, Ya; Chen, Jian-hong; Yang, Jie; Zou, Lin-yun; Tian, Zhi-qiang; Lv, Jun; Xia, Pei-yuan

    2013-06-15

    The looped host defense peptide CLP-19 is derived from a highly functional core region of the Limulus anti-LPS factor and exerts robust anti-LPS activity by directly interacting with LPS in the extracellular space. We previously showed that prophylactic administration of CLP-19 even 20 h prior to LPS challenge might significantly increase the survival rate in a lethal endotoxin shock mouse model. Such an effect may be associated with immune regulation of CLP-19. To investigate the underlying mechanisms, peptide affinity chromatography, immunofluorescence, and Western blotting procedures were used to identify α- and β-tubulin as direct and specific binding partners of CLP-19 in the mouse macrophage cell line RAW 264.7. Bioinformatic analysis using the AutoDock Vina molecular docking and PyMOL molecular graphics system predicted that CLP-19 would bind to the functional residues of both α- and β-tubulin and would be located within the groove of microtubules. Tubulin polymerization assay revealed that CLP-19 might induce polymerization of microtubules and prevent depolymerization. The immunoregulatory effect of CLP-19 involving microtubules was investigated by flow cytometry, immunofluorescence, and Western blotting, which showed that CLP-19 prophylactic treatment of RAW 264.7 cells significantly inhibited LPS-induced surface expression of TLR4. Taken together, these results suggest that CLP-19 binding to microtubules disrupts the dynamic equilibrium of microtubules, reducing the efficacy of microtubule-dependent vesicular transport that would otherwise translocate TLR4 from the endoplasmic reticulum to the cell surface.

  5. Involvement of Host Defense Mechanisms against Toxoplasma gondii Infection in Anhedonic and Despair-Like Behaviors in Mice.

    Science.gov (United States)

    Mahmoud, Motamed Elsayed; Fereig, Ragab; Nishikawa, Yoshifumi

    2017-04-01

    Toxoplasma gondii is a pathogen relevant to psychiatric disorders. We recently showed that reactivation of chronic T. gondii infection induced depression-like behaviors in mice. Furthermore, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2,3-dioxygenase (IDO), inflammation, and interferon gamma (IFN-γ) to anhedonic and despair-related behaviors in T. gondii -infected mice by using sucrose preference and forced-swim tests, respectively. First, we confirmed that BALB/c mice exhibited both sickness and depression-like behaviors during acute infection. Treatment of infected wild-type mice with minocycline (anti-inflammatory drug) abated sickness and anhedonic and despair-like behaviors, whereas in T. gondii -infected mice, treatment normalized kynurenine/tryptophan (Kyn/Trp) ratios in both plasma and brain tissue. Additionally, T. gondii infection failed to induce anhedonic and despair-like behaviors or increase the Kyn/Trp ratio in immunocompromised (IFN-γ -/- ) mice, whereas sickness behavior was observed in both immunocompetent and IFN-γ -/- mice following infection. Furthermore, treatment with 1-methyl tryptophan (an IDO inhibitor) did not affect locomotor activity, attenuated clinical scores and anhedonic and despair-like behaviors, and resulted in normal Kyn/Trp ratios in T. gondii -infected wild-type mice. Although low levels of serotonin and dopamine were observed in the brain during acute and chronic infections, anhedonic and despair-like behaviors were not detected in the chronic stage of infection. Collectively, our results demonstrated that immune enhancement in response to infection with T. gondii resulted in IFN-γ production, IDO activation, and inflammation associated with anhedonic and despair-like behaviors. Copyright © 2017 American

  6. Identification of Host Defense-Related Proteins Using Label-Free Quantitative Proteomic Analysis of Milk Whey from Cows with Staphylococcus aureus Subclinical Mastitis

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    Shaimaa Abdelmegid

    2017-12-01

    Full Text Available Staphylococcus aureus is the most common contagious pathogen associated with bovine subclinical mastitis. Current diagnosis of S. aureus mastitis is based on bacteriological culture of milk samples and somatic cell counts, which lack either sensitivity or specificity. Identification of milk proteins that contribute to host defense and their variable responses to pathogenic stimuli would enable the characterization of putative biomarkers of subclinical mastitis. To accomplish this, milk whey samples from healthy and mastitic dairy cows were analyzed using a label-free quantitative proteomics approach. In total, 90 proteins were identified, of which 25 showed significant differential abundance between healthy and mastitic samples. In silico functional analyses indicated the involvement of the differentially abundant proteins in biological mechanisms and signaling pathways related to host defense including pathogen-recognition, direct antimicrobial function, and the acute-phase response. This proteomics and bioinformatics analysis not only facilitates the identification of putative biomarkers of S. aureus subclinical mastitis but also recapitulates previous findings demonstrating the abundance of host defense proteins in intramammary infection. All mass spectrometry data are available via ProteomeXchange with identifier PXD007516.

  7. Dual role of Fcγ receptors in host defense and disease in Borrelia burgdorferi-infected mice

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    Alexia Anne Belperron

    2014-06-01

    Full Text Available Arthritis in mice infected with the Lyme disease spirochete, Borrelia burgdorferi, results from the influx of innate immune cells responding to the pathogen in the joint and is influenced in part by mouse genetics. Production of inflammatory cytokines by innate immune cells in vitro is largely mediated by Toll-like receptor (TLR interaction with Borrelia lipoproteins, yet surprisingly mice deficient in TLR2 or the TLR signaling molecule MyD88 still develop arthritis comparable to that seen in wild type mice after B. burgdorferi infection. These findings suggest that other, MyD88-independent inflammatory pathways can contribute to arthritis expression. Clearance of B. burgdorferi is dependent on the production of specific antibody and phagocytosis of the organism. As Fc receptors (FcγR are important for IgG-mediated clearance of immune complexes and opsonized particles by phagocytes, we examined the role that FcγR play in host defense and disease in B. burgdorferi-infected mice. B. burgdorferi-infected mice deficient in the Fc receptor common gamma chain (FcεRγ-/- mice harbored ~10 fold more spirochetes than similarly infected wild type mice, and this was associated with a transient increase in arthritis severity. While the elevated pathogen burdens seen in B. burgdorferi-infected MyD88-/- mice were not affected by concomitant deficiency in FcγR, arthritis was reduced in FcεRγ-/-MyD88-/- mice in comparison to wild type or single knockout mice. Gene expression analysis from infected joints demonstrated that absence of both MyD88 and FcγR lowers mRNA levels of proteins involved in inflammation, including Cxcl1 (KC, Xcr1 (Gpr5, IL-1beta, and C reactive protein. Taken together, our results demonstrate a role for FcγR-mediated immunity in limiting pathogen burden and arthritis in mice during the acute phase of B. burgdorferi infection, and further suggest that this pathway contributes to the arthritis that develops in B. burgdorferi

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

    Science.gov (United States)

    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.

  9. Mutations in fetal genes involved in innate immunity and host defense against microbes increase risk of preterm premature rupture of membranes (PPROM).

    Science.gov (United States)

    Modi, Bhavi P; Teves, Maria E; Pearson, Laurel N; Parikh, Hardik I; Haymond-Thornburg, Hannah; Tucker, John L; Chaemsaithong, Piya; Gomez-Lopez, Nardhy; York, Timothy P; Romero, Roberto; Strauss, Jerome F

    2017-11-01

    Twin studies have revealed a significant contribution of the fetal genome to risk of preterm birth. Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm delivery. Infection and inflammation of the fetal membranes is commonly found associated with PPROM. We carried out whole exome sequencing (WES) of genomic DNA from neonates born of African-American mothers whose pregnancies were complicated by PPROM (76) or were normal term pregnancies (N = 43) to identify mutations in 35 candidate genes involved in innate immunity and host defenses against microbes. Targeted genotyping of mutations in the candidates discovered by WES was conducted on an additional 188 PPROM cases and 175 controls. We identified rare heterozygous nonsense and frameshift mutations in several of the candidate genes, including CARD6, CARD8, DEFB1, FUT2, MBL2, NLP10, NLRP12, and NOD2. We discovered that some mutations (CARD6, DEFB1, FUT2, MBL2, NLRP10, NOD2) were present only in PPROM cases. We conclude that rare damaging mutations in innate immunity and host defense genes, the majority being heterozygous, are more frequent in neonates born of pregnancies complicated by PPROM. These findings suggest that the risk of preterm birth in African-Americans may be conferred by mutations in multiple genes encoding proteins involved in dampening the innate immune response or protecting the host against microbial infection and microbial products. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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.

  11. Smuggling across the border: how arthropod-borne pathogens evade and exploit the host defense system of the skin.

    Science.gov (United States)

    Bernard, Quentin; Jaulhac, Benoit; Boulanger, Nathalie

    2014-05-01

    The skin is a critical barrier between hosts and pathogens in arthropod-borne diseases. It harbors many resident cells and specific immune cells to arrest or limit infections by secreting inflammatory molecules or by directly killing pathogens. However, some pathogens are able to use specific skin cells and arthropod saliva for their initial development, to hide from the host immune system, and to establish persistent infection in the vertebrate host. A better understanding of the initial mechanisms taking place in the skin should allow the development of new strategies to fight these vector-borne pathogens that are spread worldwide and are of major medical importance.

  12. Abscisic Acid Promotes Susceptibility to the Rice Leaf Blight Pathogen Xanthomonas oryzae pv oryzae by Suppressing Salicylic Acid-Mediated Defenses.

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    Jing Xu

    Full Text Available The plant hormone abscisic acid (ABA is involved in a wide variety of plant processes, including the initiation of stress-adaptive responses to various environmental cues. Recently, ABA also emerged as a central factor in the regulation and integration of plant immune responses, although little is known about the underlying mechanisms. Aiming to advance our understanding of ABA-modulated disease resistance, we have analyzed the impact, dynamics and interrelationship of ABA and the classic defense hormone salicylic acid (SA during progression of rice infection by the leaf blight pathogen Xanthomonas oryzae pv. oryzae (Xoo. Consistent with ABA negatively regulating resistance to Xoo, we found that exogenously administered ABA renders rice hypersusceptible to infection, whereas chemical and genetic disruption of ABA biosynthesis and signaling, respectively, led to enhanced Xoo resistance. In addition, we found successful Xoo infection to be associated with extensive reprogramming of ABA biosynthesis and response genes, suggesting that ABA functions as a virulence factor for Xoo. Interestingly, several lines of evidence indicate that this immune-suppressive effect of ABA is due at least in part to suppression of SA-mediated defenses that normally serve to limit pathogen growth. Resistance induced by the ABA biosynthesis inhibitor fluridone, however, appears to operate in a SA-independent manner and is likely due to induction of non-specific physiological stress. Collectively, our findings favor a scenario whereby virulent Xoo hijacks the rice ABA machinery to cause disease and highlight the importance of ABA and its crosstalk with SA in shaping the outcome of rice-Xoo interactions.

  13. Repeated exposures to roadside particulate matter extracts suppresses pulmonary defense mechanisms, resulting in lipid and protein oxidative damage.

    Science.gov (United States)

    Pardo, Michal; Porat, Ziv; Rudich, Assaf; Schauer, James J; Rudich, Yinon

    2016-03-01

    Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The effect of water limitation on volatile emission, tree defense response, and brood success of Dendroctonus ponderosae in two pine hosts, lodgepole and jack pine

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    Inka eLusebrink

    2016-02-01

    Full Text Available The mountain pine beetle (MPB; Dendroctonus ponderosae has recently expanded its range from lodgepole pine forest into the lodgepole × jack pine hybrid zone in central Alberta, within which it has attacked pure jack pine. This study tested the effects of water limitation on tree defense response of mature lodgepole and jack pine (Pinus contorta and Pinus banksiana trees in the field. Tree defense response was initiated by inoculation of trees with the MPB-associated fungus Grosmannia clavigera and measured through monoterpene emission from tree boles and concentration of defensive compounds in phloem, needles, and necrotic tissues. Lodgepole pine generally emitted higher amounts of monoterpenes than jack pine; particularly from fungal-inoculated trees. Compared to non-inoculated trees, fungal inoculation increased monoterpene emission in both species, whereas water treatment had no effect on monoterpene emission. The phloem of both pine species contains (--α-pinene, the precursor of the beetle’s aggregation pheromone, however lodgepole pine contains two times as much as jack pine. The concentration of defensive compounds was 70-fold greater in the lesion tissue in jack pine, but only 10-fold in lodgepole pine compared to healthy phloem tissue in each species, respectively. Water-deficit treatment inhibited an increase of L-limonene as response to fungal inoculation in lodgepole pine phloem. The amount of myrcene in jack pine phloem was higher in water-deficit trees compared to ambient trees. Beetles reared in jack pine were not affected by either water or biological treatment, whereas beetles reared in lodgepole pine benefited from fungal inoculation by producing larger and heavier female offspring. Female beetles that emerged from jack pine bolts contained more fat than those that emerged from lodgepole pine, even though lodgepole pine phloem had a higher nitrogen content than jack pine phloem. These results suggest that jack pine chemistry

  15. A new lysozyme from the eastern oyster, Crassostrea virginica, and a possible evolutionary pathway for i-type lysozymes in bivalves from host defense to digestion

    Science.gov (United States)

    2010-01-01

    Background Lysozymes are enzymes that lyse bacterial cell walls, an activity widely used for host defense but also modified in some instances for digestion. The biochemical and evolutionary changes between these different functional forms has been well-studied in the c-type lysozymes of vertebrates, but less so in the i-type lysozymes prevalent in most invertebrate animals. Some bivalve molluscs possess both defensive and digestive lysozymes. Results We report a third lysozyme from the oyster Crassostrea virginica, cv-lysozyme 3. The chemical properties of cv-lysozyme 3 (including molecular weight, isoelectric point, basic amino acid residue number, and predicted protease cutting sites) suggest it represents a transitional form between lysozymes used for digestion and immunity. The cv-lysozyme 3 protein inhibited the growth of bacteria (consistent with a defensive function), but semi-quantitative RT-PCR suggested the gene was expressed mainly in digestive glands. Purified cv-lysozyme 3 expressed maximum muramidase activity within a range of pH (7.0 and 8.0) and ionic strength (I = 0.005-0.01) unfavorable for either cv-lysozyme 1 or cv-lysozyme 2 activities. The topology of a phylogenetic analysis of cv-lysozyme 3 cDNA (full length 663 bp, encoding an open reading frame of 187 amino acids) is also consistent with a transitional condition, as cv-lysozyme 3 falls at the base of a monophyletic clade of bivalve lysozymes identified from digestive glands. Rates of nonsynonymous substitution are significantly high at the base of this clade, consistent with an episode of positive selection associated with the functional transition from defense to digestion. Conclusion The pattern of molecular evolution accompanying the shift from defensive to digestive function in the i-type lysozymes of bivalves parallels those seen for c-type lysozymes in mammals and suggests that the lysozyme paralogs that enhance the range of physiological conditions for lysozyme activity may provide

  16. A new lysozyme from the eastern oyster, Crassostrea virginica, and a possible evolutionary pathway for i-type lysozymes in bivalves from host defense to digestion

    Directory of Open Access Journals (Sweden)

    Itoh Naoki

    2010-07-01

    Full Text Available Abstract Background Lysozymes are enzymes that lyse bacterial cell walls, an activity widely used for host defense but also modified in some instances for digestion. The biochemical and evolutionary changes between these different functional forms has been well-studied in the c-type lysozymes of vertebrates, but less so in the i-type lysozymes prevalent in most invertebrate animals. Some bivalve molluscs possess both defensive and digestive lysozymes. Results We report a third lysozyme from the oyster Crassostrea virginica, cv-lysozyme 3. The chemical properties of cv-lysozyme 3 (including molecular weight, isoelectric point, basic amino acid residue number, and predicted protease cutting sites suggest it represents a transitional form between lysozymes used for digestion and immunity. The cv-lysozyme 3 protein inhibited the growth of bacteria (consistent with a defensive function, but semi-quantitative RT-PCR suggested the gene was expressed mainly in digestive glands. Purified cv-lysozyme 3 expressed maximum muramidase activity within a range of pH (7.0 and 8.0 and ionic strength (I = 0.005-0.01 unfavorable for either cv-lysozyme 1 or cv-lysozyme 2 activities. The topology of a phylogenetic analysis of cv-lysozyme 3 cDNA (full length 663 bp, encoding an open reading frame of 187 amino acids is also consistent with a transitional condition, as cv-lysozyme 3 falls at the base of a monophyletic clade of bivalve lysozymes identified from digestive glands. Rates of nonsynonymous substitution are significantly high at the base of this clade, consistent with an episode of positive selection associated with the functional transition from defense to digestion. Conclusion The pattern of molecular evolution accompanying the shift from defensive to digestive function in the i-type lysozymes of bivalves parallels those seen for c-type lysozymes in mammals and suggests that the lysozyme paralogs that enhance the range of physiological conditions for

  17. Both MHC class I and class II molecules are required while MHC-I appears to play a critical role in host defense against primaryCoxiella burnetiiinfection.

    Science.gov (United States)

    Buttrum, Laura; Ledbetter, Lindsey; Cherla, Rama; Zhang, Yan; Mitchell, William J; Zhang, Guoquan

    2018-01-08

    To understand the role of class I major histocompatibility complex (MHC-I) and class II MHC (MHC-II) antigen presentation pathways in host defense against C. burnetii infection, we examined if MHC-I or MHC-II deficiency in mice would significantly influence their susceptibility to virulent C. burnetii Nine Mile phase I (NMI) infection. The results indicate that NMI infection induced more severe disease in both MHC-I deficient and MHC-II deficient mice compared to WT mice, while only MHC-I deficient mice developed a severe persistent infection and were unable to control bacterial replication. These results suggest that both MHC-I restricted CD8 + T cells and MHC-II restricted CD4 + T cells contribute to host defense against primary C. burnetii infection, while MHC-I restricted CD8 + T cells appear to play a more critical role in controlling bacterial replication. Additionally, although NMI infection induced more severe disease in TAP1 deficient mice than their WT counterparts, TAP1 deficiency in mice did not significantly influence their ability to eliminate C. burnetii This suggests that C. burnetii antigen presentation to CD8 + T cells by the MHC-I classical pathway may only partially depend on TAP1. Furthermore, granzyme B deficiency in mice did not significantly alter their susceptibility to C. burnetii infection, but perforin deficient mice were unable to control host inflammatory responses during primary C. burnetii infection. These results suggest that perforin, but not granzyme B, is required for C. burnetii antigen specific cytotoxic CD8 + T cells to control primary C. burnetii infection. Copyright © 2018 American Society for Microbiology.

  18. Endophytic Bacteria Suppress Bacterial Wilt of Tomato Caused by Ralstonia solanacearum and Activate Defense-related Metabolites

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    Fahime Safdarpour

    2017-12-01

    Full Text Available Introduction: Phytopathogenic microorganisms affect plant health and burden a major threat to food production and ecosystem stability. Increasing the use of chemical pesticides for plant diseases control causes several negative effects on human and environment health. Furthermore, increasing public awareness about the side effects of them led to a research to find alternatives for these products. One of the alternative methods is bio-control utilizing plant associated antagonistic microorganisms. Materials and methods: In this study, 80 endophytic bacteria were isolated from tomato tissues. Their antagonistic activity screened based on agar diffusion test, against tomato bacterial wilt disease (Ralstonia solanacearum. They were identified based on the morphological, biochemical properties and 16s rRNA sequence analyses. These strains were evaluated in greenhouse and tested for their ability to induce the production of defense-related enzymes in plants e.g. Peroxidase (PO, polyphenoloxidase (PPO and phenolics based on spectrophotometer method. Results: Results showed FS67, FS167 and FS184 strains had maximum inhibition zone forming. They identified as Pseudomonas mossellii, P. fuorescence and P. brassicacearum respectively. FS67 and FS167 strains significantly reduced disease in greenhouse. There was a significant increase in the activity of PO, PPO and phenolics in tomato plants treated with FS67, FS167 and pathogen. Discussion and conclusion: The present study has shown that P. mosselli and P. fuorescence might have the potential to control R. solanacearum. However, the good results obtained in vitro cannot be gained the same as those in greenhouse or field conditions. So, further experiments are needed to determine the effectiveness of these isolates under field conditions.This work support the view that increased defense enzymes activities could be involved, at least in part, in the beneficial effects of endophytic bacteria on plants growth

  19. Expression of Early Immune-Response Genes in Lepidopteran Host are Suppressed by Venom From an Endoparasitoid, Pteromalus puparum

    Science.gov (United States)

    The relationships between parasitoids and their insect hosts have attracted attention at two levels. First, the basic biology of host-parasitoid interactions is of fundamental interest. Second, parasitoids have tremendous potential as biological control agents in sustainable agriculture programs. Pt...

  20. Human and Animal Isolates of Yersinia enterocolitica Show Significant Serotype-Specific Colonization and Host-Specific Immune Defense Properties

    Science.gov (United States)

    Schaake, Julia; Kronshage, Malte; Uliczka, Frank; Rohde, Manfred; Knuuti, Tobias; Strauch, Eckhard; Fruth, Angelika; Wos-Oxley, Melissa

    2013-01-01

    Yersinia enterocolitica is a human pathogen that is ubiquitous in livestock, especially pigs. The bacteria are able to colonize the intestinal tract of a variety of mammalian hosts, but the severity of induced gut-associated diseases (yersiniosis) differs significantly between hosts. To gain more information about the individual virulence determinants that contribute to colonization and induction of immune responses in different hosts, we analyzed and compared the interactions of different human- and animal-derived isolates of serotypes O:3, O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and macrophages. The examined strains exhibited significant serotype-specific cell binding and entry characteristics, but adhesion and uptake into different host cells were not host specific and were independent of the source of the isolate. In contrast, survival and replication within macrophages and the induced proinflammatory response differed between murine, porcine, and human macrophages, suggesting a host-specific immune response. In fact, similar levels of the proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted by murine bone marrow-derived macrophages with all tested isolates, but the equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived macrophages was strongly serotype specific and considerably lower in O:3 than in O:8 strains. In addition, all tested Y. enterocolitica strains caused a considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by porcine than by murine macrophages. This could contribute to limiting the severity of the infection (in particular of serotype O:3 strains) in pigs, which are the primary reservoir of Y. enterocolitica strains pathogenic to humans. PMID:23959720

  1. Isolation of a potential biocontrol agent Paenibacillus polymyxa NSY50 from vinegar waste compost and its induction of host defense responses against Fusarium wilt of cucumber.

    Science.gov (United States)

    Du, Nanshan; Shi, Lu; Yuan, Yinghui; Sun, Jin; Shu, Sheng; Guo, Shirong

    2017-09-01

    Fusarium wilt caused by Fusarium oxysporum f. sp. cucumerinum (FOC) is one of the major destructive soil-borne diseases infecting cucumber. In this study, we screened 60 target strains isolated from vinegar waste compost, from which 10 antagonistic strains were identified to have the disease suppression capacity of bio-control agents. The 16S rDNA gene demonstrated that the biocontrol agents were Paenibacillus polymyxa (P. polymyxa), Bacillus amyloliquefaciens (B. amyloliquefaciens) and Bacillus licheniformis (B. licheniformis). Based on the results of antagonistic activity experiments and pot experiment, an interesting strain of P. polymyxa (named NSY50) was selected for further research. Morphological, physiological and biochemical characteristics indicated that this strain was positive for protease and cellulase and produced indole acetic acid (22.21±1.27μg mL -1 ) and 1-aminocyclopropane-1-carboxylate deaminase (ACCD). NSY50 can significantly up-regulate the expression level of defense related genes PR1 and PR5 in cucumber roots at the early stages upon challenge with FOC. However, the gene expression levels of a set of defense-related genes, such as the plant nucleotide-binding site (NBS)-leucine-rich repeat (LRR) gene family (e.g., Csa001236, Csa09775, Csa018159), 26kDa phloem protein (Csa001568, Csa003306), glutathione-S-transferase (Csa017734) and phenylalanine ammonia-lyase (Csa002864) were suppressed by pretreatment with NSY50 compared with the single challenge with FOC after nine days of inoculation. Of particular interest was the reduced expression of these genes at disease progression stages, which may be required for F. oxysporum dependent necrotrophic disease development. Copyright © 2017 Elsevier GmbH. All rights reserved.

  2. S100A8/A9 Is Not Involved in Host Defense against Murine Urinary Tract Infection

    NARCIS (Netherlands)

    Dessing, M.C.; Butter, L.M.; Teske, G.J.; Claessen, N.; van der Loos, C.M.; Vogl, T.; Roth, J.; van der Poll, T.; Florquin, S.; Leemans, J.C.

    2010-01-01

    Background: Inflammation is commonly followed by the release of endogenous proteins called danger associated molecular patterns (DAMPs) that are able to warn the host for eminent danger. S100A8/A9 subunits are DAMPs that belong to the S100 family of calcium binding proteins. S100A8/A9 complexes

  3. Chlorogenic Acid Attenuates High Mobility Group Box 1 (HMGB1) and Enhances Host Defense Mechanisms in Murine Sepsis

    Science.gov (United States)

    Lee, Chan-Ho; Yoon, Seong-Jin; Lee, Sun-Mee

    2012-01-01

    Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivo and prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders. PMID:23168580

  4. Ciprofloxacin Affects Host Cells by Suppressing Expression of the Endogenous Antimicrobial Peptides Cathelicidins and Beta-Defensin-3 in Colon Epithelia

    Directory of Open Access Journals (Sweden)

    Protim Sarker

    2014-07-01

    Full Text Available Antibiotics exert several effects on host cells including regulation of immune components. Antimicrobial peptides (AMPs, e.g., cathelicidins and defensins display multiple functions in innate immunity. In colonic mucosa, cathelicidins are induced by butyrate, a bacterial fermentation product. Here, we investigated the effect of antibiotics on butyrate-induced expression of cathelicidins and beta-defensins in colon epithelial cells. Real-time PCR analysis revealed that ciprofloxacin and clindamycin reduce butyrate-induced transcription of the human cathelicidin LL-37 in the colonic epithelial cell line HT-29. Suppression of LL-37 peptide/protein by ciprofloxacin was confirmed by Western blot analysis. Immunohistochemical analysis demonstrated that ciprofloxacin suppresses the rabbit cathelicidin CAP-18 in rectal epithelia of healthy and butyrate-treated Shigella-infected rabbits. Ciprofloxacin also down-regulated butyrate-induced transcription of the human beta-defensin-3 in HT-29 cells. Microarray analysis of HT-29 cells revealed upregulation by butyrate with subsequent down-regulation by ciprofloxacin of additional genes encoding immune factors. Dephosphorylation of histone H3, an epigenetic event provided a possible mechanism of the suppressive effect of ciprofloxacin. Furthermore, LL-37 peptide inhibited Clostridium difficile growth in vitro. In conclusion, ciprofloxacin and clindamycin exert immunomodulatory function by down-regulating AMPs and other immune components in colonic epithelial cells. Suppression of AMPs may contribute to the overgrowth of C. difficile, causing antibiotic-associated diarrhea.

  5. Subdued, a TMEM16 family Ca²⁺-activated Cl⁻channel in Drosophila melanogaster with an unexpected role in host defense.

    Science.gov (United States)

    Wong, Xiu Ming; Younger, Susan; Peters, Christian J; Jan, Yuh Nung; Jan, Lily Y

    2013-11-05

    TMEM16A and TMEM16B are calcium-activated chloride channels (CaCCs) with important functions in mammalian physiology. Whether distant relatives of the vertebrate TMEM16 families also form CaCCs is an intriguing open question. Here we report that a TMEM16 family member from Drosophila melanogaster, Subdued (CG16718), is a CaCC. Amino acid substitutions of Subdued alter the ion selectivity and kinetic properties of the CaCC channels heterologously expressed in HEK 293T cells. This Drosophila channel displays characteristics of classic CaCCs, thereby providing evidence for evolutionarily conserved biophysical properties in the TMEM16 family. Additionally, we show that knockout flies lacking subdued gene activity more readily succumb to death caused by ingesting the pathogenic bacteria Serratia marcescens, suggesting that subdued has novel functions in Drosophila host defense. DOI: http://dx.doi.org/10.7554/eLife.00862.001.

  6. Transcriptome Analysis Reveals Novel Entry Mechanisms and a Central Role of SRC in Host Defense during High Multiplicity Mycobacterial Infection.

    Directory of Open Access Journals (Sweden)

    Jay Zhang

    Full Text Available Mycobacterium tuberculosis (MTB infects an estimated one-third of the global population and is one of the main causes of mortality from an infectious agent. The characteristics of macrophages challenged by MTB with a high multiplicity of infection (MOI, which mimics both clinical disseminated infection and granuloma formation, are distinct from macrophages challenged with a low MOI. To better understand the cross talk between macrophage host cells and mycobacteria, we compared the transcription patterns of mouse macrophages infected with bacille Calmette-Guérin, H37Ra and M. smegmatis. Attention was focused on the changes in the abundance of transcripts related to immune system function. From the results of a transcriptome profiling study with a high mycobacterial MOI, we defined a pathogen-specific host gene expression pattern. The present study suggests that two integrins, ITGA5 and ITGAV, are novel cell surface receptors mediating mycobacterium entry into macrophages challenged with high MOI. Our results indicate that SRC likely plays a central role in regulating multiple unique signaling pathways activated by MTB infection. The integrated results increase our understanding of the molecular networks behind the host innate immune response and identify important targets that might be useful for the development of tuberculosis therapy.

  7. Innate Immune Memory Contributes to Host Defense against Recurrent Skin and Skin Structure Infections Caused by Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Chan, Liana C.; Chaili, Siyang; Filler, Scott G.; Miller, Lloyd S.; Solis, Norma V.; Wang, Huiyuan; Johnson, Colin W.; Lee, Hong K.; Diaz, Luis F.

    2016-01-01

    ABSTRACT Staphylococcus aureus is the leading cause of skin and skin structure infections (SSSI). The high frequency of recurring SSSI due to S. aureus, including methicillin-resistant S. aureus (MRSA) strains, despite high titers of specific antibodies and circulating T cells, implies that traditional adaptive immunity imparts incomplete protection. We hypothesized that innate immune memory contributes to the protective host defense against recurring MRSA infection. To test this hypothesis, SSSI was induced in wild-type and rag1−/− mice in the BALB/c and C57BL/6 backgrounds. Prior infection (priming) of wild-type and rag1−/− mice of either background afforded protection against repeat infection, as evidenced by reduced abscess severities and decreased CFU densities compared to those in naive controls. Interestingly, protection was greater on the previously infected flank than on the naive flank for wild-type and rag1−/− mice. For wild-type mice, protective efficacy corresponded to increased infiltration of neutrophils (polymorphonuclear leukocytes [PMN]), macrophages (MΦ), Langerin+ dendritic cells (LDC), and natural killer (NK) cells. Protection was associated with the induction of interleukin-17A (IL-17A), IL-22, and gamma interferon (IFN-γ) as well as the antimicrobial peptides CRAMP and mβD-3. Priming also protected rag1−/− mice against recurring SSSI, with increased MΦ and LDC infiltration and induction of IL-22, CRAMP, and mβD-3. These findings suggest that innate immune memory, mediated by specific cellular and molecular programs, likely contributes to the localized host defense in recurrent MRSA SSSI. These insights support the development of targeted immunotherapeutic strategies to address the challenge of MRSA infection. PMID:27849182

  8. Natural Killer Cell-Mediated Host Defense against Uropathogenic E. coli Is Counteracted by Bacterial HemolysinA-Dependent Killing of NK Cells

    Science.gov (United States)

    Gur, Chamutal; Coppenhagen-Glazer, Shunit; Rosenberg, Shilo; Yamin, Rachel; Enk, Jonatan; Glasner, Ariella; Bar-On, Yotam; Fleissig, Omer; Naor, Ronit; Abed, Jawad; Mevorach, Dror; Granot, Zvi; Bachrach, Gilad; Mandelboim, Ofer

    2013-01-01

    SUMMARY Uropathogenic Escherichia coli (UPEC) are a common cause of urinary tract infections (UTIs) in humans. While the importance of natural killer (NK) cells in innate immune protection against tumors and viral infections is well documented, their role in defense against bacterial infections is still emerging, and their involvement in UPEC-mediated UTI is practically unknown. Using a systematic mutagenesis approach, we found that UPEC adheres to NK cells primarily via its type I fimbriae and employs its hemolysinA toxin to kill NK cells. In the absence of hemolysinA, NK cells directly respond to the bacteria and secrete the cytokine TNF-α, which results in decreased bacterial numbers in vitro and reduction of bacterial burden in the infected bladders. Thus, NK cells control UPEC via TNF-α production, which UPEC counteracts by hemolysinA-mediated killing of NK cells, representing a previously unrecognized host defense and microbial counterattack mechanism in the context of UTI. PMID:24331464

  9. Genome wide expression profiling reveals suppression of host defence responses during colonisation by Neisseria meningitides but not N. lactamica.

    Directory of Open Access Journals (Sweden)

    Hazel En En Wong

    Full Text Available Both Neisseria meningitidis and the closely related bacterium Neisseria lactamica colonise human nasopharyngeal mucosal surface, but only N. meningitidis invades the bloodstream to cause potentially life-threatening meningitis and septicaemia. We have hypothesised that the two neisserial species differentially modulate host respiratory epithelial cell gene expression reflecting their disease potential. Confluent monolayers of 16HBE14 human bronchial epithelial cells were exposed to live and/or dead N. meningitidis (including capsule and pili mutants and N. lactamica, and their transcriptomes were compared using whole genome microarrays. Changes in expression of selected genes were subsequently validated using Q-RT-PCR and ELISAs. Live N. meningitidis and N. lactamica induced genes involved in host energy production processes suggesting that both bacterial species utilise host resources. N. meningitidis infection was associated with down-regulation of host defence genes. N. lactamica, relative to N. meningitidis, initiates up-regulation of proinflammatory genes. Bacterial secreted proteins alone induced some of the changes observed. The results suggest N. meningitidis and N. lactamica differentially regulate host respiratory epithelial cell gene expression through colonisation and/or protein secretion, and that this may contribute to subsequent clinical outcomes associated with these bacteria.

  10. Francisella tularensis subsp. tularensis induces a unique pulmonary inflammatory response: role of bacterial gene expression in temporal regulation of host defense responses.

    Directory of Open Access Journals (Sweden)

    Kathie-Anne Walters

    Full Text Available Pulmonary exposure to Francisella tularensis is associated with severe lung pathology and a high mortality rate. The lack of induction of classical inflammatory mediators, including IL1-β and TNF-α, during early infection has led to the suggestion that F. tularensis evades detection by host innate immune surveillance and/or actively suppresses inflammation. To gain more insight into the host response to Francisella infection during the acute stage, transcriptomic analysis was performed on lung tissue from mice exposed to virulent (Francisella tularensis ssp tularensis SchuS4. Despite an extensive transcriptional response in the lungs of animals as early as 4 hrs post-exposure, Francisella tularensis was associated with an almost complete lack of induction of immune-related genes during the initial 24 hrs post-exposure. This broad subversion of innate immune responses was particularly evident when compared to the pulmonary inflammatory response induced by other lethal (Yersinia pestis and non-lethal (Legionella pneumophila, Pseudomonas aeruginosa pulmonary infections. However, the unique induction of a subset of inflammation-related genes suggests a role for dysregulation of lymphocyte function and anti-inflammatory pathways in the extreme virulence of Francisella. Subsequent activation of a classical inflammatory response 48 hrs post-exposure was associated with altered abundance of Francisella-specific transcripts, including those associated with bacterial surface components. In summary, virulent Francisella induces a unique pulmonary inflammatory response characterized by temporal regulation of innate immune pathways correlating with altered bacterial gene expression patterns. This study represents the first simultaneous measurement of both host and Francisella transcriptome changes that occur during in vivo infection and identifies potential bacterial virulence factors responsible for regulation of host inflammatory pathways.

  11. Albugo-imposed changes to tryptophan-derived antimicrobial metabolite biosynthesis may contribute to suppression of non-host resistance to Phytophthora infestans in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Prince, David C.; Rallapalli, Ghanasyam; Xu, Deyang

    2017-01-01

    -derived antimicrobial compounds enables P. infestans colonization of Arabidopsis, although to a lesser extent than Albugo-infected tissue. A. laibachii also suppresses a subset of genes regulated by salicylic acid; however, salicylic acid plays only a minor role in non-host resistance to P. infestans. CONCLUSIONS......: Albugo sp. alter tryptophan-derived metabolites and suppress elements of the responses to salicylic acid in Arabidopsis. Albugo sp. imposed alterations in tryptophan-derived metabolites may play a role in Arabidopsis non-host resistance to P. infestans. Understanding the basis of non-host resistance...

  12. Blumeria graminis secretes an extracellular catalase during infection of barley: potential role in suppression of host defence.

    Science.gov (United States)

    Zhang, Ziguo; Henderson, Catherine; Gurr, Sarah Jane

    2004-11-01

    SUMMARY The obligate biotrophic fungal pathogen of barley, Blumeria graminis f.sp. hordei (Bgh), elicits a burst of H(2)O(2) in its host barley at sites of germ tube invasion. To evaluate whether this specialized pathogen has any antioxidant response to this oxidative burst, the Bgh catB gene was characterized and transcript-profiled together with other genes implicated in the management of oxidative stress (catalase-peroxidase, cpx; glutathione peroxidase, gpx; superoxide dismutase, sod1) and in comparison with the constitutively expressed Bghbeta-tubulin and elongation factor1 (ef1) genes. Gel-based and real-time RT-PCR revealed enhanced numbers of catB transcripts at mature primary germ tube and appressorium germ tube (AGT) stages in a susceptible host. Moreover, an anti-CATB polyclonal antibody, from Aspergillus fumigatus, which recognizes both native and recombinant Bgh CATB, revealed an intense circle of immunofluorescence at the host-pathogen interface at the AGT tip and within the halo area surrounding the host papilla. A new diaminobenzidine-based 'scavenger' assay revealed areas of H(2)O(2) clearing at sites of fungal invasion, provoking speculation that Bgh catalase activity may contribute to pathogenicity in Bgh.

  13. Adjustment of host cells for accommodation of symbiotic bacteria: vacuole defunctionalization, HOPS suppression, and TIP1g retargeting in Medicago

    NARCIS (Netherlands)

    Gavrin, A.Y.; Kaiser, B.N.; Geiger, D.; Tyerman, S.D.; Wen, Z.; Bisseling, T.; Fedorova, E.E.

    2014-01-01

    In legume–rhizobia symbioses, the bacteria in infected cells are enclosed in a plant membrane, forming organelle-like compartments called symbiosomes. Symbiosomes remain as individual units and avoid fusion with lytic vacuoles of host cells. We observed changes in the vacuole volume of infected

  14. Effect of Probiotic Bacteria on Microbial Host Defense, Growth, and Immune Function in Human Immunodeficiency Virus Type-1 Infection

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    Stig Bengmark

    2011-12-01

    Full Text Available The hypothesis that probiotic administration protects the gut surface and could delay progression of Human Immunodeficiency Virus type1 (HIV-1 infection to the Acquired Immunodeficiency Syndrome (AIDS was proposed in 1995. Over the last five years, new studies have clarified the significance of HIV-1 infection of the gut associated lymphoid tissue (GALT for subsequent alterations in the microflora and breakdown of the gut mucosal barrier leading to pathogenesis and development of AIDS. Current studies show that loss of gut CD4+ Th17 cells, which differentiate in response to normal microflora, occurs early in HIV-1 disease. Microbial translocation and suppression of the T regulatory (Treg cell response is associated with chronic immune activation and inflammation. Combinations of probiotic bacteria which upregulate Treg activation have shown promise in suppressing pro inflammatory immune response in models of autoimmunity including inflammatory bowel disease and provide a rationale for use of probiotics in HIV-1/AIDS. Disturbance of the microbiota early in HIV-1 infection leads to greater dominance of potential pathogens, reducing levels of bifidobacteria and lactobacillus species and increasing mucosal inflammation. The interaction of chronic or recurrent infections, and immune activation contributes to nutritional deficiencies that have lasting consequences especially in the HIV-1 infected child. While effective anti-retroviral therapy (ART has enhanced survival, wasting is still an independent predictor of survival and a major presenting symptom. Congenital exposure to HIV-1 is a risk factor for growth delay in both infected and non-infected infants. Nutritional intervention after 6 months of age appears to be largely ineffective. A meta analysis of randomized, controlled clinical trials of infant formulae supplemented with Bifidobacterium lactis showed that weight gain was significantly greater in infants who received B. lactis compared to

  15. Parasitism of Lacanobia oleracea (lepidoptera) by the ectoparasitic wasp, Eulophus pennicornis, disrupts the cytoskeleton of host haemocytes and suppresses encapsulation in vivo.

    Science.gov (United States)

    Richards, Elaine H; Edwards, John P

    2002-02-01

    Parasitism of Lacanobia oleracea larvae by the ectoparasitic wasp Eulophus pennicornis suppressed host haemocyte-mediated encapsulation of Sephadex DEAE A-25 beads in vivo. Beads dissected out of parasitized larvae had fewer haemocytes associated with them. Moreover, those haemocytes that were associated with the beads tended to retain a rounded configuration and rarely flattened. Similar results were obtained using in vitro encapsulation assays. SDS PAGE indicated that for parasitized and PBS injected larvae, there were some differences in the plasma proteins that bound to Sephadex DEAE A-25 beads, suggesting that parasitism-mediated changes to host plasma proteins might contribute to the differences in the encapsulation response occurring in these larvae. However, in vitro encapsulation assays using beads that had been pre-incubated in plasma from parasitized and unparasitized larvae, demonstrated that major differences in the extent of encapsulation did not occur. These results, plus in vitro haemocyte attachment and spreading assays, suggest that parasitism-mediated suppression of encapsulation is primarily due to reductions in the ability of host haemocytes to attach to (i.e., recognize) and flatten over non-self surfaces and other haemocytes. This proposal is corroborated by staining of actin in the haemocyte cytoskeleton by FITC-labelled phalloidin, which indicated that parasitism disrupts the formation of stress fibers and focal adhesions in plasmatocytes. By contrast, experimental injection of adult female wasp venom into unparasitized L. oleracea larvae had no significant effect on in vivo encapsulation responses or the haemocyte cytoskeleton. Arch. Insect Biochem. Physiol. 49:108-124, 2002. Published 2002 Wiley-Liss, Inc.

  16. [Effect of cysteine ethylester hydrochloride (Cystanin) on host defense mechanisms (III): Potentiating effects on phagocytosis and nitroblue tetrazolium (NBT) reduction by leukocytes of mice and guinea pigs].

    Science.gov (United States)

    Hisadome, M; Nakamura, Y; Okumoto, T; Ikegami, K

    1986-11-01

    ICR mice were treated orally with cysteine ethylester hydrochloride (ethylcysteine, 10 and 100 mg/kg) immediately before the intraperitoneal injection of yeast particles. This agent significantly potentiated phagocytosis of yeast particles by peritoneal polymorphonuclear leukocytes in mice obtained 2 hr after the yeast injection, and the treatment with this agent (3 and 30 mg/kg, p.o.) 4 hr before the injection of yeast potentiated phagocytosis of yeast particles by mouse peritoneal leukocytes. This agent (30 mg/kg, p.o.) restored the suppression of phagocytosis of mouse leukocytes by the intraperitoneal administration of cyclophosphamide (30 mg/kg, i.p.) 24 hr before the yeast injection. This agent (10-100 mg/kg, p.o.) had no effect on the decrease of peripheral leukocyte number in irradiated mice (560 rad), but restored the suppression of phagocytosis, nitroblue tetrazolium (NBT) reduction and stimulated NBT reduction by the addition of lipopolysaccharide. Furthermore, this agent (3-30 mg/kg, p.o.) potentiated phagocytosis, NBT reduction and stimulated NBT reduction of peripheral leukocytes obtained from guinea pigs 2 and 6 hr after ethylcysteine treatment. It is suggested that ethylcysteine potentiates phagocytosis and NBT reduction of leukocytes in animals, and it restores phagocytosis and NBT reduction inhibited by the treatment with cyclophosphamide or X-ray irradiation. It may be possible that this stimulating effect of ethylcysteine could be at least in part involved in the stimulation of nonspecific resistance to infection in the compromised host.

  17. Mistletoe infection alters the transpiration flow path and suppresses water regulation of host trees during extreme events

    Science.gov (United States)

    Griebel, A.; Maier, C.; Barton, C. V.; Metzen, D.; Renchon, A.; Boer, M. M.; Pendall, E.

    2017-12-01

    Mistletoe is a globally distributed group of parasitic plants that infiltrates the vascular tissue of its host trees to acquire water, carbon and nutrients, making it a leading agent of biotic disturbance. Many mistletoes occur in water-limited ecosystems, thus mistletoe infection in combination with increased climatic stress may exacerbate water stress and potentially accelerate mortality rates of infected trees during extreme events. This is an emerging problem in Australia, as mistletoe distribution is increasing and clear links between mistletoe infection and mortality have been established. However, direct observations about how mistletoes alter host physiological processes during extreme events are rare, which impedes our understanding of mechanisms underlying increased tree mortality rates. We addressed this gap by continuously monitoring stem and branch sap flow and a range of leaf traits of infected and uninfected trees of two co-occurring eucalypt species during a severe heatwave in south-eastern Australia. We demonstrate that mistletoes' leaf water potentials were maintained 30% lower than hosts' to redirect the trees' transpiration flow path towards mistletoe leaves. Eucalypt leaves reduced water loss through stomatal regulation when atmospheric dryness exceeded 2 kPa, but the magnitude of stomatal regulation in non-infected eucalypts differed by species (between 40-80%). Remarkably, when infected, sap flow rates of stems and branches of both eucalypt species remained unregulated even under extreme atmospheric dryness (>8 kPa). Our observations indicate that excessive water use of mistletoes likely increases xylem cavitation rates in hosts during prolonged droughts and supports that hydraulic failure contributes to increased mortality of infected trees. Hence, in order to accurately model the contribution of biotic disturbances to tree mortality under a changing climate, it will be crucial to increase our process-based understanding of the interaction

  18. Effects of minimal exposures to atmospheric pressure plasma on the activity of Salmonella Typhimurium: Deactivation of bacterial motility and suppression of host-cell invasion.

    Science.gov (United States)

    Park, Jin-Sung; Kim, Kijung; Han, Je-Hyun; Gweon, Bomi; Ko, Ung Hyun; Yoo, Suk Jae; Choe, Wonho; Shin, Jennifer H

    2016-09-01

    Atmospheric pressure plasma (APP) has been shown effective in sterilization by reducing the number of viable microbes during surface cleaning, food processing, or human tissue treatment. For safe conduct, the majority of previous research focused on complete abolition of microbes, which may require severe treatments. Our aim is to investigate the minimal treatment conditions necessary for effective inactivation of bacteria in such a manner that the APP treated bacteria would not be able to harm the host cells. For this, we ought to identify the objective criteria to make the bacteria dysfunctional. We choose the motile properties and the host-cell invasion capability as two measures to quantify the pathogenic state of bacteria. In this paper, we investigated how the APP treatment in a minimal dosage affects the activity of Salmonella Typhimurium. At 100 W and 15 kHz for 20 s, the APP treatment effectively suppressed active "run and tumble" type motility and induced formation of abnormally long structures. With 20 s exposure, the bacterial cells failed to cause pyroptosis in the host cells with >90% survival after 12 h of co-incubation. Our results suggest novel measures to evaluate the functional pathogenic state for identifying safe APP treatment conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer.

    Science.gov (United States)

    Dan, Zhaoling; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Zou, Lili; Zeng, Lijuan; Xu, Yan; Yin, Qi; Xu, Minghua; Zhong, Dafang; Yu, Haijun; Shen, Qi; Zhang, Pengcheng; Li, Yaping

    2016-01-01

    Cancer metastasis is the leading reason for the high mortality of breast cancer. Herein, we report on a pH-responsive host-guest nanosystem of succinobucol (PHN) with pH-stimuli controlled drug release behavior to improve the therapeutic efficacy on lung metastasis of breast cancer. PHN was composed of the host polymer of β-cyclodextrin linked with multiple arms of N,N-diisopropylethylenediamine (βCD-DPA), the guest polymer of adamantyl end-capped methoxy poly(ethylene glycol) (mPEG-Ad), and the active agent of succinobucol. PHN comprises nanometer-sized homogenous spherical particles, and exhibits specific and rapid drug release in response to the intracellular acidic pH-stimuli. Then, the anti-metastatic efficacy of PHN is measured in metastatic 4T1 breast cancer cells, which effectively confirms the superior inhibitory effects on cell migration and invasion activities, VCAM-1 expression and cell-cell binding of RAW 264.7 to 4T1 cells. Moreover, PHN can be specifically delivered to the sites of metastatic nodules in lungs, and result in an obviously improved therapeutic efficacy on lung metastasis of breast cancer. Thereby, the pH-responsive host-guest nanosystem can be a promising drug delivery platform for effective treatment of cancer metastasis.

  20. Fungal colonization and host defense reactions in Ulmus americana callus cultures inoculated with Ophiostoma novo-ulmi.

    Science.gov (United States)

    Aoun, Mirella; Rioux, Danny; Simard, Marie; Bernier, Louis

    2009-06-01

    The host-pathogen interaction leading to Dutch elm disease was analyzed using histo- and cyto-chemical tests in an in vitro system. Friable and hard susceptible Ulmus americana callus cultures were inoculated with the highly aggressive pathogen Ophiostoma novo-ulmi. Inoculated callus tissues were compared with water-treated callus tissues and studied with light microscopy (LM), transmission-electron microscopy (TEM), and scanning-electron microscopy (SEM). New aspects of this interaction are described. These include the histological observation, for the first time in plant callus cultures, of suberin with its typical lamellar structure in TEM and the intracellular presence of O. novo-ulmi. Expression of the phenylalanine ammonia lyase gene, monitored by real-time quantitative polymerase chain reaction, was correlated with the accumulation of suberin, phenols, and lignin in infected callus cultures. This study validates the potential use of the in vitro system for genomic analyses aimed at identifying genes expressed during the interaction in the Dutch elm disease pathosystem.

  1. Loss of the innate immunity negative regulator IRAK-M leads to enhanced host immune defense against tumor growth

    Science.gov (United States)

    Xie, Qifa; Gan, Lu; Wang, Jianxia; Wilson, Ingred; Li, Liwu

    2010-01-01

    IRAK-M is a negative regulator of innate immunity signaling processes. Although attenuation of innate immunity may help to prevent excessive inflammation, it may also lead to compromised immune surveillance of tumor cells and contribute to tumor formation and growth. Here, we demonstrate that IRAK-M−/− mice are resistant to tumor growth upon inoculation with transplantable tumor cells. Immune cells from IRAK-M−/− mice are responsible for the anti-tumor effect, since adoptive transfer of splenocytes from IRAK-M−/− mice to wild type mice can transfer the tumor-resistant phenotype. Upon tumor cell challenge, there are elevated populations of CD4+ and CD8+ T cells and a decreased population of CD4+ CD25+Foxp3+ regulatory T cells in IRAK-M −/− splenocytes. Furthermore, we observe that IRAK-M deficiency leads to elevated proliferation and activation of T cells and B cells. Enhanced NFκB activation directly caused by IRAK-M deficiency may explain elevated activation of T and B cells. In addition, macrophages from IRAK-M−/− mice exhibit enhanced phagocytic function toward acetylated LDL and apoptotic thymocytes. Collectively, we demonstrate that IRAK-M is directly involved in the regulation of both innate and adaptive immune signaling processes, and deletion of IRAK-M enhances host anti-tumor immune response. PMID:17477969

  2. A hydrophobic anchor mechanism defines a deacetylase family that suppresses host response against YopJ effectors.

    Science.gov (United States)

    Bürger, Marco; Willige, Björn C; Chory, Joanne

    2017-12-19

    Several Pseudomonas and Xanthomonas species are plant pathogens that infect the model organism Arabidopsis thaliana and important crops such as Brassica. Resistant plants contain the infection by rapid cell death of the infected area through the hypersensitive response (HR). A family of highly related α/β hydrolases is involved in diverse processes in all domains of life. Functional details of their catalytic machinery, however, remained unclear. We report the crystal structures of α/β hydrolases representing two different clades of the family, including the protein SOBER1, which suppresses AvrBsT-incited HR in Arabidopsis. Our results reveal a unique hydrophobic anchor mechanism that defines a previously unknown family of protein deacetylases. Furthermore, this study identifies a lid-loop as general feature for substrate turnover in acyl-protein thioesterases and the described family of deacetylases. Furthermore, we found that SOBER1's biological function is not restricted to Arabidopsis thaliana and not limited to suppress HR induced by AvrBsT.

  3. ABA suppresses Botrytis cinerea elicited NO production in tomato to influence H2O2 generation and increase host susceptibility

    Directory of Open Access Journals (Sweden)

    Anushen eSivakumaran

    2016-05-01

    Full Text Available Abscisic acid (ABA production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with NO in tomato following challenge with the ABA-synthesising pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production – an established mediator of defence against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA (abscisic acid, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS generation but this was reduced in both L-NAME and ABA treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production.

  4. Field trials of fatty acids and geraniol applied to cattle for suppression of horn flies, Haematobia irritans (Diptera: Muscidae), with observations on fly defensive behaviors.

    Science.gov (United States)

    Mullens, Bradley A; Watson, D Wes; Gerry, Alec C; Sandelin, Broc A; Soto, Diane; Rawls, Diana; Denning, Steve; Guisewite, Lena; Cammack, Jonathan

    2017-10-15

    Adult horn fly populations were tracked on cattle for 2-week periods before, during and after multiple treatments (every 3-4days) with two repellents in a mineral oil carrier. Cattle were sprayed four times in a two-week period either with 2% geraniol (125ml/cow) or a 15% mixture of short chain fatty acids (C8-C9-C10)(250ml/cow), and there were untreated control cattle. Trials were conducted in California and North Carolina for 3 summers. Short-term fly counts (same day) on treated cattle were reduced by 61-99%, depending on material and trial, and the fatty acid mixture provided better control than geraniol. Horn fly counts were suppressed for 1-3 d and rebounded somewhat after both treatments. Consecutive treatments showed evidence of persistent impact in California where herds were more isolated. Rebounds to pre-treatment levels 3-4 d after treatment occurred more often in North Carolina, where other infested cattle were closer to treated herds. By 3-4 d post-treatment, horn flies were reduced by 29-61% in California and 0-83% in North Carolina, relative to pre-treatment. Background behavior frequencies were assessed from hundreds of counts on untreated, infested California cattle, where horn flies were the only abundant biting fly. Behavior averages were 16.5 tail flicks, 7.6 skin twitches, 1.2 head throws, or 0.2 leg stamps per 2min observation period. At horn fly densities from about 200 to more than 1000 flies per animal (moderate to high numbers), fly defensive behaviors on control cattle were poorly related (or unrelated) to fly numbers. Immediately after repellent application, however, flies were almost absent and behavior frequencies dropped distinctly. Cattle fly defensive behaviors therefore seem to be quite sensitive to low (less than 100 flies/animal) horn fly densities, and behaviors would be a poor quantitative tool to track fly stress at moderate densities and above. Both geraniol and the fatty acids show promise for horn fly control, especially

  5. Molecular identification and functional delineation of a glutathione reductase homolog from disk abalone (Haliotis discus discus): Insights as a potent player in host antioxidant defense.

    Science.gov (United States)

    Herath, H M L P B; Wickramasinghe, P D S U; Bathige, S D N K; Jayasooriya, R G P T; Kim, Gi-Young; Park, Myoung Ae; Kim, Chul; Lee, Jehee

    2017-01-01

    : Vibrio parahaemolyticus, Listeria monocytogenes, and lipopolysaccharide (LPS), thus indicating its possible involvement in host defense mechanisms during pathogenic infections. Taken together, the results of the current study suggest that AbGSR plays an important role in antioxidant-mediated host defense mechanisms and also provide insights into the immunological contribution of AbGSR. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Ulva lactuca polysaccharides prevent Wistar rat breast carcinogenesis through the augmentation of apoptosis, enhancement of antioxidant defense system, and suppression of inflammation

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    Abd-Ellatef GF

    2017-02-01

    cytokines tumor necrosis factor-α and nitric oxide were significantly ameliorated in DMBA-administered rats treated with ulvan polysaccharides as compared to DMBA-administered control. Conclusion: In conclusion, ulvan polysaccharides at the level of initiation and promotion might have potential chemopreventive effects against breast carcinogenesis. These preventive effects may be mediated through the augmentation of apoptosis, suppression of oxidative stress and inflammation, and enhancement of antioxidant defense system. Keywords: breast carcinogenesis, cancer initiation, cancer promotion, Ulva lactuca polysaccharides, DMBA, oxidative stress, apoptosis

  7. Differential Regulation of Mas-Related G Protein-Coupled Receptor X2-Mediated Mast Cell Degranulation by Antimicrobial Host Defense Peptides and Porphyromonas gingivalis Lipopolysaccharide.

    Science.gov (United States)

    Gupta, Kshitij; Idahosa, Chizobam; Roy, Saptarshi; Lee, Donguk; Subramanian, Hariharan; Dhingra, Anuradha; Boesze-Battaglia, Kathleen; Korostoff, Jonathan; Ali, Hydar

    2017-10-01

    Porphyromonas gingivalis is a keystone pathogen that contributes to periodontal pathogenesis by disrupting host-microbe homeostasis and promoting dysbiosis. The virulence of P. gingivalis likely reflects an alteration in the lipid A composition of its lipopolysaccharide (LPS) from the penta-acylated ( Pg LPS 1690 ) to the tetra-acylated ( Pg LPS 1435/1449 ) form. Mast cells play an important role in periodontitis, but the mechanisms of their activation and regulation remain unknown. The expression of epithelium- and neutrophil-derived host defense peptides (HDPs) (LL-37 and human β-defensin-3), which activate mast cells via Mas-related G protein-coupled receptor X2 (MRGPRX2), is increased in periodontitis. We found that MRGPRX2-expressing mast cells are present in normal gingiva and that their numbers are elevated in patients with chronic periodontitis. Furthermore, HDPs stimulated degranulation in a human mast cell line (LAD2) and in RBL-2H3 cells stably expressing MRGPRX2 (RBL-MRGPRX2). Pg LPS 1690 caused substantial inhibition of HDP-induced mast cell degranulation, but Pg LPS 1435/1449 had no effect. A fluorescently labeled HDP (FAM-LL-37) bound to RBL-MRGPRX2 cells, and Pg LPS 1690 inhibited this binding, but Pg LPS 1435/1449 had no effect. These findings suggest that low-level inflammation induced by HDP/MRGPRX2-mediated mast cell degranulation contributes to gingival homeostasis but that sustained inflammation due to elevated levels of both HDPs and MRGPRX2-expressing mast cells promotes periodontal disease. Furthermore, differential regulation of HDP-induced mast cell degranulation by Pg LPS 1690 and Pg LPS 1435/1449 may contribute to the modulation of disease progression. Copyright © 2017 American Society for Microbiology.

  8. Identification of a novel molluscan short-type peptidoglycan recognition protein in disk abalone (Haliotis discus discus) involved in host antibacterial defense.

    Science.gov (United States)

    Premachandra, H K A; Elvitigala, Don Anushka Sandaruwan; Whang, Ilson; Lee, Jehee

    2014-07-01

    Peptidoglycan recognition proteins (PGRPs) are a widely studied group of pattern recognition receptors found in invertebrate as well as vertebrate lineages, and are involved in bacterial pathogen sensing. However, in addition to this principal role, they can also function in multiple host defense processes, including cell phagocytosis and hydrolysis of peptidoglycans (PGNs). In this study, a novel invertebrate short-type PGRP was identified in disk abalone (Haliotis discus discus) designated as AbPGRP. The complete coding sequence of AbPGRP was 534 bp, encoding a 178-amino acid protein with a predicted molecular mass of 20 kDa. The AbPGRP gene had a bipartite arrangement consisting of two exons separated by a single intron. Homology analysis revealed that AbPGRP shares conserved features, including amino acid residues critical for substrate and ion binding as well as for its amidase activity, with homologs of other species. Phylogenetic analysis of AbPGRP revealed that it likely evolved from a common ancestor of invertebrates, having significant homology with other molluscan PGRPs. Recombinant AbPGRP exhibited detectable, dose-dependent PGN-hydrolyzing activity with the presence of Zn(2+), and strong antibacterial activity against Vibrio tapetis, consistent with the functional properties previously reported for PGRPs in other mollusks. Moreover, AbPGRP transcription was induced upon treatment of healthy abalones with bacterial peptidoglycan and lipopolysaccharide, although the expression profiles differed with treatment, suggesting a capacity for discriminating between bacterial pathogens through molecular pattern recognition. Collectively, the findings of this study indicate that AbPGRP is a true homolog of invertebrate PGRPs and likely plays an indispensable role in host immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Aphanomyces euteiches cell wall fractions containing novel glucan-chitosaccharides induce defense genes and nuclear calcium oscillations in the plant host Medicago truncatula.

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    Amaury Nars

    Full Text Available N-acetylglucosamine-based saccharides (chitosaccharides are components of microbial cell walls and act as molecular signals during host-microbe interactions. In the legume plant Medicago truncatula, the perception of lipochitooligosaccharide signals produced by symbiotic rhizobia and arbuscular mycorrhizal fungi involves the Nod Factor Perception (NFP lysin motif receptor-like protein and leads to the activation of the so-called common symbiotic pathway. In rice and Arabidopsis, lysin motif receptors are involved in the perception of chitooligosaccharides released by pathogenic fungi, resulting in the activation of plant immunity. Here we report the structural characterization of atypical chitosaccharides from the oomycete pathogen Aphanomyces euteiches, and their biological activity on the host Medicago truncatula. Using a combination of biochemical and biophysical approaches, we show that these chitosaccharides are linked to β-1,6-glucans, and contain a β-(1,3;1,4-glucan backbone whose β-1,3-linked glucose units are substituted on their C-6 carbon by either glucose or N-acetylglucosamine residues. This is the first description of this type of structural motif in eukaryotic cell walls. Glucan-chitosaccharide fractions of A. euteiches induced the expression of defense marker genes in Medicago truncatula seedlings independently from the presence of a functional Nod Factor Perception protein. Furthermore, one of the glucan-chitosaccharide fractions elicited calcium oscillations in the nucleus of root cells. In contrast to the asymmetric oscillatory calcium spiking induced by symbiotic lipochitooligosaccharides, this response depends neither on the Nod Factor Perception protein nor on the common symbiotic pathway. These findings open new perspectives in oomycete cell wall biology and elicitor recognition and signaling in legumes.

  10. Glycomic and glycoproteomic analysis of serum from patients with stomach cancer reveals potential markers arising from host defense response mechanisms.

    Science.gov (United States)

    Bones, Jonathan; Byrne, Jennifer C; O'Donoghue, Niaobh; McManus, Ciara; Scaife, Caitriona; Boissin, Herve; Nastase, Anca; Rudd, Pauline M

    2011-03-04

    Despite the reduced incidence of gastric cancer in the developed world, a diagnosis of stomach carcinoma still carries a poor prognosis due to the asymptomatic nature of the disease in the early stages, subsequent advanced stage diagnosis, and a low 5 year survival rate. Endoscopy remains the primary standard for diagnosis of stomach carcinoma and the current marker, carbohydrate antigen 19-9 (CA19-9) lacks the levels of sensitivity and specificity required in order to make it clinically useful for diagnostic monitoring. Therefore, there is a current need for additional markers to improve the diagnostic accuracy for the early stages of stomach cancer. Together, glycomic, proteomic, and glycoproteomic analyses of serum have the potential to identify such probable markers. A discovery study is reported here using preoperative serum from 80 stomach cancer patients, 10 patients bearing benign stomach disease, and 20 matched controls. Glycomic analysis of the total and immunoaffinity depleted serum revealed statistically significant increases in the levels of sialyl Lewis X epitopes (SLe(X)) present on triantennary glycans accompanied by increased levels of core fucosylated agalactosyl biantennary glycans present on IgG (referred to as the IgG G0 glycoform) which are associated with increasing disease pathogenesis. Protein expression analysis using 2D-DiGE returned a number of differentially expressed protein candidates in the depleted serum, many of which were shown to carry triantennary SLe(X) during subsequent glycomic investigations. Biological pathway analysis of the experimental data returned complement activation and acute phase response signaling as the most significantly altered pathways in the stomach cancer patient serum. Upon the basis of these findings, it is suggested that increased expression of IgG G0 and complement activation are a host response to the presence of the stomach tumor while the increased expression of SLe(X) and acute phase response

  11. Pharmacological Inhibition of Host Heme Oxygenase-1 Suppresses Mycobacterium tuberculosis Infection In Vivo by a Mechanism Dependent on T Lymphocytes

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    Diego L. Costa

    2016-10-01

    Full Text Available Heme oxygenase-1 (HO-1 is a stress response antioxidant enzyme which catalyzes the degradation of heme released during inflammation. HO-1 expression is upregulated in both experimental and human Mycobacterium tuberculosis infection, and in patients it is a biomarker of active disease. Whether the enzyme plays a protective versus pathogenic role in tuberculosis has been the subject of debate. To address this controversy, we administered tin protoporphyrin IX (SnPPIX, a well-characterized HO-1 enzymatic inhibitor, to mice during acute M. tuberculosis infection. These SnPPIX-treated animals displayed a substantial reduction in pulmonary bacterial loads comparable to that achieved following conventional antibiotic therapy. Moreover, when administered adjunctively with antimycobacterial drugs, the HO-1 inhibitor markedly enhanced and accelerated pathogen clearance. Interestingly, both the pulmonary induction of HO-1 expression and the efficacy of SnPPIX treatment in reducing bacterial burden were dependent on the presence of host T lymphocytes. Although M. tuberculosis expresses its own heme-degrading enzyme, SnPPIX failed to inhibit its enzymatic activity or significantly restrict bacterial growth in liquid culture. Together, the above findings reveal mammalian HO-1 as a potential target for host-directed monotherapy and adjunctive therapy of tuberculosis and identify the immune response as a critical regulator of this function.

  12. Metalloprotease NleC suppresses host NF-κB/inflammatory responses by cleaving p65 and interfering with the p65/RPS3 interaction.

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    Andrea Hodgson

    2015-03-01

    Full Text Available Attaching/Effacing (A/E pathogens including enteropathogenic Escherichia coli (EPEC, enterohemorrhagic E. coli (EHEC and the rodent equivalent Citrobacter rodentium are important causative agents of foodborne diseases. Upon infection, a myriad of virulence proteins (effectors encoded by A/E pathogens are injected through their conserved type III secretion systems (T3SS into host cells where they interfere with cell signaling cascades, in particular the nuclear factor kappaB (NF-κB signaling pathway that orchestrates both innate and adaptive immune responses for host defense. Among the T3SS-secreted non-LEE-encoded (Nle effectors, NleC, a metalloprotease, has been recently elucidated to modulate host NF-κB signaling by cleaving NF-κB Rel subunits. However, it remains elusive how NleC recognizes NF-κB Rel subunits and how the NleC-mediated cleavage impacts on host immune responses in infected cells and animals. In this study, we show that NleC specifically targets p65/RelA through an interaction with a unique N-terminal sequence in p65. NleC cleaves p65 in intestinal epithelial cells, albeit a small percentage of the molecule, to generate the p65¹⁻³⁸ fragment during C. rodentium infection in cultured cells. Moreover, the NleC-mediated p65 cleavage substantially affects the expression of a subset of NF-κB target genes encoding proinflammatory cytokines/chemokines, immune cell infiltration in the colon, and tissue injury in C. rodentium-infected mice. Mechanistically, the NleC cleavage-generated p65¹⁻³⁸ fragment interferes with the interaction between p65 and ribosomal protein S3 (RPS3, a 'specifier' subunit of NF-κB that confers a subset of proinflammatory gene transcription, which amplifies the effect of cleaving only a small percentage of p65 to modulate NF-κB-mediated gene expression. Thus, our results reveal a novel mechanism for A/E pathogens to specifically block NF-κB signaling and inflammatory responses by cleaving a

  13. Bacillus cereus AR156 primes induced systemic resistance by suppressing miR825/825* and activating defense-related genes in Arabidopsis.

    Science.gov (United States)

    Niu, Dongdong; Xia, Jing; Jiang, Chunhao; Qi, Beibei; Ling, Xiaoyu; Lin, Siyuan; Zhang, Weixiong; Guo, Jianhua; Jin, Hailing; Zhao, Hongwei

    2016-04-01

    Small RNAs play an important role in plant immune responses. However, their regulatory function in induced systemic resistance (ISR) is nascent. Bacillus cereus AR156 is a plant growth-promoting rhizobacterium that induces ISR in Arabidopsis against bacterial infection. Here, by comparing small RNA profiles of Pseudomonas syringae pv. tomato (Pst) DC3000-infected Arabidopsis with and without AR156 pretreatment, we identified a group of Arabidopsis microRNAs (miRNAs) that are differentially regulated by AR156 pretreatment. miR825 and miR825* are two miRNA generated from a single miRNA gene. Northern blot analysis indicated that they were significantly downregulated in Pst DC3000-infected plants pretreated with AR156, in contrast to the plants without AR156 pretreatment. miR825 targets two ubiquitin-protein ligases, while miR825* targets toll-interleukin-like receptor (TIR)-nucleotide binding site (NBS) and leucine-rich repeat (LRR) type resistance (R) genes. The expression of these target genes negatively correlated with the expression of miR825 and miR825*. Moreover, transgenic plants showing reduced expression of miR825 and miR825* displayed enhanced resistance to Pst DC3000 infection, whereas transgenic plants overexpressing miR825 and miR825* were more susceptible. Taken together, our data indicates that Bacillus cereus AR156 pretreatment primes ISR to Pst infection by suppressing miR825 and miR825* and activating the defense related genes they targeted. © 2015 Institute of Botany, Chinese Academy of Sciences.

  14. Silicon-enhanced resistance to cadmium toxicity in Brassica chinensis L. is attributed to Si-suppressed cadmium uptake and transport and Si-enhanced antioxidant defense capacity

    Energy Technology Data Exchange (ETDEWEB)

    Song Alin [College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Li Zhaojun [Ministry of Agriculture Key Laboratory of Crop Nutrition and Fertilization, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing 100081 (China); Zhang Jie [College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Xue Gaofeng; Fan Fenliang [Ministry of Agriculture Key Laboratory of Crop Nutrition and Fertilization, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing 100081 (China); Liang Yongchao, E-mail: ycliang@caas.ac.cn [College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Ministry of Agriculture Key Laboratory of Crop Nutrition and Fertilization, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing 100081 (China); Key Laboratory of Oasis Eco-Agriculture, College of Agriculture, Shihezi University, Shihezi 832003 (China)

    2009-12-15

    A series of hydroponics experiments were performed to investigate roles of silicon (Si) in enhancing cadmium (Cd) tolerance in two pakchoi (Brassica chinensis L.) cultivars: i.e. cv. Shanghaiqing, a Cd-sensitive cultivar, and cv. Hangyoudong, a Cd-tolerant cultivar. Plants were grown under 0.5 and 5 mg Cd L{sup -1} Cd stress without or with 1.5 mM Si. Plant growth of the Cd-tolerant cultivar was stimulated at the lower Cd level, but was decreased at the higher Cd level when plants were treated with Cd for one week. However, Plant growth was severely inhibited at both Cd levels as stress duration lasted for up to three weeks. Plant growth of the Cd-sensitive cultivar was severely inhibited at both Cd levels irrespective of Cd stress duration. Addition of Si increased shoot and root biomass of both cultivars at both Cd levels and decreased Cd uptake and root-to-shoot transport. Superoxide dismutase, catalase and ascorbate peroxidase activities decreased, but malondialdehyde and H{sub 2}O{sub 2} concentrations increased at the higher Cd level, which were counteracted by Si added. Ascorbic acid, glutathione and non-protein thiols concentrations increased at the higher Cd level, which were further intensified by addition of Si. The effects of Si and Cd on the antioxidant enzyme activity were further verified by isoenzyme analysis. Silicon was more effective in enhancing Cd tolerance in the Cd-tolerant cultivar than in the Cd-sensitive cultivar. It can be concluded that Si-enhanced Cd tolerance in B. chinensis is attributed mainly to Si-suppressed Cd uptake and root-to-shoot Cd transport and Si-enhanced antioxidant defense activity.

  15. Caspase-1 dependent IL-1β secretion is critical for host defense in a mouse model of Chlamydia pneumoniae lung infection.

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    Kenichi Shimada

    Full Text Available Chlamydia pneumoniae (CP is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the 'inflammasome', and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1⁻/⁻ mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1⁻/⁻ mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice phenocopies Caspase-1-deficient mice, and administration of recombinant IL-1β rescues CP infected Caspase-1⁻/⁻ mice from mortality, indicating that IL-1β secretion is crucial for host immune defense against CP lung infection. In vitro investigation reveals that CP-induced IL-1β secretion by macrophages requires TLR2/MyD88 and NLRP3/ASC/Caspase-1 signaling. Entry into the cell by CP and new protein synthesis by CP are required for inflammasome activation. Neither ROS nor cathepsin was required for CP infection induced inflammasome activation. Interestingly, Caspase-1 activation during CP infection occurs with mitochondrial dysfunction indicating a possible mechanism involving the mitochondria for CP-induced inflammasome activation.

  16. Molecular insights into a molluscan transferrin homolog identified from disk abalone (Haliotis discus discus) evidencing its detectable role in host antibacterial defense.

    Science.gov (United States)

    Herath, H M L P B; Elvitigala, Don Anushka Sandaruwan; Godahewa, G I; Whang, Ilson; Lee, Jehee

    2015-11-01

    The basic function of transferrin is to bind iron (III) ions in the medium and to deliver them to the locations where they are required for metabolic processes. It also takes part in the host immune defense mainly via its ability to bind to iron (III) ions. Hence, transferrin is also identified as an important acute-phase protein in host immunity. Abalones are major shellfish aquaculture crops that are susceptible to a range of marine microbial infections. Since transferrin is known to be a major player in innate immunity, in the present study we sought to identify, and molecularly and functionally characterize a transferrin-like gene from disk abalone (Haliotis discus discus) named as AbTrf. AbTrf consisted of a 2187-bp open reading frame (ORF) which encodes a 728 amino acid (aa) protein. The putative amino acid sequence of AbTrf harbored N- and C-terminal transferrin-like domains, active sites for iron binding, and conserved cysteine residues. A constitutive tissue specific AbTrf expression pattern was detected by qPCR in abalones where mantle and muscle showed high AbTrf expression levels. Three immune challenge experiments were conducted using Vibrio parahaemolyticus, Listeria monocytogenes and LPS as stimuli and, subsequently, AbTrf mRNA expression levels were quantified in gill and hemocytes in a time-course manner. The mRNA expression was greatly induced in both tissues in response to both challenges. Evidencing the functional property of transferrins, recombinant AbTrf N-terminal domain (AbTrf-N) showed dose-dependent iron (III) binding activity detected by chrome azurol S (CAS) assay system. Moreover, recombinant AbTrf-N could significantly inhibit the growth of iron-dependent bacterium, Escherichia coli in a dose-dependent manner. However, AbTrf-N was unable to show any detectable bacteriostatic activity against iron-independent bacterium Lactobacillus plantarum (L. plantarum) even at its highest concentration. Collectively, our results suggest that Ab

  17. Infection with host-range mutant adenovirus 5 suppresses innate immunity and induces systemic CD4+ T cell activation in rhesus macaques.

    Science.gov (United States)

    Qureshi, Huma; Genescà, Meritxell; Fritts, Linda; McChesney, Michael B; Robert-Guroff, Marjorie; Miller, Christopher J

    2014-01-01

    Ad5 is a common cause of respiratory disease and an occasional cause of gastroenteritis and conjunctivitis, and seroconversion before adolescence is common in humans. To gain some insight into how Ad5 infection affects the immune system of rhesus macaques (RM) 18 RM were infected with a host-range mutant Ad5 (Ad5hr) by 3 mucosal inoculations. There was a delay of 2 to 6 weeks after the first inoculation before plasmacytoid dendritic cell (pDC) frequency and function increased in peripheral blood. Primary Ad5hr infection suppressed IFN-γ mRNA expression, but the second Ad5hr exposure induced a rapid increase in IFN-gamma mRNA in peripheral blood mononuclear cells (PBMC). Primary Ad5hr infection suppressed CCL20, TNF and IL-1 mRNA expression in PBMC, and subsequent virus exposures further dampened expression of these pro-inflammatory cytokines. Primary, but not secondary, Ad5hr inoculation increased the frequency of CXCR3+ CD4+ T cells in blood, while secondary, but not primary, Ad5hr infection transiently increased the frequencies of Ki67+, HLADR+ and CD95+/CCR5+ CD4+ T cells in blood. Ad5hr infection induced polyfunctional CD4 and CD8+ T cells specific for the Ad5 hexon protein in all of the animals. Thus, infection with Ad5hr induced a complex pattern of innate and adaptive immunity in RM that included transient systemic CD4+ T cell activation and suppressed innate immunity on re-exposure to the virus. The complex effects of adenovirus infection on the immune system may help to explain the unexpected results of testing Ad5 vector expressing HIV antigens in Ad5 seropositive people.

  18. Feline Panleucopenia Virus NS2 Suppresses the Host IFN-β Induction by Disrupting the Interaction between TBK1 and STING

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    Hongtao Kang

    2017-01-01

    Full Text Available Feline panleucopenia virus (FPV is a highly infectious pathogen that causes severe diseases in pets, economically important animals and wildlife in China. Although FPV was identified several years ago, little is known about how it overcomes the host innate immunity. In the present study, we demonstrated that infection with the FPV strain Philips-Roxane failed to activate the interferon β (IFN-β pathway but could antagonize the induction of IFN stimulated by Sendai virus (SeV in F81 cells. Subsequently, by screening FPV nonstructural and structural proteins, we found that only nonstructural protein 2 (NS2 significantly suppressed IFN expression. We demonstrated that the inhibition of SeV-induced IFN-β production by FPV NS2 depended on the obstruction of the IFN regulatory factor 3 (IRF3 signaling pathway. Further, we verified that NS2 was able to target the serine/threonine-protein kinase TBK1 and prevent it from being recruited by stimulator of interferon genes (STING protein, which disrupted the phosphorylation of the downstream protein IRF3. Finally, we identified that the C-terminus plus the coiled coil domain are the key domains of NS2 that are required for inhibiting the IFN pathway. Our study has yielded strong evidence for the FPV mechanisms that counteract the host innate immunity.

  19. Label-free Proteomic Reveals that Cowpea Severe Mosaic Virus Transiently Suppresses the Host Leaf Protein Accumulation During the Compatible Interaction with Cowpea (Vigna unguiculata [L.] Walp.).

    Science.gov (United States)

    Paiva, Ana L S; Oliveira, Jose T A; de Souza, Gustavo A; Vasconcelos, Ilka M

    2016-12-02

    Viruses are important plant pathogens that threaten diverse crops worldwide. Diseases caused by Cowpea severe mosaic virus (CPSMV) have drawn attention because of the serious damages they cause to economically important crops including cowpea. This work was undertaken to quantify and identify the responsive proteins of a susceptible cowpea genotype infected with CPSMV, in comparison with mock-inoculated controls, using label-free quantitative proteomics and databanks, aiming at providing insights on the molecular basis of this compatible interaction. Cowpea leaves were mock- or CPSMV-inoculated and 2 and 6 days later proteins were extracted and analyzed. More than 3000 proteins were identified (data available via ProteomeXchange, identifier PXD005025) and 75 and 55 of them differentially accumulated in response to CPSMV, at 2 and 6 DAI, respectively. At 2 DAI, 76% of the proteins decreased in amount and 24% increased. However, at 6 DAI, 100% of the identified proteins increased. Thus, CPSMV transiently suppresses the synthesis of proteins involved particularly in the redox homeostasis, protein synthesis, defense, stress, RNA/DNA metabolism, signaling, and other functions, allowing viral invasion and spread in cowpea tissues.

  20. The Importance of the KR-Rich Region of the Coat Protein of Ourmia melon virus for Host Specificity, Tissue Tropism, and Interference With Antiviral Defense.

    Science.gov (United States)

    Rossi, Marika; Vallino, Marta; Abbà, Simona; Ciuffo, Marina; Balestrini, Raffaella; Genre, Andrea; Turina, Massimo

    2015-01-01

    The N-terminal region of the Ourmia melon virus (OuMV) coat protein (CP) contains a short lysine/arginine-rich (KR) region. By alanine scanning mutagenesis, we showed that the KR region influences pathogenicity and virulence of OuMV without altering viral particle assembly. A mutant, called OuMV6710, with three basic residue substitutions in the KR region, was impaired in the ability to maintain the initial systemic infection in Nicotiana benthamiana and to infect both cucumber and melon plants systemically. The integrity of this protein region was also crucial for encapsidation of viral genomic RNA; in fact, certain mutations within the KR region partially compromised the RNA encapsidation efficiency of the CP. In Arabidopsis thaliana Col-0, OuMV6710 was impaired in particle accumulation; however, this phenotype was abolished in dcl2/dcl4 and dcl2/dcl3/dcl4 Arabidopsis mutants defective for antiviral silencing. Moreover, in contrast to CPwt, in situ immunolocalization experiments indicated that CP6710 accumulates efficiently in the spongy mesophyll tissue of infected N. benthamiana and A. thaliana leaves but only occasionally infects palisade tissues. These results provided strong evidence of a crucial role for OuMV CP during viral infection and highlighted the relevance of the KR region in determining tissue tropism, host range, pathogenicity, and RNA affinity, which may be all correlated with a possible CP silencing-suppression activity.

  1. Plant innate immunity induced by flagellin suppresses the hypersensitive response in non-host plants elicited by Pseudomonas syringae pv. averrhoi.

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    Chia-Fong Wei

    Full Text Available A new pathogen, Pseudomonas syringae pv. averrhoi (Pav, which causes bacterial spot disease on carambola was identified in Taiwan in 1997. Many strains of this pathovar have been isolated from different locations and several varieties of hosts. Some of these strains, such as HL1, are nonmotile and elicit a strong hypersensitive response (HR in nonhost tobacco leaves, while other strains, such as PA5, are motile and elicit a weak HR. Based on the image from a transmission electron microscope, the results showed that HL1 is flagellum-deficient and PA5 has normal flagella. Here we cloned and analyzed the fliC gene and glycosylation island from Pav HL1 and PA5. The amino acid sequences of FliC from HL1 and PA5 are identical to P. s. pvs. tabaci (Pta, glycinea and phaseolicola and share very high similarity with other pathovars of P. syringae. In contrast to the flagellin mutant PtaΔfliC, PA5ΔfliC grows as well as wild type in the host plant, but it elicits stronger HR than wild type does in non-host plants. Furthermore, the purified Pav flagellin, but not the divergent flagellin from Agrobacterium tumefaciens, is able to impair the HR induced by PA5ΔfliC. PA5Δfgt1 possessing nonglycosylated flagella behaved as its wild type in both bacterial growth in host and HR elicitation. Flagellin was infiltrated into tobacco leaves either simultaneously with flagellum-deficient HL1 or prior to the inoculation of wild type HL1, and both treatments impaired the HR induced by HL1. Moreover, the HR elicited by PA5 and PA5ΔfliC was enhanced by the addition of cycloheximide, suggesting that the flagellin is one of the PAMPs (pathogen-associated molecular patterns contributed to induce the PAMP-triggered immunity (PTI. Taken together, the results shown in this study reveal that flagellin in Pav is capable of suppressing HR via PTI induction during an incompatible interaction.

  2. Identification and characterization of molluscan caveolin-1 ortholog from Haliotis discus discus: Possible involvement in embryogenesis and host defense mechanism against pathogenic stress.

    Science.gov (United States)

    Udayantha, H M V; Bathige, S D N K; Priyathilaka, Thanthrige Thiunuwan; Lee, Sukkyoung; Kim, Myoung-Jin; Lee, Jehee

    2018-01-01

    Caveolins are principal membrane proteins of caveolae that play a central role in signal transduction, substrate transport, and membrane trafficking in various cell types. Numerous studies have reported the crucial role of caveolin-1 (CAV1) in response to invading microbes; yet, very little is known about molluscan CAV1. In this study, we identified and characterized CAV1 ortholog from the disk abalone, Haliotis discus discus (HdCAV1). The cDNA sequence of HdCAV1 is 826 bp long and encodes a 127-amino acid polypeptide. Characteristic caveolin superfamily domain (Glu 3 - Lys 126 ) and two possible transmembrane domains (Cys 48 - Tyr 67 and Ile 103 - Phe 120 ) were identified in the HdCAV1 protein. Homology analysis revealed that HdCAV1 shared higher identity (>47%) with molluscans, but lower identity with other species. Phylogenetic tree constructed by the neighbor-joining (NJ) method revealed a distinct evolutionary pathway for molluscans. Transcriptional analysis by SYBR Green qPCR showed the highest expression of HdCAV1 mRNA in late veliger stage, as compared to that in other embryonic developmental stages of disk abalone. In adult animals, gill tissue showed highest HdCAV1 transcript levels under normal physiological condition. Stimulations with two bacteria (Vibrio parahaemolyticus and Listeria monocytogenes), viral hemorrhagic septicemia virus, and two pathogen-associated molecular patterns (LPS and poly I:C) significantly modulated the expression of HdCAV1 transcripts. Collectively, these data suggest that CAV1 plays an important role in embryogenesis and host immune defense in disk abalone. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Lactobacillus reuteri I5007 Modulates Intestinal Host Defense Peptide Expression in the Model of IPEC-J2 Cells and Neonatal Piglets

    Science.gov (United States)

    Liu, Hongbin; Hou, Chengli; Wang, Gang; Jia, Hongmin; Yu, Haitao; Zeng, Xiangfang; Thacker, Philip A.; Zhang, Guolong; Qiao, Shiyan

    2017-01-01

    Modulation of the synthesis of endogenous host defense peptides (HDPs) by probiotics represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections in human and animals. However, the extent of HDP modulation by probiotics is species dependent and strain specific. In the present study, The porcine small intestinal epithelial cell line (IPEC-J2) cells and neonatal piglets were used as in-vitro and in-vivo models to test whether Lactobacillus reuteri I5007 could modulate intestinal HDP expression. Gene expressions of HDPs, toll-like receptors, and fatty acid receptors were determined, as well as colonic short chain fatty acid concentrations and microbiota. Exposure to 108 colony forming units (CFU)/mL of L. reuteri I5007 for 6 h significantly increased the expression of porcine β-Defensin2 (PBD2), pBD3, pBD114, pBD129, and protegrins (PG) 1-5 in IPEC-J2 cells. Similarly, L. reuteri I5007 administration significantly increased the expression of jejunal pBD2 as well as colonic pBD2, pBD3, pBD114, and pBD129 in neonatal piglets (p reuteri I5007 in the piglets did not affect the colonic microbiota structure. Our findings suggested that L. reuteri I5007 could modulate intestinal HDP expression and improve the gut health of neonatal piglets, probably through the increase in colonic butyric acid concentration and the up-regulation of the downstream molecules of butyric acid, PPAR-γ and GPR41, but not through modifying gut microbiota structure. PMID:28561758

  4. Lactobacillus reuteri I5007 Modulates Intestinal Host Defense Peptide Expression in the Model of IPEC-J2 Cells and Neonatal Piglets.

    Science.gov (United States)

    Liu, Hongbin; Hou, Chengli; Wang, Gang; Jia, Hongmin; Yu, Haitao; Zeng, Xiangfang; Thacker, Philip A; Zhang, Guolong; Qiao, Shiyan

    2017-05-31

    Modulation of the synthesis of endogenous host defense peptides (HDPs) by probiotics represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections in human and animals. However, the extent of HDP modulation by probiotics is species dependent and strain specific. In the present study, The porcine small intestinal epithelial cell line (IPEC-J2) cells and neonatal piglets were used as in-vitro and in-vivo models to test whether Lactobacillus reuteri I5007 could modulate intestinal HDP expression. Gene expressions of HDPs, toll-like receptors, and fatty acid receptors were determined, as well as colonic short chain fatty acid concentrations and microbiota. Exposure to 10⁸ colony forming units (CFU)/mL of L. reuteri I5007 for 6 h significantly increased the expression of porcine β-Defensin2 (PBD2), pBD3, pBD114, pBD129, and protegrins (PG) 1-5 in IPEC-J2 cells. Similarly, L. reuteri I5007 administration significantly increased the expression of jejunal pBD2 as well as colonic pBD2, pBD3, pBD114, and pBD129 in neonatal piglets ( p L. reuteri I5007 in the piglets did not affect the colonic microbiota structure. Our findings suggested that L. reuteri I5007 could modulate intestinal HDP expression and improve the gut health of neonatal piglets, probably through the increase in colonic butyric acid concentration and the up-regulation of the downstream molecules of butyric acid, PPAR-γ and GPR41, but not through modifying gut microbiota structure.

  5. Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents.

    Science.gov (United States)

    Conlon, J Michael; Mechkarska, Milena; Lukic, Miodrag L; Flatt, Peter R

    2014-07-01

    Frog skin constitutes a rich source of peptides with a wide range of biological properties. These include host-defense peptides with cytotoxic activities against bacteria, fungi, protozoa, viruses, and mammalian cells. Several hundred such peptides from diverse species have been described. Although attention has been focused mainly on antimicrobial activity, the therapeutic potential of frog skin peptides as anti-infective agents remains to be realized and no compound based upon their structures has yet been adopted in clinical practice. Consequently, alternative applications are being explored. Certain naturally occurring frog skin peptides, and analogs with improved therapeutic properties, show selective cytotoxicity against tumor cells and viruses and so have potential for development into anti-cancer and anti-viral agents. Some peptides display complex cytokine-mediated immunomodulatory properties. Effects on the production of both pro-inflammatory and anti-inflammatory cytokines by peritoneal macrophages and peripheral blood mononuclear cells have been observed so that clinical applications as anti-inflammatory, immunosuppressive, and immunostimulatory agents are possible. Several frog skin peptides, first identified on the basis of antimicrobial activity, have been shown to stimulate insulin release both in vitro and in vivo and so show potential as incretin-based therapies for treatment of patients with Type 2 diabetes mellitus. This review assesses the therapeutic possibilities of peptides from frogs belonging to the Ascaphidae, Alytidae, Pipidae, Dicroglossidae, Leptodactylidae, Hylidae, and Ranidae families that complement their potential role as anti-infectives for use against multidrug-resistant microorganisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Microbial Pathogenesis and Host Defense.

    Science.gov (United States)

    1998-03-01

    The bvrS-bvrR system showed high homology with the chvl-chvG two-component regulatory system described for Agrobacterium . tumefaciens (a plant...systems in other pathogens include the virB operon in Agrobacterium and the ptl operon in Bordetella. 13 GENETIC ANALYSIS OF MOUSE SUSCEPTIBILITY TO...address these questions, our lab employs the interaction between the crucifer Arabidopis thaliana and Pseudomonas syringae pv. tomato , the causitive agent

  7. Lactobacillus reuteri I5007 Modulates Intestinal Host Defense Peptide Expression in the Model of IPEC-J2 Cells and Neonatal Piglets

    Directory of Open Access Journals (Sweden)

    Hongbin Liu

    2017-05-01

    Full Text Available Modulation of the synthesis of endogenous host defense peptides (HDPs by probiotics represents a novel antimicrobial approach for disease control and prevention, particularly against antibiotic-resistant infections in human and animals. However, the extent of HDP modulation by probiotics is species dependent and strain specific. In the present study, The porcine small intestinal epithelial cell line (IPEC-J2 cells and neonatal piglets were used as in-vitro and in-vivo models to test whether Lactobacillus reuteri I5007 could modulate intestinal HDP expression. Gene expressions of HDPs, toll-like receptors, and fatty acid receptors were determined, as well as colonic short chain fatty acid concentrations and microbiota. Exposure to 108 colony forming units (CFU/mL of L. reuteri I5007 for 6 h significantly increased the expression of porcine β-Defensin2 (PBD2, pBD3, pBD114, pBD129, and protegrins (PG 1-5 in IPEC-J2 cells. Similarly, L. reuteri I5007 administration significantly increased the expression of jejunal pBD2 as well as colonic pBD2, pBD3, pBD114, and pBD129 in neonatal piglets (p < 0.05. This was probably associated with the increase in colonic butyric acid concentration and up-regulating expression of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ and G Protein-Coupled Receptor 41 (GPR41 (p < 0.05, but not with stimulation of Pattern-Recognition Receptors. Additionally, supplementation with L. reuteri I5007 in the piglets did not affect the colonic microbiota structure. Our findings suggested that L. reuteri I5007 could modulate intestinal HDP expression and improve the gut health of neonatal piglets, probably through the increase in colonic butyric acid concentration and the up-regulation of the downstream molecules of butyric acid, PPAR-γ and GPR41, but not through modifying gut microbiota structure.

  8. The Effect of Water Limitation on Volatile Emission, Tree Defense Response, and Brood Success of Dendroctonus ponderosae in Two Pine Hosts, Lodgepole, and Jack Pine

    OpenAIRE

    Lusebrink, Inka; Erbilgin, Nadir; Evenden, Maya L.

    2016-01-01

    The mountain pine beetle (MPB; Dendroctonus ponderosae) has recently expanded its range from lodgepole pine forest into the lodgepole × jack pine hybrid zone in central Alberta, within which it has attacked pure jack pine. This study tested the effects of water limitation on tree defense response of mature lodgepole and jack pine (Pinus contorta and Pinus banksiana) trees in the field. Tree defense response was initiated by inoculation of trees with the MPB-associated fungus Grosmannia clavig...

  9. Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes

    Directory of Open Access Journals (Sweden)

    Killick Kate E

    2011-12-01

    study demonstrates that genome-wide transcriptional profiling of PBL can distinguish active M. bovis-infected animals from control non-infected animals. Furthermore, the results obtained support previous investigations demonstrating that mycobacterial infection is associated with host transcriptional suppression. These data support the use of transcriptomic technologies to enable the identification of robust, reliable transcriptional markers of active M. bovis infection.

  10. Indirect plant defense against insect herbivores: a review.

    Science.gov (United States)

    Aljbory, Zainab; Chen, Ming-Shun

    2018-02-01

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

  11. TGF-β-Induced CD8+CD103+Regulatory T Cells Show Potent Therapeutic Effect on Chronic Graft-versus-Host Disease Lupus by Suppressing B Cells.

    Science.gov (United States)

    Zhong, Haowen; Liu, Ya; Xu, Zhenjian; Liang, Peifeng; Yang, Hui; Zhang, Xiao; Zhao, Jun; Chen, Junzhen; Fu, Sha; Tang, Ying; Lv, Jun; Wang, Julie; Olsen, Nancy; Xu, Anping; Zheng, Song Guo

    2018-01-01

    Lupus nephritis is one of most severe complications of systemic erythematosus lupus and current approaches are not curative for lupus nephritis. Although CD4 + Foxp3 + regulatory T cells (Treg) are crucial for prevention of autoimmunity, the therapeutic effect of these cells on lupus nephritis is not satisfactory. We previously reported that CD8 + CD103 + Treg induced ex vivo with TGF-β1 and IL-2 (CD8 + CD103 + iTreg), regardless of Foxp3 expression, displayed potent immunosuppressive effect on Th cell response and had therapeutic effect on Th cell-mediated colitis. Here, we tested whether CD8 + CD103 + iTreg can ameliorate lupus nephritis and determined potential molecular mechanisms. Adoptive transfer of CD8 + CD103 + iTreg but not control cells to chronic graft-versus-host disease with a typical lupus syndrome showed decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, lowered renal deposition of IgG/C3, and improved survival. CD8 + CD103 + iTreg cells suppressed not only T helper cells but also B cell responses directly that may involve in both TGF-β and IL-10 signals. Using RNA-seq, we demonstrated CD8 + CD103 + iTreg have its own unique expression profiles of transcription factors. Thus, current study has identified and extended the target cells of CD8 + CD103 + iTreg and provided a possible application of this new iTreg subset on lupus nephritis and other autoimmune diseases.

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

    Science.gov (United States)

    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

  13. An Arabidopsis lipid flippase is required for timely recruitment of defenses to the host-pathogen interface at the plant cell surface

    Science.gov (United States)

    Deposition of cell wall-reinforcing papillae is an integral component of the plant immune response. The Arabidopsis PENETRATION 3 (PEN3) ATP binding cassette (ABC) transporter plays a role in defense against numerous pathogens and is recruited to sites of pathogen detection where it accumulates with...

  14. Genetic variation of lodgepole pine physical and chemical defenses associated with each step in host selection behavior sequence by mountain pine beetle

    Science.gov (United States)

    Kimberly F. Wallin; Daniel S. Ott; Alvin D. Yanchuk

    2012-01-01

    Abiotic and biotic stressors exert selective pressures on plants, and over evolutionary time lead to the development of specialized adaptations and specific responses to stresses (Safranyik and Carroll 2006, Wallin and Raffa 2002). In this way, the environment in which plants evolve shapes their life cycles, range, growth, reproduction, and defenses. Insects and...

  15. Melon Fly, (Diptera: Tephritidae, Infestation in Host Fruits in the Southwestern Islands of Japan before the Initiation of Island-wide Population Suppression, as Recorded in Publications of Japanese Public Institutions

    Directory of Open Access Journals (Sweden)

    Grant T. Mcquate

    2015-01-01

    Full Text Available Bactrocera cucurbitae (Coquillett is a tephritid fruit fly native to the Indo-Malayan region. Its distribution, though, has extended to include Africa, temperate Asia, and a number of Pacific islands. It became established in Japan in 1919 in the Yaeyama Islands and spread north in the Southwestern Islands of Japan. It was subsequently eradicated from these islands by an eradication program that extended from 1972 to 1993. As part of an effort to develop a worldwide database on the status of fruits as hosts of melon fly, the infestation data gathered from host fruits collected in this eradication program, before the initiation of suppression activities, are summarized here. Bactrocera cucurbitae infestation was documented in 24 plant taxa of four plant families (Caricaceae, Cucurbitaceae, Moraceae, and Solanaceae, with the following four new hosts identified: Ficus erecta Thunb., F. pumila L. (Moraceae, Solanum erianthum D. Don (Solanaceae, and Zehneria liukiuensis Jeffrey ex Walker (Cucurbitaceae.

  16. Dynamic defense workshop :

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, Sean Michael; Doak, Justin E.; Haas, Jason Juedes.; Helinski, Ryan; Lamb, Christopher C.

    2013-02-01

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

  17. Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection

    DEFF Research Database (Denmark)

    Steinstraesser, Lars; Hirsch, Tobias; Schulte, Matthias

    2012-01-01

    Innate defense regulators (IDRs) are synthetic immunomodulatory versions of natural host defense peptides (HDP). IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy....... Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR....... It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018....

  18. Broadly conserved fungal effector BEC1019 suppresses host cell death and enhances pathogen virulence in powdery mildew of barley (Hordeum vulgare L.)

    Science.gov (United States)

    The interaction of barley, Hordeum vulgare L., with the biotrophic powdery mildew fungus, Blumeria graminis f. sp. hordei, is an ideal model to address fundamental questions in host resistance and susceptibility. Effector proteins secreted by B. graminis act to inhibit, induce, or accelerate host pr...

  19. Evidence for suppression of immunity as a driver for genomic introgressions and host range expansion in races of Albugo candida, a generalist parasite

    DEFF Research Database (Denmark)

    McMullan, Mark; Gardiner, Anastasia; Bailey, Kate

    2015-01-01

    How generalist parasites with wide host ranges can evolve is a central question in parasite evolution. Albugo candida is an obligate biotrophic parasite that consists of many physiological races that each specialize on distinct Brassicaceae host species. By analyzing genome sequence assemblies of......, Darwin's finches, sunflowers and cichlid fishes, and the implications of introgression for pathogen evolution in an agro-ecological environment....

  20. SlCNGC1 and SlCNGC14 Suppress Xanthomonas oryzae pv. oryzicola-Induced Hypersensitive Response and Non-host Resistance in Tomato

    Directory of Open Access Journals (Sweden)

    Xuan-Rui Zhang

    2018-03-01

    Full Text Available Mechanisms underlying plant non-host resistance to Xanthomonas oryzae pv. oryzicola (Xoc, the pathogen causing rice leaf streak disease, are largely unknown. Cyclic nucleotide-gated ion channels (CNGCs are calcium-permeable channels that are involved in various biological processes including plant resistance. In this study, functions of two tomato CNGC genes SlCNGC1 and SlCNGC14 in non-host resistance to Xoc were analyzed. Silencing of SlCNGC1 and SlCNGC14 in tomato significantly enhanced Xoc-induced hypersensitive response (HR and non-host resistance, demonstrating that both SlCNGC1 and SlCNGC14 negatively regulate non-host resistance related HR and non-host resistance to Xoc in tomato. Silencing of SlCNGC1 and SlCNGC14 strikingly increased Xoc-induced callose deposition and strongly promoted both Xoc-induced and flg22-elicited H2O2, indicating that these two SlCNGCs repress callose deposition and ROS accumulation to attenuate non-host resistance and PAMP-triggered immunity (PTI. Importantly, silencing of SlCNGC1 and SlCNGC14 apparently compromised cytosolic Ca2+ accumulation, implying that SlCNGC1 and SlCNGC14 function as Ca2+ channels and negatively regulate non-host resistance and PTI-related responses through modulating cytosolic Ca2+ accumulation. SlCNGC14 seemed to play a stronger regulatory role in the non-host resistance and PTI compared to SlCNGC1. Our results reveal the contribution of CNGCs and probably also Ca2+ signaling pathway to non-host resistance and PTI.

  1. Cooperative Immune Suppression by Escherichia coli and Shigella Effector Proteins.

    Science.gov (United States)

    de Jong, Maarten F; Alto, Neal M

    2018-04-01

    The enteric attaching and effacing (A/E) pathogens enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) and the invasive pathogens enteroinvasive E. coli (EIEC) and Shigella encode type III secretion systems (T3SS) used to inject effector proteins into human host cells during infection. Among these are a group of effectors required for NF-κB-mediated host immune evasion. Recent studies have identified several effector proteins from A/E pathogens and EIEC/ Shigella that are involved in suppression of NF-κB and have uncovered their cellular and molecular functions. A novel mechanism among these effectors from both groups of pathogens is to coordinate effector function during infection. This cooperativity among effector proteins explains how bacterial pathogens are able to effectively suppress innate immune defense mechanisms in response to diverse classes of immune receptor signaling complexes (RSCs) stimulated during infection. Copyright © 2018 American Society for Microbiology.

  2. IL-17A and Th17 Cells in Lung Inflammation: An Update on the Role of Th17 Cell Differentiation and IL-17R Signaling in Host Defense against Infection

    Directory of Open Access Journals (Sweden)

    Hsing-Chuan Tsai

    2013-01-01

    Full Text Available The significance of Th17 cells and interleukin- (IL-17A signaling in host defense and disease development has been demonstrated in various infection and autoimmune models. Numerous studies have indicated that Th17 cells and its signature cytokine IL-17A are critical to the airway’s immune response against various bacteria and fungal infection. Cytokines such as IL-23, which are involved in Th17 differentiation, play a critical role in controlling Klebsiella pneumonia (K. pneumonia infection. IL-17A acts on nonimmune cells in infected tissues to strengthen innate immunity by inducing the expression of antimicrobial proteins, cytokines, and chemokines. Mice deficient in IL-17 receptor (IL-17R expression are susceptible to infection by various pathogens. In this review, we summarize the recent advances in unraveling the mechanism behind Th17 cell differentiation, IL-17A/IL-17R signaling, and also the importance of IL-17A in pulmonary infection.

  3. The ectoparasitic wasp Eulophus pennicornis (Hymenoptera: Eulophidae) uses instar-specific endocrine disruption strategies to suppress the development of its host Lacanobia oleracea (Lepidoptera: Noctuidae).

    Science.gov (United States)

    Edwards, John P; Bell, Howard A; Audsley, Neil; Marris, Gay C; Kirkbride-Smith, Anne; Bryning, Gareth; Frisco, Caroline; Cusson, Michel

    2006-01-01

    To successfully complete its development, the gregarious ectoparasitoid Eulophus pennicornis must inhibit the moult of its host, Lacanobia oleracea. In the present study, we examined the possibility that moult- and metamorphosis-associated endocrine events may be disrupted in caterpillars parasitized as newly moulted last (sixth) instars. Juvenile hormone (JH) titres on days 2 and 5 of the final stadium were significantly higher (> 100 fold) in parasitized than in non-parasitized hosts, in which JH was essentially absent. Elevated JH levels were associated with reduced haemolymph JH esterase (JHE) activity (down by 99.8%) and enhanced in vitro JH biosynthesis by the corpora allata (CA) (up to 4.5 fold). Wasp adults and/or larvae, in which we measured high levels of JH III (up to 2.7 ng/g), but little or no JH I or JH II, were not seen as likely sources of JH in parasitized hosts, in which we found mostly JH I and JH II. In addition, removal of parasitoid eggs or larvae after oviposition did not prevent the rise in JH titres seen in parasitoid-laden hosts, suggesting that wasp venom may be responsible for the observed hormonal dysfunction. Host haemolymph 20-hydroxyecdysone (20-E) levels were largely unaffected by parasitism during the final stadium although they were observed to increase earlier and decrease more rapidly in parasitized insects. We compare these results with those reported earlier for L. oleracea larvae parasitized by E. pennicornis as penultimate (fifth) instars, which display significantly depressed 20-E titres relative to control larvae. We conclude that E. pennicornis employs host endocrine-disruption strategies that differ according to whether the host is parasitized as a penultimate or final-stadium larva.

  4. Transforming Defense

    National Research Council Canada - National Science Library

    Lamb, Christopher J; Bunn, M. E; Lutes, Charles; Cavoli, Christopher

    2005-01-01

    .... Despite the resources and attention consumed by the war on terror, and recent decisions by the White House to curtail the growth of defense spending, the senior leadership of the Department of Defense (DoD...

  5. Plant Defense against Insect Herbivores

    Science.gov (United States)

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

    2013-01-01

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

  6. The secreted Candida albicans protein Pra1 disrupts host defense by broadly targeting and blocking complement C3 and C3 activation fragments.

    Science.gov (United States)

    Luo, Shanshan; Dasari, Prasad; Reiher, Nadine; Hartmann, Andrea; Jacksch, Susanne; Wende, Elisabeth; Barz, Dagmar; Niemiec, Maria Joanna; Jacobsen, Ilse; Beyersdorf, Niklas; Hünig, Thomas; Klos, Andreas; Skerka, Christine; Zipfel, Peter F

    2018-01-01

    Candida albicans the most frequently isolated clinical fungal pathogen can cause local as well as systemic and life-threatening infections particularly in immune-compromised individuals. A better and more detailed understanding how C. albicans evades human immune attack is therefore needed for identifying fungal immune-evasive proteins and develop new therapies. Here, we identified Pra1, the pH-regulated C. albicans antigen as a hierarchical complement inhibitor that targets C3, the central human complement component. Pra1 cleaved C3 at a unique site and further inhibited effector function of the activation fragments. The newly formed C3a-like peptide lacked the C-terminal arginine residue needed for C3a-receptor binding and activation. Moreover, Pra1 also blocked C3a-like antifungal activity as shown in survival assays, and the C3b-like molecule formed by Pra1 was degraded by the host protease Factor I. Pra1 also bound to C3a and C3b generated by human convertases and blocked their effector functions, like C3a antifungal activity shown by fungal survival, blocked C3a binding to human C3a receptor-expressing HEK cells, activation of Fura2-AM loaded cells, intracellular Ca 2+ signaling, IL-8 release, C3b deposition, as well as opsonophagocytosis and killing by human neutrophils. Thus, upon infection C. albicans uses Pra1 to destroy C3 and to disrupt host complement attack. In conclusion, candida Pra1 represents the first fungal C3-cleaving protease identified and functions as a fungal master regulator of innate immunity and as a central fungal immune-escape protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Stage-specific excretory-secretory small heat shock proteins from the parasitic nematode Strongyloides ratti--putative links to host's intestinal mucosal defense system.

    Science.gov (United States)

    Younis, Abuelhassan Elshazly; Geisinger, Frank; Ajonina-Ekoti, Irene; Soblik, Hanns; Steen, Hanno; Mitreva, Makedonka; Erttmann, Klaus D; Perbandt, Markus; Liebau, Eva; Brattig, Norbert W

    2011-09-01

    In a search for molecules involved in the interaction between intestinal nematodes and mammalian mucosal host cells, we performed MS to identify excretory-secretory proteins from Strongyloides ratti. In the excretory-secretory proteins of the parasitic female stage, we detected, in addition to other peptides, peptides homologous with the Caenorhabditis elegans heat shock protein (HSP)-17, named Sra-HSP-17.1 (∼ 19 kDa) and Sra-HSP-17.2 (∼ 18 kDa), with 49% amino acid identity. The full-length cDNAs (483 bp and 474 bp, respectively) were identified, and the genomic organization was analyzed. To allow further characterization, the proteins were recombinantly expressed and purified. Profiling of transcription by quantitative real-time-PCR and of protein by ELISA in various developmental stages revealed parasitic female-specific expression. Sequence analyses of both the DNA and amino acid sequences showed that the two proteins share a conserved α-crystallin domain and variable N-terminals. The Sra-HSP-17s showed the highest homology with the deduced small HSP sequence of the human pathogen Strongyloides stercoralis. We observed strong immunogenicity of both proteins, leading to strong IgG responses following infection of rats. Flow cytometric analysis indicated the binding of Sra-HSP-17s to the monocyte-macrophage lineage but not to peripheral lymphocytes or neutrophils. A rat intestinal epithelial cell line showed dose-dependent binding to Sra-HSP-17.1, but not to Sra-HSP-17.2. Exposed monocytes released interleukin-10 but not tumor necrosis factor-α in response to Sra-HSP-17s, suggesting the possible involvement of secreted female proteins in host immune responses. © 2011 The Authors Journal compilation © 2011 FEBS.

  8. A cupin domain-containing protein with a quercetinase activity (VdQase regulates Verticillium dahliae’s pathogenicity and contributes to counteracting host defenses

    Directory of Open Access Journals (Sweden)

    Abdel eElHadrami

    2015-06-01

    Full Text Available We previously identified rutin as part of potato root responses to its pathogen Verticillium dahliae. Rutin was directly toxic to the pathogen at doses greater than 160 μM, a threshold below which many V. dahliae pathogenicity-related genes were up-regulated. We identified and characterized a cupin domain-containing protein (VdQase with a dioxygenase activity and a potential role in V. dahliae-potato interactions. The pathogenicity of VdQase knock-out mutants generated through Agrobacterium tumefasciens-mediated transformation was significantly reduced on susceptible potato cultivar Kennebec compared to wild type isolates. Fluorescence microscopy revealed a higher accumulation of flavonols in the stems of infected potatoes and a higher concentration of rutin in the leaves in response to the VdQase mutants as compared to wild type isolates. This, along with the HPLC characterization of high residual and non-utilized quercetin in presence of the knockout mutants, indicates the involvement of VdQase in the catabolism of quercetin and possibly other flavonols in planta. Quantification of Salicylic and Jasmonic Acids (SA, JA in response to the mutants versus wild type isolates revealed involvement of VdQase in the interference with signaling, suggesting a role in pathogenicity. It is hypothesized that the by-product of dioxygenation 2-protocatechuoylphloroglucinolcarboxylic acid, after dissociating into phloroglucinol and protocatechuoyl moieties, becomes a starting point for benzoic acid and SA, thereby interfering with the JA pathway and affecting the interaction outcome. These events may be key factors for V. dahliae in countering potato defenses and becoming notorious in the rhizosphere.

  9. HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection.

    Science.gov (United States)

    Jiang, Guochun; Santos Rocha, Clarissa; Hirao, Lauren A; Mendes, Erica A; Tang, Yuyang; Thompson, George R; Wong, Joseph K; Dandekar, Satya

    2017-05-02

    Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV) infection and viral evasion by utilizing human CD4 + T cell cultures in vitro and a simian immunodeficiency virus (SIV) model of AIDS in vivo Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4 + T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR) to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV in vitro as well as ex vivo in the primary CD4 + T cells isolated from patients receiving suppressive antiretroviral therapy (ART). In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy. IMPORTANCE Understanding how HIV overcomes host antiviral innate defense response in order to establish infection and dissemination is critical for developing prevention and

  10. Cathelicidin-WA Improves Intestinal Epithelial Barrier Function and Enhances Host Defense against Enterohemorrhagic Escherichia coli O157:H7 Infection.

    Science.gov (United States)

    Yi, Hongbo; Hu, Wangyang; Chen, Shan; Lu, Zeqing; Wang, Yizhen

    2017-02-15

    Impaired epithelial barrier function disrupts immune homeostasis and increases inflammation in intestines, leading to many intestinal diseases. Cathelicidin peptides suppress intestinal inflammation and improve intestinal epithelial barrier function independently of their antimicrobial activity. In this study, we investigated the effects of Cathelicidin-WA (CWA) on intestinal epithelial barrier function, as well as the underlying mechanism, by using enterohemorrhagic Escherichia coli (EHEC)-infected mice and intestinal epithelial cells. The results showed that CWA attenuated EHEC-induced clinical symptoms and intestinal colitis, as did enrofloxacin (Enro). CWA decreased IL-6 production in the serum, jejunum, and colon of EHEC-infected mice. Additionally, CWA alleviated the EHEC-induced disruption of mucin-2 and goblet cells in the intestine. Interestingly, CWA increased the mucus layer thickness, which was associated with increasing expression of trefoil factor 3, in the jejunum of EHEC-infected mice. CWA increased the expression of tight junction proteins in the jejunum of EHEC-infected mice. Using intestinal epithelial cells and a Rac1 inhibitor in vitro, we demonstrated that the CWA-mediated increases in the tight junction proteins might depend on the Rac1 pathway. Furthermore, CWA improved the microbiota and short-chain fatty acid concentrations in the cecum of EHEC-infected mice. Although Enro and CWA had similar effects on intestinal inflammation, CWA was superior to Enro with regard to improving intestinal epithelial barrier and microbiota in the intestine. In conclusion, CWA attenuated EHEC-induced inflammation, intestinal epithelial barrier damage, and microbiota disruption in the intestine of mice, suggesting that CWA may be an effective therapy for many intestinal diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  11. HIV Exploits Antiviral Host Innate GCN2-ATF4 Signaling for Establishing Viral Replication Early in Infection

    Directory of Open Access Journals (Sweden)

    Guochun Jiang

    2017-05-01

    Full Text Available Antiviral innate host defenses against acute viral infections include suppression of host protein synthesis to restrict viral protein production. Less is known about mechanisms by which viral pathogens subvert host antiviral innate responses for establishing their replication and dissemination. We investigated early innate defense against human immunodeficiency virus (HIV infection and viral evasion by utilizing human CD4+ T cell cultures in vitro and a simian immunodeficiency virus (SIV model of AIDS in vivo. Our data showed that early host innate defense against the viral infection involves GCN2-ATF4 signaling-mediated suppression of global protein synthesis, which is exploited by the virus for supporting its own replication during early viral infection and dissemination in the gut mucosa. Suppression of protein synthesis and induction of protein kinase GCN2-ATF4 signaling were detected in the gut during acute SIV infection. These changes diminished during chronic viral infection. HIV replication induced by serum deprivation in CD4+ T cells was linked to the induction of ATF4 that was recruited to the HIV long terminal repeat (LTR to promote viral transcription. Experimental inhibition of GCN2-ATF4 signaling either by a specific inhibitor or by amino acid supplementation suppressed the induction of HIV expression. Enhancing ATF4 expression through selenium administration resulted in reactivation of latent HIV in vitro as well as ex vivo in the primary CD4+ T cells isolated from patients receiving suppressive antiretroviral therapy (ART. In summary, HIV/SIV exploits the early host antiviral response through GCN2-ATF4 signaling by utilizing ATF4 for activating the viral LTR transcription to establish initial viral replication and is a potential target for HIV prevention and therapy.

  12. Distinct determinants in HIV-1 Vif and human APOBEC3 proteins are required for the suppression of diverse host anti-viral proteins.

    Directory of Open Access Journals (Sweden)

    Wenyan Zhang

    Full Text Available APOBEC3G (A3G and related cytidine deaminases of the APOBEC3 family of proteins are potent inhibitors of many retroviruses, including HIV-1. Formation of infectious HIV-1 requires the suppression of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the common mechanism of recruiting the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized.In the present study, we have demonstrated that the regions of APOBEC3F (A3F that are required for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation. We also observed that the domains of HIV-1 Vif that are uniquely required for its functional interaction with full-length A3F are also required for the degradation of the C-CDD of A3F; in contrast, those Vif domains that are uniquely required for functional interaction with A3G are not required for the degradation of the C-CDD of A3F. Interestingly, the HIV-1 Vif domains required for the degradation of A3F are also required for the degradation of A3C and A3DE. On the other hand, the Vif domains uniquely required for the degradation of A3G are dispensable for the degradation of cytidine deaminases A3C and A3DE.Our data suggest that distinct regions of A3F and A3G are targeted by HIV-1 Vif molecules. However, HIV-1 Vif suppresses A3F, A3C, and A3DE through similar recognition determinants, which are conserved among Vif molecules from diverse HIV-1 strains. Mapping these determinants may be useful for the design of novel anti-HIV inhibitors.

  13. The frog skin host-defense peptide frenatin 2.1S enhances recruitment, activation and tumoricidal capacity of NK cells.

    Science.gov (United States)

    Pantic, Jelena M; Jovanovic, Ivan P; Radosavljevic, Gordana D; Gajovic, Nevena M; Arsenijevic, Nebojsa N; Conlon, J Michael; Lukic, Miodrag L

    2017-07-01

    Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity. A single injection of frenatin 2.1S (100μg) in BALB/c mice increased the presence of peritoneal CD11c + dendritic cells and CD3 + T cells 24h after administration and there was a significant increase in the number of IL-17 and CXCR3 expressing inflammatory T cells. Frenatin 2.1S treatment also increased the number of TNF-α expressing F4/80 + proinflammatory M1 macrophages. The most striking finding of the study is the marked increase of the number of peritoneal natural killer (NK) cells following frenatin 2.1S injection. Further, frenatin 2.1S administration led to activation of NK cells as evaluated by increased expression of NKG2D, FasL, CD69 and CD107a. The increased ratio of interferon-γ vs. IL-10 producing NK cells is further indication of the proinflammatory action of frenatin 2.1S. Peptide treatment enhanced the tumoricidal action of peritoneal NK cells on 4T1 mouse mammary carcinoma cells as revealed by the real-time automated monitoring of cell status. Our data demonstrate that frenatin 2.1S promotes activation and cytotoxic capacity of NK cells and should be regarded as a candidate for antitumor immunotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Host defense and recruitment of Foxp3⁺ T regulatory cells to the lungs in chronic Mycobacterium tuberculosis infection requires toll-like receptor 2.

    Directory of Open Access Journals (Sweden)

    Amanda McBride

    Full Text Available Acute resistance to low dose M. tuberculosis (Mtb infection is not dependent on Toll-like receptor (TLR 2. However, whether TLR2 contributes to resistance in chronic Mtb infection has remained uncertain. Here we report that, following low dose aerosol infection with Mtb, mice lacking TLR2 (TLR2KO, in comparison with wild type (WT mice, exhibit enhanced cellular infiltration and inflammation in the lungs, and fail to stably control bacterial burden during chronic infection. IFNγ and IL-17 was expressed at equivalent levels in the two groups; however, the characteristic accumulation of Foxp3⁺ T regulatory cells (Tregs in pulmonary granulomas was significantly reduced in TLR2KO mice. Nonetheless, this reduction in Tregs was independent of whether Tregs expressed TLR2 or not. To directly link the reduced number of Tregs to the increased inflammation present in the TLR2KO mice, we used a macrophage adoptive transfer model. At seven weeks post-Mtb infection, TLR2KO mice, which were adoptively transferred with WT macrophages, displayed enhanced accumulation of Tregs in the lungs and a concomitant reduction in inflammation in contrast with control mice that received TLR2KO macrophages. However, the pulmonary bacterial burden between the two groups remained similar indicating that TLR2's role in modulating immunopathology is functionally distinct from its role in restricting Mtb growth in chronic infection. Together, these findings unequivocally demonstrate that TLR2 contributes to host resistance against chronic Mtb infection and reveal a novel role for TLR2 in mediating the recruitment of Foxp3⁺ Tregs to the lungs to control inflammation.

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

    Science.gov (United States)

    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.

  16. Suppression of host-seeking Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae) nymphs after dual applications of plant-derived acaricides in New Jersey.

    Science.gov (United States)

    Jordan, Robert A; Dolan, Marc C; Piesman, Joseph; Schulze, Terry L

    2011-04-01

    We evaluated the ability of dual applications of natural, plant-derived acaricides to suppress nymphal Ixodes scapularis Say and Amblyomma americanum (L.) (Acari: Ixodidae) in a Lyme disease endemic area of New Jersey. An aqueous formulation of 2% nootkatone provided >90% control of I. scapularis through 7 d. Control declined to 80.9% at 14 d, and a second application was made that provided >95% control through the remaining 4 wk of the nymphal season. Nootkatone provided >90% control of A. americanum through 35 d postapplication. Applications of 2% carvacrol and EcoTrol T&O resulted in rapid knockdown of both tick species, but control declined significantly to 76.7 and 73.7%, respectively, after 14 d when a second application was made that extended control of both tick species to between 86.2 and 94.8% at 21 d. Subsequently, control declined steadily in all plots by 42 d postapplication except for I. scapularis in carvacrol-treated plots, where levels of control >90% were observed through 35 d. Of the three compounds tested, 2% nootkatone provided the most consistent results, with 96.5 and 91.9% control of I. scapularis and A. americanum through 42 and 35 d, respectively. The ability of plant-derived natural products to quickly suppress and maintain significant control of populations of these medically important ticks may represent a future alternative to the use of conventional synthetic acaricides. In addition, the demonstrated efficacy of properly-timed backpack sprayer application may enable homeowner access to these minimal-risk acaricides.

  17. Active suppression of host-vs-graft reaction in pregnant mice. VI. Soluble suppressor activity obtained from decidua of allopregnant mice blocks the response to IL 2.

    Science.gov (United States)

    Clark, D A; Chaput, A; Walker, C; Rosenthal, K L

    1985-03-01

    The mammalian fetus expresses a variety of antigens against which the maternal immune system can react and which in an allogeneic mating bears paternal transplantation antigens. Although these antigens may be expressed on the fetal trophoblast cells that contact maternal uterine decidua, the "fetal allograft" is not usually rejected. Previous studies have demonstrated the presence of nonspecific non-thymus-derived suppressor cells in the lymph nodes draining the uterus and in decidua of laboratory mice undergoing first allogeneic pregnancy. These suppressor cells appeared to be small lymphocyte cells that inhibit the generation of cytotoxic T lymphocytes (CTL) in vitro and in vivo and elaborate a nonspecific non-MHC-restricted soluble suppressor activity when cultured for 48 hours at 37 degrees C in vitro. We now report that soluble suppressor activity obtained from the decidua (DS) of allopregnant C3H/HeJ mice inhibits both the primary and secondary (memory) CTL response in vitro but does not inhibit lysis of target cells by preformed CTL. DS did not suppress the proliferation of YAC lymphoma cells, P-815 cells, or a C3H placental trophoblastoma line. Suppressor activity was obtained from anti-thy-1.2 + complement-resistant cells in the decidua, could also be obtained from the decidua of allopregnant CD1 nu/nu mice, and was associated with a single peak of activity of approximately 100,000 daltons on Sephacryl 200 chromatography. Suppression could not be overcome by adding either crude or HPLC-purified IL 2 to the mixed lymphocyte cultures in vitro, and both crude and column-purified suppressor factor inhibited the IL 2-dependent proliferation of H-Y cells (a cloned T cell line with NK activity). Furthermore, DS inhibited the IL 2-dependent generation of cytotoxic effector cells in vitro in the absence of allogeneic stimulator cells. Thus, a soluble suppressor factor obtained from non-T cells present in the decidua of successfully allopregnant mice could block the

  18. Radix isatidis Polysaccharides Inhibit Influenza a Virus and Influenza A Virus-Induced Inflammation via Suppression of Host TLR3 Signaling In Vitro

    Directory of Open Access Journals (Sweden)

    Zhengtu Li

    2017-01-01

    Full Text Available Influenza remains one of the major epidemic diseases worldwide, and rapid virus replication and collateral lung tissue damage caused by excessive pro-inflammatory host immune cell responses lead to high mortality rates. Thus, novel therapeutic agents that control influenza A virus (IAV propagation and attenuate excessive pro-inflammatory responses are needed. Polysaccharide extract from Radix isatidis, a traditional Chinese herbal medicine, exerted potent anti-IAV activity against human seasonal influenza viruses (H1N1 and H3N2 and avian influenza viruses (H6N2 and H9N2 in vitro. The polysaccharides also significantly reduced the expression of pro-inflammatory cytokines (IL-6 and chemokines (IP-10, MIG, and CCL-5 stimulated by A/PR/8/34 (H1N1 at a range of doses (7.5 mg/mL, 15 mg/mL, and 30 mg/mL; however, they were only effective against progeny virus at a high dose. Similar activity was detected against inflammation induced by avian influenza virus H9N2. The polysaccharides strongly inhibited the protein expression of TLR-3 induced by PR8, suggesting that they impair the upregulation of pro-inflammatory factors induced by IAV by inhibiting activation of the TLR-3 signaling pathway. The polysaccharide extract from Radix isatidis root therefore has the potential to be used as an adjunct to antiviral therapy for the treatment of IAV infection.

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

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    Amey Redkar

    2017-05-01

    Full Text Available 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.

  20. Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity.

    Science.gov (United States)

    Fedele, Giorgio; Schiavoni, Ilaria; Adkins, Irena; Klimova, Nela; Sebo, Peter

    2017-09-21

    Adenylate cyclase toxin (CyaA) is released in the course of B. pertussis infection in the host's respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC), macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3',5'-cyclic adenosine monophosphate (cAMP), which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.

  1. Key roles of glutamate metabolism and cuticle permeability in the multifaceted defense response of the abscisic acid deficient sitiens tomato mutant against Botrytis cinerea

    OpenAIRE

    Seifi, Hamed

    2013-01-01

    As the inevitable result of a ping-pong-type co-evolution, plants have devised sophisticated defense mechanisms to cope with the constant threat of pathogenic microorganisms. These mechanisms are diverse, varying from constructing physical barriers in order to mechanically halt pathogen penetration, to de novo synthesis of various anti-microbial compounds in order to chemically suppress pathogen growth in the host tissue. On the other hand, pathogens have also developed different virulence me...

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

    KAUST Repository

    Ali, Shawkat

    2015-08-11

    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.

  3. P17, an Original Host Defense Peptide from Ant Venom, Promotes Antifungal Activities of Macrophages through the Induction of C-Type Lectin Receptors Dependent on LTB4-Mediated PPARγ Activation

    Directory of Open Access Journals (Sweden)

    Khaddouj Benmoussa

    2017-11-01

    Full Text Available Despite the growing knowledge with regard to the immunomodulatory properties of host defense peptides, their impact on macrophage differentiation and on its associated microbicidal functions is still poorly understood. Here, we demonstrated that the P17, a new cationic antimicrobial peptide from ant venom, induces an alternative phenotype of human monocyte-derived macrophages (h-MDMs. This phenotype is characterized by a C-type lectin receptors (CLRs signature composed of mannose receptor (MR and Dectin-1 expression. Concomitantly, this activation is associated to an inflammatory profile characterized by reactive oxygen species (ROS, interleukin (IL-1β, and TNF-α release. P17-activated h-MDMs exhibit an improved capacity to recognize and to engulf Candida albicans through the overexpression both of MR and Dectin-1. This upregulation requires arachidonic acid (AA mobilization and the activation of peroxisome proliferator-activated receptor gamma (PPARγ nuclear receptor through the leukotriene B4 (LTB4 production. AA/LTB4/PPARγ/Dectin-1-MR signaling pathway is crucial for P17-mediated anti-fungal activity of h-MDMs, as indicated by the fact that the activation of this axis by P17 triggered ROS production and inflammasome-dependent IL-1β release. Moreover, we showed that the increased anti-fungal immune response of h-MDMs by P17 was dependent on intracellular calcium mobilization triggered by the interaction of P17 with pertussis toxin-sensitive G-protein-coupled receptors on h-MDMs. Finally, we also demonstrated that P17-treated mice infected with C. albicans develop less severe gastrointestinal infection related to a higher efficiency of their macrophages to engulf Candida, to produce ROS and IL-1β and to kill the yeasts. Altogether, these results identify P17 as an original activator of the fungicidal response of macrophages that acts upstream PPARγ/CLRs axis and offer new immunomodulatory therapeutic perspectives in the field of

  4. Frequency and Distribution of Single-Nucleotide Polymorphisms within mprF in Methicillin-Resistant Staphylococcus aureus Clinical Isolates and Their Role in Cross-Resistance to Daptomycin and Host Defense Antimicrobial Peptides.

    Science.gov (United States)

    Bayer, Arnold S; Mishra, Nagendra N; Chen, Liang; Kreiswirth, Barry N; Rubio, Aileen; Yang, Soo-Jin

    2015-08-01

    MprF is responsible for the lysinylation of phosphatidylglycerol (PG) to synthesize the positively charged phospholipid (PL) species, lysyl-PG (L-PG). It has been proposed that the single-nucleotide polymorphisms (SNPs) within the mprF open reading frame (ORF) are associated with a gain-in-function phenotype in terms of daptomycin resistance in Staphylococcus aureus. (Note that although the official term is daptomycin nonsusceptibility, we use the term daptomycin resistance in this paper for ease of presentation.) Using 22 daptomycin-susceptible (DAP(s))/daptomycin-resistant (DAP(r)) clinical methicillin-resistant S. aureus (MRSA) strain pairs, we assessed (i) the frequencies and distribution of putative mprF gain-in-function SNPs, (ii) the relationships of the SNPs to both daptomycin resistance and cross-resistance to the prototypical endovascular host defense peptide (HDP) thrombin-induced platelet microbicidal protein (tPMP), and (iii) the impact of mprF SNPs on positive surface charge phenotype and modifications of membrane PL profiles. Most of the mprF SNPs identified in our DAP(r) strains were clustered within the two MprF loci, (i) the central bifunctional domain and (ii) the C-terminal synthase domain. Moreover, we were able to correlate the presence and location of mprF SNPs in DAP(r) strains with HDP cross-resistance, positive surface charge, and L-PG profiles. Although DAP(r) strains with mprF SNPs in the bifunctional domain showed higher resistance to tPMPs than DAP(r) strains with SNPs in the synthase domain, this relationship was not observed in positive surface charge assays. These results demonstrated that both charge-mediated and -unrelated mechanisms are involved in DAP resistance and HDP cross-resistance in S. aureus. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Antimicrobial peptides in echinoderm host defense.

    Science.gov (United States)

    Li, Chun; Blencke, Hans-Matti; Haug, Tor; Stensvåg, Klara

    2015-03-01

    Antimicrobial peptides (AMPs) are important effector molecules in innate immunity. Here we briefly summarize characteristic traits of AMPs and their mechanisms of antimicrobial activity. Echinoderms live in a microbe-rich marine environment and are known to express a wide range of AMPs. We address two novel AMP families from coelomocytes of sea urchins: cysteine-rich AMPs (strongylocins) and heterodimeric AMPs (centrocins). These peptide families have conserved preprosequences, are present in both adults and pluteus stage larvae, have potent antimicrobial properties, and therefore appear to be important innate immune effectors. Strongylocins have a unique cysteine pattern compared to other cysteine-rich peptides, which suggests a novel AMP folding pattern. Centrocins and SdStrongylocin 2 contain brominated tryptophan residues in their native form. This review also includes AMPs isolated from other echinoderms, such as holothuroidins, fragments of beta-thymosin, and fragments of lectin (CEL-III). Echinoderm AMPs are crucial molecules for the understanding of echinoderm immunity, and their potent antimicrobial activity makes them potential precursors of novel drug leads. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Host defense mechanisms in oral mucosa

    OpenAIRE

    菅原, 俊二

    2003-01-01

    It is speculated that more than 500 bacterial species reside in the oral cavity. Some cause periodontitis and dental caries, an understanding of which requires examination of innate immunity in the oral cavity. Oral mucosal cells such as epithelial cells and fibroblasts are thought to act as a physical barrier against invasion by pathogenic organisms, but they also can produce inflammatory cytokines and express adhesion molecules, resulting in control of neutrophil and T cell infiltration. Th...

  7. Host Defense Against Opportunist Microorganisms Following Trauma.

    Science.gov (United States)

    1980-09-01

    candidemia or evidence of systemic candidosis were to be correlated with changes in the numbers of Candida isolated from the serial quantitative cultures...compared for their sensitivity and specificity for the detection of Candida antigenemia prior to and during candidemia and systemic candidosis. The...sera contained inhibitory activity had pneumonia, candidemia , and multiple episodes of bacteremia caused by more than one microorganism, and 2 had a

  8. Fungal Recognition and Host Defense Mechanisms

    NARCIS (Netherlands)

    Dambuza, I.M.; Levitz, S.M.; Netea, M.G.; Brown, G.D.

    2017-01-01

    Fungi have emerged as premier opportunistic microbes of the 21st century, having a considerable impact on human morbidity and mortality. The huge increase in incidence of these diseases is largely due to the HIV pandemic and use of immunosuppressive therapies, underscoring the importance of the

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

    Science.gov (United States)

    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.

  10. Negative regulation of defense responses in plants by a conserved MAPKK kinase.

    Science.gov (United States)

    Frye, C A; Tang, D; Innes, R W

    2001-01-02

    The enhanced disease resistance 1 (edr1) mutation of Arabidopsis confers resistance to powdery mildew disease caused by the fungus Erysiphe cichoracearum. Resistance mediated by the edr1 mutation is correlated with induction of several defense responses, including host cell death. Double mutant analysis revealed that all edr1-associated phenotypes are suppressed by mutations that block salicylic acid (SA) perception (nim1) or reduce SA production (pad4 and eds1). The NahG transgene, which lowers endogenous SA levels, also suppressed edr1. In contrast, the ein2 mutation did not suppress edr1-mediated resistance and associated phenotypes, indicating that ethylene and jasmonic acid-induced responses are not required for edr1 resistance. The EDR1 gene was isolated by positional cloning and was found to encode a putative MAP kinase kinase kinase similar to CTR1, a negative regulator of ethylene responses in Arabidopsis. Taken together, these data suggest that EDR1 functions at the top of a MAP kinase cascade that negatively regulates SA-inducible defense responses. Putative orthologs of EDR1 are present in monocots such as rice and barley, indicating that EDR1 may regulate defense responses in a wide range of crop species.

  11. Myeloid cell sirtuin-1 expression does not alter host immune responses to Gram-negative endotoxemia or Gram-positive bacterial infection.

    Directory of Open Access Journals (Sweden)

    Laura E Crotty Alexander

    Full Text Available The role of sirtuin-1 (SIRT1 in innate immunity, and in particular the influence of SIRT1 on antimicrobial defense against infection, has yet to be reported but is important to define since SIRT1 inhibitors are being investigated as therapeutic agents in the treatment of cancer, Huntington's disease, and autoimmune diseases. Given the therapeutic potential of SIRT1 suppression, we sought to characterize the role of SIRT1 in host defense. Utilizing both pharmacologic methods and a genetic knockout, we demonstrate that SIRT1 expression has little influence on macrophage and neutrophil antimicrobial functions. Myeloid SIRT1 expression does not change mortality in gram-negative toxin-induced shock or gram-positive bacteremia, suggesting that therapeutic suppression of SIRT1 may be done safely without suppression of myeloid cell-specific immune responses to severe bacterial infections.

  12. NAD1 Controls Defense-Like Responses in Medicago truncatula Symbiotic Nitrogen Fixing Nodules Following Rhizobial Colonization in a BacA-Independent Manner.

    Science.gov (United States)

    Domonkos, Ágota; Kovács, Szilárd; Gombár, Anikó; Kiss, Ernő; Horváth, Beatrix; Kováts, Gyöngyi Z; Farkas, Attila; Tóth, Mónika T; Ayaydin, Ferhan; Bóka, Károly; Fodor, Lili; Ratet, Pascal; Kereszt, Attila; Endre, Gabriella; Kaló, Péter

    2017-12-14

    Legumes form endosymbiotic interaction with host compatible rhizobia, resulting in the development of nitrogen-fixing root nodules. Within symbiotic nodules, rhizobia are intracellularly accommodated in plant-derived membrane compartments, termed symbiosomes. In mature nodule, the massively colonized cells tolerate the existence of rhizobia without manifestation of visible defense responses, indicating the suppression of plant immunity in the nodule in the favur of the symbiotic partner. Medicago truncatula DNF2 (defective in nitrogen fixation 2) and NAD1 (nodules with activated defense 1) genes are essential for the control of plant defense during the colonization of the nitrogen-fixing nodule and are required for bacteroid persistence. The previously identified nodule-specific NAD1 gene encodes a protein of unknown function. Herein, we present the analysis of novel NAD1 mutant alleles to better understand the function of NAD1 in the repression of immune responses in symbiotic nodules. By exploiting the advantage of plant double and rhizobial mutants defective in establishing nitrogen-fixing symbiotic interaction, we show that NAD1 functions following the release of rhizobia from the infection threads and colonization of nodule cells. The suppression of plant defense is self-dependent of the differentiation status of the rhizobia. The corresponding phenotype of nad1 and dnf2 mutants and the similarity in the induction of defense-associated genes in both mutants suggest that NAD1 and DNF2 operate close together in the same pathway controlling defense responses in symbiotic nodules.

  13. Viral RNase3 Co-Localizes and Interacts with the Antiviral Defense Protein SGS3 in Plant Cells

    Science.gov (United States)

    Weinheimer, Isabel; Haikonen, Tuuli; Ala-Poikela, Marjo; Moser, Mirko; Streng, Janne; Rajamäki, Minna-Liisa; Valkonen, Jari P. T.

    2016-01-01

    Sweet potato chlorotic stunt virus (SPCSV; family Closteroviridae) encodes a Class 1 RNase III endoribonuclease (RNase3) that suppresses post-transcriptional RNA interference (RNAi) and eliminates antiviral defense in sweetpotato plants (Ipomoea batatas). For RNAi suppression, RNase3 cleaves double-stranded small interfering RNAs (ds-siRNA) and long dsRNA to fragments that are too short to be utilized in RNAi. However, RNase3 can suppress only RNAi induced by sense RNA. Sense-mediated RNAi involves host suppressor of gene silencing 3 (SGS3) and RNA–dependent RNA polymerase 6 (RDR6). In this study, subcellular localization and host interactions of RNase3 were studied in plant cells. RNase3 was found to interact with SGS3 of sweetpotato and Arabidopsis thaliana when expressed in leaves, and it localized to SGS3/RDR6 bodies in the cytoplasm of leaf cells and protoplasts. RNase3 was also detected in the nucleus. Co-expression of RNase3 and SGS3 in leaf tissue enhanced the suppression of RNAi, as compared with expression of RNase3 alone. These results suggest additional mechanisms needed for efficient RNase3-mediated suppression of RNAi and provide new information about the subcellular context and phase of the RNAi pathway in which RNase3 realizes RNAi suppression. PMID:27391019

  14. Invasion of Dendritic Cells, Macrophages and Neutrophils by the Bordetella Adenylate Cyclase Toxin: A Subversive Move to Fool Host Immunity

    Directory of Open Access Journals (Sweden)

    Giorgio Fedele

    2017-09-01

    Full Text Available Adenylate cyclase toxin (CyaA is released in the course of B. pertussis infection in the host’s respiratory tract in order to suppress its early innate and subsequent adaptive immune defense. CD11b-expressing dendritic cells (DC, macrophages and neutrophils are professional phagocytes and key players of the innate immune system that provide a first line of defense against invading pathogens. Recent findings revealed the capacity of B. pertussis CyaA to intoxicate DC with high concentrations of 3′,5′-cyclic adenosine monophosphate (cAMP, which ultimately skews the host immune response towards the expansion of Th17 cells and regulatory T cells. CyaA-induced cAMP signaling swiftly incapacitates opsonophagocytosis, oxidative burst and NO-mediated killing of bacteria by neutrophils and macrophages. The subversion of host immune responses by CyaA after delivery into DC, macrophages and neutrophils is the subject of this review.

  15. Suppressed Belief

    Directory of Open Access Journals (Sweden)

    Komarine Romdenh-Romluc

    2009-12-01

    Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

  16. Host-pathogen interactions in Campylobacter infections: the host perspective

    NARCIS (Netherlands)

    Janssen, R.; Krogfelt, K.A.; Cawthraw, S.A.; Pelt, van W.; Wagenaar, J.A.; Owen, R.J.

    2008-01-01

    Campylobacter is a major cause of acute bacterial diarrhea in humans worldwide. This study was aimed at summarizing the current understanding of host mechanisms involved in the defense against Campylobacter by evaluating data available from three sources: (i) epidemiological observations, (ii)

  17. Antioxidative defense

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2011-01-01

    Full Text Available Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar, to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules.

  18. Immunoregulation by Trichinella spiralis: Benefits for parasite and host

    NARCIS (Netherlands)

    Aranzamendi Esteban, C.R.|info:eu-repo/dai/nl/341157430

    2013-01-01

    Several studies indicate that certain helminths suppress the host immune responses. This suppression may benefit the parasite since it increases the chances of survival in their host. By doing so, the hosts may also benefit due to concomitant reduction of immune pathology associated with allergies

  19. First in Vivo Batrachochytrium dendrobatidis Transcriptomes Reveal Mechanisms of Host Exploitation, Host-Specific Gene Expression, and Expressed Genotype Shifts

    OpenAIRE

    Amy R. Ellison; Graziella V. DiRenzo; Caitlin A. McDonald; Karen R. Lips; Kelly R. Zamudio

    2017-01-01

    For generalist pathogens, host species represent distinct selective environments, providing unique challenges for resource acquisition and defense from host immunity, potentially resulting in host-dependent differences in pathogen fitness. Gene expression modulation should be advantageous, responding optimally to a given host and mitigating the costs of generalism. Batrachochytrium dendrobatidis (Bd), a fungal pathogen of amphibians, shows variability in pathogenicity among isolates, and with...

  20. Host Defence to Pulmonary Mycosis

    Directory of Open Access Journals (Sweden)

    Christopher H Mody

    1999-01-01

    Full Text Available OBJECTIVE: To provide a basic understanding of the mechanisms of host defense to pathogenic fungi. This will help physicians understand why some patients are predisposed to fungal infections and update basic scientists on how microbial immunology applies to fungal disease.

  1. Suppressing autoimmunity in Arabidopsis thaliana with dominant negative immune receptors

    DEFF Research Database (Denmark)

    Greeff, Michael Christiaan

    R genes, as we have recently found that transgenics with similarly mutated rpm1-DN alleles lose resistance to Pseudomonas syringae expressing the AvrRpm1 effector. Accordingly, we have constructed a collection of 100 R-DN alleles and transformed them into other autoimmune mutants including camta3......A small set of Resistance proteins (R-proteins), guards plants against a large set of pathogen effector proteins that can suppress or subvert plant defense responses. The guard model attempts to solve this discrepancy by proposing that a major function of R proteins is to monitor host effector...... Cell Death 11 (acd11) leads to inappropriate activation of hypersensitive cell death. We have previously performed a large-scale survival screen for suppressors of acd11 and found that cell death in acd11 is suppressed by mutations in a gene encoding an R protein. We have thus proposed that loss of ACD...

  2. Suppressing autoimmunity in Arabidopsis thaliana with dominant negative immune receptors

    DEFF Research Database (Denmark)

    Greeff, Michael Christiaan

    Cell Death 11 (acd11) leads to inappropriate activation of hypersensitive cell death. We have previously performed a large-scale survival screen for suppressors of acd11 and found that cell death in acd11 is suppressed by mutations in a gene encoding an R protein. We have thus proposed that loss of ACD......11 results in HR cell death because LAZ5 directly or indirectly guards it. The LAZ5 alleles we first found were dominant negative (laz5-DN). The laz-DN allele mutation was found in a conserved functionally important ATP binding region, the P-loop. Site-directed DN mutant alleles can be made for other......A small set of Resistance proteins (R-proteins), guards plants against a large set of pathogen effector proteins that can suppress or subvert plant defense responses. The guard model attempts to solve this discrepancy by proposing that a major function of R proteins is to monitor host effector...

  3. Host genetics affect microbial ecosystems via host immunity.

    Science.gov (United States)

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

    2016-10-01

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

  4. The ecology and evolution of inducible defenses.

    Science.gov (United States)

    Harvell, C D

    1990-09-01

    Inducible defenses are responses activated through a previous encounter with a consumer or competitor that confer some degree of resistance to subsequent attacks. While the importance of inducible resistance has long been known in host-parasite interactions, it is only recently that its importance has emerged in other natural systems. Although the structural defenses produced by invertebrates to their competitors and predators are by no means the same as an immune response triggered by parasites, these responses all share the properties of (1) specificity, (2) amplification and (3) memory. This review discusses the following ecological consequences and evolutionary causes of inducible defenses: (1) Inducible defenses render historical factors important in biological interactions and can affect the probability of individual survival and growth, as well as affect population dynamics of consumers in some circumstances. (2) Although the benefits of inducible defenses are often balanced by fitness costs, including reduced growth, reproductive output and survivorship, the role of costs and benefits in the evolution of inducible defenses is by no means clear. A more integrated approach would involve a multivariate analysis of the role of natural selection on the inducible characters of interest, their norms of reaction and correlated fitness characters. (3) The disproportionate representation of inducible, morphological defenses among clonal organisms may be due to both a higher rate of origination and enhanced selection to maintain these defenses in clonal taxa. (4) Inducible defenses should be most common when reliable cues are available, attacks by biological agents are unpredictable, and the fitness gains of defenses are balanced by the costs. An integrated approach to studying inducible defenses would thus combine mechanistic estimates of costs, population-level estimates of defense effectiveness, and genetic estimates of correlations between fitness and inducible

  5. Expression profile of host restriction factors in HIV-1 elite controllers.

    Science.gov (United States)

    Abdel-Mohsen, Mohamed; Raposo, Rui André Saraiva; Deng, Xutao; Li, Manqing; Liegler, Teri; Sinclair, Elizabeth; Salama, Mohamed S; Ghanem, Hussam El-Din A; Hoh, Rebecca; Wong, Joseph K; David, Michael; Nixon, Douglas F; Deeks, Steven G; Pillai, Satish K

    2013-10-16

    Several host-encoded antiviral factors suppress HIV-1 replication in a cell-autonomous fashion in vitro. The relevance of these defenses to the control of HIV-1 in vivo remains to be elucidated. We hypothesized that cellular restriction of HIV-1 replication plays a significant role in the observed suppression of HIV-1 in "elite controllers", individuals who maintain undetectable levels of viremia in the absence of antiretroviral therapy (ART). We comprehensively compared the expression levels of 34 host restriction factors and cellular activation levels in CD4+ T cells and sorted T cell subsets between elite controllers, HIV-1-infected (untreated) non-controllers, ART-suppressed, and uninfected individuals. Expression of schlafen 11, a codon usage-based inhibitor of HIV-1 protein synthesis, was significantly elevated in CD4+ T cells from elite controllers as compared to both non-controllers (p = 0.048) and ART-suppressed individuals (p = 0.024), with this effect most apparent in central memory CD4+ T cells. Schlafen 11 expression levels were comparable between controllers and uninfected individuals. Cumulative restriction factor expression was positively correlated with CD4+ T cell activation (r² = 0.597, p < 0.0001), viral load (r² = 0.34, p = 0.015), and expression of ISG15 (r² = 0.73, p < 0.0001), a marker of interferon exposure. APOBEC3C, APOBEC3D, CTR9, TRIM26, and TRIM32 were elevated in elite controllers with respect to ART-suppressed individuals, while levels were comparable to uninfected individuals and non-controllers. Host restriction factor expression typically scales with cellular activation levels. However, the elevated mRNA and protein expression of schlafen 11, despite low activation and viral load, violates the global pattern and may be a signature characteristic of HIV-1 elite control.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  8. Suppression mental questionnaire: a preliminary study

    OpenAIRE

    Salvatore Settineri; Emanuele Maria Merlo; Irene Pagano Dritto; Maria Midili; Antonio Bruno; Carmela Mento

    2016-01-01

    Authors postulate that the difference between suppression and repression, highlighted in particular by the Societè Psychanalitique de Paris, enables the development of a quantitative instrument, since suppression is a defense accessible to consciousness and therefore quantifiable like scales and questionnaires. The idea of constructing a questionnaire, included the identification of thirty variables having somehow a plausible relationship with this mechanism. The factor exploratory analysis w...

  9. Suppression chamber

    International Nuclear Information System (INIS)

    Goto, Hiroshi; Tsuji, Akio.

    1976-01-01

    Purpose: To miniaturize the storage tank of condensated water in BWR reactor. Constitution: A diaphragm is provided in a suppression chamber thereby to partition the same into an inner compartment and an outer compartment. In one of said compartments there is stored clean water to be used for feeding at the time of separating the reactor and for the core spray system, and in another compartment there is stored water necessary for accomplishing the depressurization effect at the time of coolant loss accident. To the compartment in which clean water is stored there is connected a water cleaning device for constantly maintaining water in clean state. As this cleaning device an already used fuel pool cleaning device can be utilized. Further, downcomers for accomplishing the depressurization function are provided in both inner compartment and outer compartment. The capacity of the storage tank can be reduced by the capacity of clean water within the suppression chamber. (Ikeda, J.)

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

    Science.gov (United States)

    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...

  11. Interleukin-35 induces regulatory B cells that suppress autoimmune disease.

    Science.gov (United States)

    Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M; Mahdi, Rashid M; Dolinska, Monika B; Sergeev, Yuri V; Wingfield, Paul T; Kim, Sung-Hye; Egwuagu, Charles E

    2014-06-01

    Interleukin-10 (IL-10)-producing regulatory B (Breg) cells suppress autoimmune disease, and increased numbers of Breg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting CD4(+) T cells to regulatory T (Treg) cells. The mechanisms mediating the induction and development of Breg cells remain unclear. Here we show that IL-35 induces Breg cells and promotes their conversion to a Breg subset that produces IL-35 as well as IL-10. Treatment of mice with IL-35 conferred protection from experimental autoimmune uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL-35 signaling (IL-12Rβ2 KO mice) produced less Breg cells endogenously or after treatment with IL-35 and developed severe uveitis. Adoptive transfer of Breg cells induced by recombinant IL-35 suppressed EAU when transferred to mice with established disease, inhibiting pathogenic T helper type 17 (TH17) and TH1 cells while promoting Treg cell expansion. In B cells, IL-35 activates STAT1 and STAT3 through the IL-35 receptor comprising the IL-12Rβ2 and IL-27Rα subunits. As IL-35 also induced the conversion of human B cells into Breg cells, these findings suggest that IL-35 may be used to induce autologous Breg and IL-35(+) Breg cells and treat autoimmune and inflammatory disease.

  12. Nitric oxide antagonizes the acid tolerance response that protects Salmonella against innate gastric defenses.

    Directory of Open Access Journals (Sweden)

    Travis J Bourret

    2008-03-01

    Full Text Available Reactive nitrogen species (RNS derived from dietary and salivary inorganic nitrogen oxides foment innate host defenses associated with the acidity of the stomach. The mechanisms by which these reactive species exert antimicrobial activity in the gastric lumen are, however, poorly understood.The genetically tractable acid tolerance response (ATR that enables enteropathogens to survive harsh acidity was screened for signaling pathways responsive to RNS. The nitric oxide (NO donor spermine NONOate derepressed the Fur regulon that controls secondary lines of resistance against organic acids. Despite inducing a Fur-mediated adaptive response, acidified RNS largely repressed oral virulence as demonstrated by the fact that Salmonella bacteria exposed to NO donors during mildly acidic conditions were shed in low amounts in feces and exhibited ameliorated oral virulence. NO prevented Salmonella from mounting a de novo ATR, but was unable to suppress an already functional protective response, suggesting that RNS target regulatory cascades but not their effectors. Transcriptional and translational analyses revealed that the PhoPQ signaling cascade is a critical ATR target of NO in rapidly growing Salmonella. Inhibition of PhoPQ signaling appears to contribute to most of the NO-mediated abrogation of the ATR in log phase bacteria, because the augmented acid sensitivity of phoQ-deficient Salmonella was not further enhanced after RNS treatment.Since PhoPQ-regulated acid resistance is widespread in enteric pathogens, the RNS-mediated inhibition of the Salmonella ATR described herein may represent a common component of innate host defenses.

  13. Mechanisms and ecological consequences of plant defence induction and suppression in herbivore communities

    Science.gov (United States)

    Kant, M. R.; Jonckheere, W.; Knegt, B.; Lemos, F.; Liu, J.; Schimmel, B. C. J.; Villarroel, C. A.; Ataide, L. M. S.; Dermauw, W.; Glas, J. J.; Egas, M.; Janssen, A.; Van Leeuwen, T.; Schuurink, R. C.; Sabelis, M. W.; Alba, J. M.

    2015-01-01

    Background Plants are hotbeds for parasites such as arthropod herbivores, which acquire nutrients and energy from their hosts in order to grow and reproduce. Hence plants are selected to evolve resistance, which in turn selects for herbivores that can cope with this resistance. To preserve their fitness when attacked by herbivores, plants can employ complex strategies that include reallocation of resources and the production of defensive metabolites and structures. Plant defences can be either prefabricated or be produced only upon attack. Those that are ready-made are referred to as constitutive defences. Some constitutive defences are operational at any time while others require activation. Defences produced only when herbivores are present are referred to as induced defences. These can be established via de novo biosynthesis of defensive substances or via modifications of prefabricated substances and consequently these are active only when needed. Inducibility of defence may serve to save energy and to prevent self-intoxication but also implies that there is a delay in these defences becoming operational. Induced defences can be characterized by alterations in plant morphology and molecular chemistry and are associated with a decrease in herbivore performance. These alterations are set in motion by signals generated by herbivores. Finally, a subset of induced metabolites are released into the air as volatiles and function as a beacon for foraging natural enemies searching for prey, and this is referred to as induced indirect defence. Scope The objective of this review is to evaluate (1) which strategies plants have evolved to cope with herbivores and (2) which traits herbivores have evolved that enable them to counter these defences. The primary focus is on the induction and suppression of plant defences and the review outlines how the palette of traits that determine induction/suppression of, and resistance/susceptibility of herbivores to, plant defences can

  14. Mechanisms and ecological consequences of plant defence induction and suppression in herbivore communities.

    Science.gov (United States)

    Kant, M R; Jonckheere, W; Knegt, B; Lemos, F; Liu, J; Schimmel, B C J; Villarroel, C A; Ataide, L M S; Dermauw, W; Glas, J J; Egas, M; Janssen, A; Van Leeuwen, T; Schuurink, R C; Sabelis, M W; Alba, J M

    2015-06-01

    Plants are hotbeds for parasites such as arthropod herbivores, which acquire nutrients and energy from their hosts in order to grow and reproduce. Hence plants are selected to evolve resistance, which in turn selects for herbivores that can cope with this resistance. To preserve their fitness when attacked by herbivores, plants can employ complex strategies that include reallocation of resources and the production of defensive metabolites and structures. Plant defences can be either prefabricated or be produced only upon attack. Those that are ready-made are referred to as constitutive defences. Some constitutive defences are operational at any time while others require activation. Defences produced only when herbivores are present are referred to as induced defences. These can be established via de novo biosynthesis of defensive substances or via modifications of prefabricated substances and consequently these are active only when needed. Inducibility of defence may serve to save energy and to prevent self-intoxication but also implies that there is a delay in these defences becoming operational. Induced defences can be characterized by alterations in plant morphology and molecular chemistry and are associated with a decrease in herbivore performance. These alterations are set in motion by signals generated by herbivores. Finally, a subset of induced metabolites are released into the air as volatiles and function as a beacon for foraging natural enemies searching for prey, and this is referred to as induced indirect defence. The objective of this review is to evaluate (1) which strategies plants have evolved to cope with herbivores and (2) which traits herbivores have evolved that enable them to counter these defences. The primary focus is on the induction and suppression of plant defences and the review outlines how the palette of traits that determine induction/suppression of, and resistance/susceptibility of herbivores to, plant defences can give rise to

  15. Understanding Defense Mechanisms.

    Science.gov (United States)

    Cramer, Phebe

    2015-12-01

    Understanding defense mechanisms is an important part of psychotherapy. In this article, we trace the history of the concept of defense, from its origin with Freud to current views. The issue of defense as an unconscious mechanism is examined. The question of whether defenses are pathological, as well as their relation to pathology, is discussed. The effect of psychotherapy on the use of defenses, and their relation to a therapeutic alliance is explored. A series of empirical research studies that demonstrate the functioning of defense mechanisms and that support the theory is presented. Research also shows that as part of normal development, different defenses emerge at different developmental periods, and that gender differences in defense use occur.

  16. Cattle Tick Rhipicephalus microplus-Host Interface: A Review of Resistant and Susceptible Host Responses

    Directory of Open Access Journals (Sweden)

    Ala E. Tabor

    2017-12-01

    Full Text Available Ticks are able to transmit tick-borne infectious agents to vertebrate hosts which cause major constraints to public and livestock health. The costs associated with mortality, relapse, treatments, and decreased production yields are economically significant. Ticks adapted to a hematophagous existence after the vertebrate hemostatic system evolved into a multi-layered defense system against foreign invasion (pathogens and ectoparasites, blood loss, and immune responses. Subsequently, ticks evolved by developing an ability to suppress the vertebrate host immune system with a devastating impact particularly for exotic and crossbred cattle. Host genetics defines the immune responsiveness against ticks and tick-borne pathogens. To gain an insight into the naturally acquired resistant and susceptible cattle breed against ticks, studies have been conducted comparing the incidence of tick infestation on bovine hosts from divergent genetic backgrounds. It is well-documented that purebred and crossbred Bos taurus indicus cattle are more resistant to ticks and tick-borne pathogens compared to purebred European Bos taurus taurus cattle. Genetic studies identifying Quantitative Trait Loci markers using microsatellites and SNPs have been inconsistent with very low percentages relating phenotypic variation with tick infestation. Several skin gene expression and immunological studies have been undertaken using different breeds, different samples (peripheral blood, skin with tick feeding, infestation protocols and geographic environments. Susceptible breeds were commonly found to be associated with the increased expression of toll like receptors, MHC Class II, calcium binding proteins, and complement factors with an increased presence of neutrophils in the skin following tick feeding. Resistant breeds had higher levels of T cells present in the skin prior to tick infestation and thus seem to respond to ticks more efficiently. The skin of resistant breeds also

  17. microRNA-146a promotes mycobacterial survival in macrophages through suppressing nitric oxide production.

    Science.gov (United States)

    Li, Miao; Wang, Jinli; Fang, Yimin; Gong, Sitang; Li, Meiyu; Wu, Minhao; Lai, Xiaomin; Zeng, Gucheng; Wang, Yi; Yang, Kun; Huang, Xi

    2016-03-30

    Macrophages play a crucial role in host innate anti-mycobacterial defense, which is tightly regulated by multiple factors, including microRNAs. Our previous study showed that a panel of microRNAs was markedly up-regulated in macrophages upon mycobacterial infection. Here, we investigated the biological function of miR-146a during mycobacterial infection. miR-146a expression was induced both in vitro and in vivo after Mycobacterium bovis BCG infection. The inducible miR-146a could suppress the inducible nitric oxide (NO) synthase (iNOS) expression and NO generation, thus promoting mycobacterial survival in macrophages. Inhibition of endogenous miR-146a increased NO production and mycobacterial clearance. Moreover, miR-146a attenuated the activation of nuclear factor κB and mitogen-activated protein kinases signaling pathways during BCG infection, which in turn repressed iNOS expression. Mechanistically, miR-146a directly targeted tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) at post-transcriptional level. Silencing TRAF6 decreased iNOS expression and NO production in BCG-infected macrophages, while overexpression of TRAF6 reversed miR-146a-mediated inhibition of NO production and clearance of mycobacteria. Therefore, we demonstrated a novel role of miR-146a in the modulation of host defense against mycobacterial infection by repressing NO production via targeting TRAF6, which may provide a promising therapeutic target for tuberculosis.

  18. Role of macrophages in early host resistance to respiratory Acinetobacter baumannii infection.

    Directory of Open Access Journals (Sweden)

    Hongyu Qiu

    Full Text Available Acinetobacter baumannii is an emerging bacterial pathogen that causes nosocomial pneumonia and other infections. Although it is recognized as an increasing threat to immunocompromised patients, the mechanism of host defense against A. baumannii infection remains poorly understood. In this study, we examined the potential role of macrophages in host defense against A. baumannii infection using in vitro macrophage culture and the mouse model of intranasal (i.n. infection. Large numbers of A. baumannii were taken up by alveolar macrophages in vivo as early as 4 h after i.n. inoculation. By 24 h, the infection induced significant recruitment and activation (enhanced expression of CD80, CD86 and MHC-II of macrophages into bronchoalveolar spaces. In vitro cell culture studies showed that A. baumannii were phagocytosed by J774A.1 (J774 macrophage-like cells within 10 minutes of co-incubation, and this uptake was microfilament- and microtubule-dependent. Moreover, the viability of phagocytosed bacteria dropped significantly between 24 and 48 h after co-incubation. Infection of J774 cells by A. baumannii resulted in the production of large amounts of proinflammatory cytokines and chemokines, and moderate amounts of nitric oxide (NO. Prior treatment of J774 cells with NO inhibitors significantly suppressed their bactericidal efficacy (P<0.05. Most importantly, in vivo depletion of alveolar macrophages significantly enhanced the susceptibility of mice to i.n. A. baumannii challenge (P<0.01. These results indicate that macrophages may play an important role in early host defense against A. baumannii infection through the efficient phagocytosis and killing of A. baumannii to limit initial pathogen replication and the secretion of proinflammatory cytokines and chemokines for the rapid recruitment of other innate immune cells such as neutrophils.

  19. Innate defense regulator peptide 1018 in wound healing and wound infection.

    Directory of Open Access Journals (Sweden)

    Lars Steinstraesser

    Full Text Available Innate defense regulators (IDRs are synthetic immunomodulatory versions of natural host defense peptides (HDP. IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

  20. Defense Co-Production: Collaborative National Defense

    National Research Council Canada - National Science Library

    Richardson, Robert R

    2005-01-01

    ...) and the defense industry at large. The aim of the study will be to examine the evolution of the procurement and contracting process since World War II with a qualitative and quantitative evaluation of the increasingly symbiotic...

  1. Mechanisms of plant defense against insect herbivores

    Science.gov (United States)

    War, Abdul Rashid; Paulraj, Michael Gabriel; Ahmad, Tariq; Buhroo, Abdul Ahad; Hussain, Barkat; Ignacimuthu, Savarimuthu; Sharma, Hari Chand

    2012-01-01

    Plants respond to herbivory through various morphological, biochemicals, and molecular mechanisms to counter/offset the effects of herbivore attack. The biochemical mechanisms of defense against the herbivores are wide-ranging, highly dynamic, and are mediated both by direct and indirect defenses. The defensive compounds are either produced constitutively or in response to plant damage, and affect feeding, growth, and survival of herbivores. In addition, plants also release volatile organic compounds that attract the natural enemies of the herbivores. These strategies either act independently or in conjunction with each other. However, our understanding of these defensive mechanisms is still limited. Induced resistance could be exploited as an important tool for the pest management to minimize the amounts of insecticides used for pest control. Host plant resistance to insects, particularly, induced resistance, can also be manipulated with the use of chemical elicitors of secondary metabolites, which confer resistance to insects. By understanding the mechanisms of induced resistance, we can predict the herbivores that are likely to be affected by induced responses. The elicitors of induced responses can be sprayed on crop plants to build up the natural defense system against damage caused by herbivores. The induced responses can also be engineered genetically, so that the defensive compounds are constitutively produced in plants against are challenged by the herbivory. Induced resistance can be exploited for developing crop cultivars, which readily produce the inducible response upon mild infestation, and can act as one of components of integrated pest management for sustainable crop production. PMID:22895106

  2. Dual RNA-Sequencing of Eucalyptus nitens during Phytophthora cinnamomi Challenge Reveals Pathogen and Host Factors Influencing Compatibility.

    Science.gov (United States)

    Meyer, Febé E; Shuey, Louise S; Naidoo, Sitha; Mamni, Thandekile; Berger, Dave K; Myburg, Alexander A; van den Berg, Noëlani; Naidoo, Sanushka

    2016-01-01

    Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers, and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1). Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR) genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets, and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction.

  3. Dual RNA-sequencing of Eucalyptus nitens during Phytophthora cinnamomi challenge reveals pathogen and host factors influencing compatibility

    Directory of Open Access Journals (Sweden)

    Febe Elizabeth Meyer

    2016-03-01

    Full Text Available Damage caused by Phytophthora cinnamomi Rands remains an important concern on forest tree species. The pathogen causes root and collar rot, stem cankers and dieback of various economically important Eucalyptus spp. In South Africa, susceptible cold tolerant Eucalyptus plantations have been affected by various Phytophthora spp. with P. cinnamomi considered one of the most virulent. The molecular basis of this compatible interaction is poorly understood. In this study, susceptible Eucalyptus nitens plants were stem inoculated with P. cinnamomi and tissue was harvested five days post inoculation. Dual RNA-sequencing, a technique which allows the concurrent detection of both pathogen and host transcripts during infection, was performed. Approximately 1% of the reads mapped to the draft genome of P. cinnamomi while 78% of the reads mapped to the Eucalyptus grandis genome. The highest expressed P. cinnamomi gene in planta was a putative crinkler effector (CRN1. Phylogenetic analysis indicated the high similarity of this P. cinnamomi CRN1 to that of Phytophthora infestans. Some CRN effectors are known to target host nuclei to suppress defense. In the host, over 1400 genes were significantly differentially expressed in comparison to mock inoculated trees, including suites of pathogenesis related (PR genes. In particular, a PR-9 peroxidase gene with a high similarity to a Carica papaya PR-9 ortholog previously shown to be suppressed upon infection by Phytophthora palmivora was down-regulated two-fold. This PR-9 gene may represent a cross-species effector target during P. cinnamomi infection. This study identified pathogenicity factors, potential manipulation targets and attempted host defense mechanisms activated by E. nitens that contributed to the susceptible outcome of the interaction.

  4. Comparative Analyses of Tomato yellow leaf curl virus C4 Protein-Interacting Host Proteins in Healthy and Infected Tomato Tissues

    Directory of Open Access Journals (Sweden)

    Namgyu Kim

    2016-10-01

    Full Text Available Tomato yellow leaf curl virus (TYLCV, a member of the genus Begomovirus, is one of the most important viruses of cultivated tomatoes worldwide, mainly causing yellowing and curling of leaves with stunting in plants. TYLCV causes severe problems in sub-tropical and tropical countries, as well as in Korea. However, the mechanism of TYLCV infection remains unclear, although the function of each viral component has been identified. TYLCV C4 codes for a small protein involved in various cellular functions, including symptom determination, gene silencing, viral movement, and induction of the plant defense response. In this study, through yeast-two hybrid screenings, we identified TYLCV C4-interacting host proteins from both healthy and symptom-exhibiting tomato tissues, to determine the role of TYLCV C4 proteins in the infection processes. Comparative analyses of 28 proteins from healthy tissues and 36 from infected tissues showing interactions with TYLCV C4 indicated that TYLCV C4 mainly interacts with host proteins involved in translation, ubiquitination, and plant defense, and most interacting proteins differed between the two tissues but belong to similar molecular functional categories. Four proteins—two ribosomal proteins, S-adenosyl-L-homocysteine hydrolase, and 14-3-3 family protein—were detected in both tissues. Furthermore, the identified proteins in symptom-exhibiting tissues showed greater involvement in plant defenses. Some are key regulators, such as receptor-like kinases and pathogenesis-related proteins, of plant defenses. Thus, TYLCV C4 may contribute to the suppression of host defense during TYLCV infection and be involved in ubiquitination for viral infection.

  5. Host-microbe and microbe-microbe interactions in the evolution of obligate plant parasitism.

    Science.gov (United States)

    Kemen, Ariane C; Agler, Matthew T; Kemen, Eric

    2015-06-01

    Research on obligate biotrophic plant parasites, which reproduce only on living hosts, has revealed a broad diversity of filamentous microbes that have independently acquired complex morphological structures, such as haustoria. Genome studies have also demonstrated a concerted loss of genes for metabolism and lytic enzymes, and gain of diversity of genes coding for effectors involved in host defense suppression. So far, these traits converge in all known obligate biotrophic parasites, but unexpected genome plasticity remains. This plasticity is manifested as transposable element (TE)-driven increases in genome size, observed to be associated with the diversification of virulence genes under selection pressure. Genome expansion could result from the governing of the pathogen response to ecological selection pressures, such as host or nutrient availability, or to microbial interactions, such as competition, hyperparasitism and beneficial cooperations. Expansion is balanced by alternating sexual and asexual cycles, as well as selfing and outcrossing, which operate to control transposon activity in populations. In turn, the prevalence of these balancing mechanisms seems to be correlated with external biotic factors, suggesting a complex, interconnected evolutionary network in host-pathogen-microbe interactions. Therefore, the next phase of obligate biotrophic pathogen research will need to uncover how this network, including multitrophic interactions, shapes the evolution and diversity of pathogens. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  6. Transcriptome analysis of sugar beet root maggot (Tetanops myopaeformis) genes modulated by the Beta vulgaris host.

    Science.gov (United States)

    Li, Haiyan; Smigocki, Ann C

    2018-04-01

    Sugar beet root maggot (SBRM, Tetanops myopaeformis von Röder) is a major but poorly understood insect pest of sugar beet (Beta vulgaris L.). The molecular mechanisms underlying plant defense responses are well documented, however, little information is available about complementary mechanisms for insect adaptive responses to overcome host resistance. To date, no studies have been published on SBRM gene expression profiling. Suppressive subtractive hybridization (SSH) generated more than 300 SBRM ESTs differentially expressed in the interaction of the pest with a moderately resistant (F1016) and a susceptible (F1010) sugar beet line. Blast2GO v. 3.2 search indicated that over 40% of the differentially expressed genes had known functions, primarily driven by fruit fly D. melanogaster genes. Expression patterns of 18 selected EST clones were confirmed by RT-PCR analysis. Gene Ontology (GO) analysis predicted a dominance of metabolic and catalytic genes involved in the interaction of SBRM with its host. SBRM genes functioning during development, regulation, cellular process, signaling and under stress conditions were annotated. SBRM genes that were common or unique in response to resistant or susceptible interactions with the host were identified and their possible roles in insect responses to the host are discussed. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.

  7. Host-Pathogen Interactions in Campylobacter Infections: the Host Perspective

    Science.gov (United States)

    Janssen, Riny; Krogfelt, Karen A.; Cawthraw, Shaun A.; van Pelt, Wilfrid; Wagenaar, Jaap A.; Owen, Robert J.

    2008-01-01

    Campylobacter is a major cause of acute bacterial diarrhea in humans worldwide. This study was aimed at summarizing the current understanding of host mechanisms involved in the defense against Campylobacter by evaluating data available from three sources: (i) epidemiological observations, (ii) observations of patients, and (iii) experimental observations including observations of animal models and human volunteer studies. Analysis of available data clearly indicates that an effective immune system is crucial for the host defense against Campylobacter infection. Innate, cell-mediated, and humoral immune responses are induced during Campylobacter infection, but the relative importance of these mechanisms in conferring protective immunity against reinfection is unclear. Frequent exposure to Campylobacter does lead to the induction of short-term protection against disease but most probably not against colonization. Recent progress in the development of more suitable animal models for studying Campylobacter infection has opened up possibilities to study the importance of innate and adaptive immunity during infection and in protection against reinfection. In addition, advances in genomics and proteomics technologies will enable more detailed molecular studies. Such studies combined with better integration of host and pathogen research driven by epidemiological findings may truly advance our understanding of Campylobacter infection in humans. PMID:18625685

  8. Penitentiary integral defense

    OpenAIRE

    Francisco Javier Rodríguez Román

    2012-01-01

    Penitentiary integral defense is a set of techniques designed to solve the breach of the peace that may appear in the penitentiary world. This paper studies the scope and legal framework of penitentiary self-defense. This kind of self-defense is defined by the particular characteristics of a confinement context and a very specific regulation aimed at preserving the integrity of prisoners and penitentiary staff as well as prison facilities. A technical section illustrating the main penitentiar...

  9. Suppression mental questionnaire: a preliminary study

    Directory of Open Access Journals (Sweden)

    Salvatore Settineri

    2016-08-01

    Full Text Available Authors postulate that the difference between suppression and repression, highlighted in particular by the Societè Psychanalitique de Paris, enables the development of a quantitative instrument, since suppression is a defense accessible to consciousness and therefore quantifiable like scales and questionnaires. The idea of constructing a questionnaire, included the identification of thirty variables having somehow a plausible relationship with this mechanism. The factor exploratory analysis were identified three factors, named respectly “repressive function”,  “regression to the ego service” and “rationalization”, the first of which is the closest to the theoretical construct postulated.

  10. Macrophage defense mechanisms against intracellular bacteria.

    Science.gov (United States)

    Weiss, Günter; Schaible, Ulrich E

    2015-03-01

    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. © 2015 The Authors

  11. Implementing an Integrated Network Defense Construct

    Science.gov (United States)

    2013-06-01

    largely signature based, 4 requiring prior knowledge of a threat. Second, enterprise- class network defense devices handle incredibly high speeds...to the high volume of response actions that must be performed on enterprise- class networks, very little analysis is applied to the correlation of the...examine traffic only at perimeter gateways. Some enterprise antivirus solutions provide protection at the host level, but fail to allow network

  12. Macrophage defense mechanisms against intracellular bacteria

    Science.gov (United States)

    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

  13. Mechanisms of the Innate Defense Regulator Peptide-1002 Anti-Inflammatory Activity in a Sterile Inflammation Mouse Model.

    Science.gov (United States)

    Wu, Bing Catherine; Lee, Amy Huei-Yi; Hancock, Robert E W

    2017-11-15

    Innate defense regulator (IDR) peptide-1002 is a synthetic host defense peptide derivative with strong anti-inflammatory properties. Extending previous data, IDR-1002 suppressed in vitro inflammatory responses in RAW 264.7 murine monocyte/macrophage cells challenged with the TLR4 agonist LPS and TLR2 agonists lipoteichoic acid and zymosan. To investigate the anti-inflammatory mechanisms of IDR-1002 in vivo, the PMA-induced mouse ear inflammation model was used. Topical IDR-1002 treatment successfully dampened PMA-induced ear edema, proinflammatory cytokine production, reactive oxygen and nitrogen species release, and neutrophil recruitment in the ears of CD1 mice. Advanced RNA transcriptomic analysis on the mouse ear transcriptome revealed that IDR-1002 reduced sterile inflammation by suppressing the expression of transmembrane G protein-coupled receptors (class A/1 rhodopsin-like), including receptors for chemokines, PGs, histamine, platelet activating factor, and anaphylatoxin. IDR-1002 also dampened the IFN-γ response and repressed the IFN regulatory factor 8-regulated network that controls central inflammatory pathways. This study demonstrates that IDR-1002 exhibits strong in vitro and in vivo anti-inflammatory activities, informs the underlying anti-inflammatory mechanisms, and reveals its potential as a novel therapeutic for inflammatory diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. Salmonella Populations inside Host Cells

    Directory of Open Access Journals (Sweden)

    Sónia Castanheira

    2017-10-01

    Full Text Available Bacteria of the Salmonella genus cause diseases ranging from gastroenteritis to life-threatening typhoid fever and are among the most successful intracellular pathogens known. After the invasion of the eukaryotic cell, Salmonella exhibits contrasting lifestyles with different replication rates and subcellular locations. Although Salmonella hyper-replicates in the cytosol of certain host cell types, most invading bacteria remain within vacuoles in which the pathogen proliferates at moderate rates or persists in a dormant-like state. Remarkably, these cytosolic and intra-vacuolar intracellular lifestyles are not mutually exclusive and can co-exist in the same infected host cell. The mechanisms that direct the invading bacterium to follow the cytosolic or intra-vacuolar “pathway” remain poorly understood. In vitro studies show predominance of either the cytosolic or the intra-vacuolar population depending on the host cell type invaded by the pathogen. The host and pathogen factors controlling phagosomal membrane integrity and, as consequence, the egress into the cytosol, are intensively investigated. Other aspects of major interest are the host defenses that may affect differentially the cytosolic and intra-vacuolar populations and the strategies used by the pathogen to circumvent these attacks. Here, we summarize current knowledge about these Salmonella intracellular subpopulations and discuss how they emerge during the interaction of this pathogen with the eukaryotic cell.

  15. Differential gene expression in gall midge susceptible rice genotypes revealed by suppressive subtraction hybridization (SSH) cDNA libraries and microarray analysis.

    Science.gov (United States)

    Rawat, Nidhi; Neeraja, Chiruvuri Naga; Nair, Suresh; Bentur, Jagadish S

    2012-12-01

    A major pest of rice, the Asian rice gall midge (Orseolia oryzae Wood-Mason), causes significant yield losses in the rice growing regions throughout Asia. Feeding by the larvae induces susceptible plants to produce nutritive tissue to support growth and development. In order to identify molecular signatures during compatible interactions, genome wide transcriptional profiling was performed using SSH library and microarray technology. Results revealed up-regulation of genes related to primary metabolism, nutrient relocation, cell organization and DNA synthesis. Concomitantly, defense, secondary metabolism and signaling genes were suppressed. Further, real-time PCR validation of a selected set of 20 genes, in three susceptible rice varieties (TN1, Kavya and Suraksha) during the interaction with the respective virulent gall midge biotypes, also revealed variation in gene expression in Kavya as compared to TN1 and Suraksha. These studies showed that virulent insects induced the plants to step up metabolism and transport nutrients to their feeding site and suppressed defense responses. But Kavya rice mounted an elevated defense response during early hours of virulent gall midge infestation, which was over-powered later, resulting in host plant susceptibility.

  16. Forgiveness and Defense Style

    Science.gov (United States)

    Maltby, John; Day, Liz

    2004-01-01

    Within the literature on the psychology of forgiveness, researchers have hypothesized that the 1st stage in the process of being able to forgive is the role of psychological defense. To examine such a hypothesis, the authors explored the relationship between forgiveness and defense style. The 304 respondents (151 men, 153 women) completed measures…

  17. Defense Signaling in Plants

    Indian Academy of Sciences (India)

    Self defense is the basic response of every living organism. This response is readily observed in animals because of their physical movements typically involved in that pro- cess. Being immobile, plants have evolved highly complex defense mechanisms that differ from those commonly seen in animals. Plants are able to ...

  18. Defense Mechanisms: A Bibliography.

    Science.gov (United States)

    Pedrini, D. T.; Pedrini, Bonnie C.

    This bibliography includes studies of defense mechanisms, in general, and studies of multiple mechanisms. Defense mechanisms, briefly and simply defined, are the unconscious ego defendants against unpleasure, threat, or anxiety. Sigmund Freud deserves the clinical credit for studying many mechanisms and introducing them in professional literature.…

  19. Tanscriptomic Study of the Soybean-Fusarium virguliforme Interaction Revealed a Novel Ankyrin-Repeat Containing Defense Gene, Expression of Whose during Infection Led to Enhanced Resistance to the Fungal Pathogen in Transgenic Soybean Plants.

    Science.gov (United States)

    Ngaki, Micheline N; Wang, Bing; Sahu, Binod B; Srivastava, Subodh K; Farooqi, Mohammad S; Kambakam, Sekhar; Swaminathan, Sivakumar; Bhattacharyya, Madan K

    2016-01-01

    Fusarium virguliforme causes the serious disease sudden death syndrome (SDS) in soybean. Host resistance to this pathogen is partial and is encoded by a large number of quantitative trait loci, each conditioning small effects. Breeding SDS resistance is therefore challenging and identification of single-gene encoded novel resistance mechanisms is becoming a priority to fight this devastating this fungal pathogen. In this transcriptomic study we identified a few putative soybean defense genes, expression of which is suppressed during F. virguliforme infection. The F. virguliforme infection-suppressed genes were broadly classified into four major classes. The steady state transcript levels of many of these genes were suppressed to undetectable levels immediately following F. virguliforme infection. One of these classes contains two novel genes encoding ankyrin repeat-containing proteins. Expression of one of these genes, GmARP1, during F. virguliforme infection enhances SDS resistance among the transgenic soybean plants. Our data suggest that GmARP1 is a novel defense gene and the pathogen presumably suppress its expression to establish compatible interaction.

  20. Tanscriptomic Study of the Soybean-Fusarium virguliforme Interaction Revealed a Novel Ankyrin-Repeat Containing Defense Gene, Expression of Whose during Infection Led to Enhanced Resistance to the Fungal Pathogen in Transgenic Soybean Plants.

    Directory of Open Access Journals (Sweden)

    Micheline N Ngaki

    Full Text Available Fusarium virguliforme causes the serious disease sudden death syndrome (SDS in soybean. Host resistance to this pathogen is partial and is encoded by a large number of quantitative trait loci, each conditioning small effects. Breeding SDS resistance is therefore challenging and identification of single-gene encoded novel resistance mechanisms is becoming a priority to fight this devastating this fungal pathogen. In this transcriptomic study we identified a few putative soybean defense genes, expression of which is suppressed during F. virguliforme infection. The F. virguliforme infection-suppressed genes were broadly classified into four major classes. The steady state transcript levels of many of these genes were suppressed to undetectable levels immediately following F. virguliforme infection. One of these classes contains two novel genes encoding ankyrin repeat-containing proteins. Expression of one of these genes, GmARP1, during F. virguliforme infection enhances SDS resistance among the transgenic soybean plants. Our data suggest that GmARP1 is a novel defense gene and the pathogen presumably suppress its expression to establish compatible interaction.

  1. Unfolding Green Defense

    DEFF Research Database (Denmark)

    Larsen, Kristian Knus

    2015-01-01

    to inform and support the further development of green solutions by unfolding how green technologies and green strategies have been developed and used to handle current security challenges. The report, initially, focuses on the security challenges that are being linked to green defense, namely fuel......In recent years, many states have developed and implemented green solutions for defense. Building on these initiatives NATO formulated the NATO Green Defence Framework in 2014. The framework provides a broad basis for cooperation within the Alliance on green solutions for defense. This report aims...... consumption in military operations, defense expenditure, energy security, and global climate change. The report then proceeds to introduce the NATO Green Defence Framework before exploring specific current uses of green technologies and green strategies for defense. The report concludes that a number...

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

    Science.gov (United States)

    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.

  3. Influenza A Virus-Host Protein Interactions Control Viral Pathogenesis.

    Science.gov (United States)

    Zhao, Mengmeng; Wang, Lingyan; Li, Shitao

    2017-08-01

    The influenza A virus (IAV), a member of the Orthomyxoviridae family, is a highly transmissible respiratory pathogen and represents a continued threat to global health with considerable economic and social impact. IAV is a zoonotic virus that comprises a plethora of strains with different pathogenic profiles. The different outcomes of viral pathogenesis are dependent on the engagement between the virus and the host cellular protein interaction network. The interactions may facilitate virus hijacking of host molecular machinery to fulfill the viral life cycle or trigger host immune defense to eliminate the virus. In recent years, much effort has been made to discover the virus-host protein interactions and understand the underlying mechanisms. In this paper, we review the recent advances in our understanding of IAV-host interactions and how these interactions contribute to host defense and viral pathogenesis.

  4. Plant defense against insect herbivores

    DEFF Research Database (Denmark)

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

    2013-01-01

    Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar......, defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce...

  5. Change in Coping and Defense Mechanisms across Adulthood: Longitudinal Findings in a European American Sample

    Science.gov (United States)

    Diehl, Manfred; Chui, Helena; Hay, Elizabeth L.; Lumley, Mark A.; Grühn, Daniel; Labouvie-Vief, Gisela

    2014-01-01

    This study examined longitudinal changes in coping and defense mechanisms in an age- and gender-stratified sample of 392 European American adults. Nonlinear age-related changes were found for the coping mechanisms of sublimation and suppression and the defense mechanisms of intellectualization, doubt, displacement, and regression. The change…

  6. Salicylic acid, a plant defense hormone, is specifically secreted by a molluscan herbivore.

    Directory of Open Access Journals (Sweden)

    Julia Kästner

    Full Text Available Slugs and snails are important herbivores in many ecosystems. They differ from other herbivores by their characteristic mucus trail. As the mucus is secreted at the interface between the plants and the herbivores, its chemical composition may play an essential role in plant responses to slug and snail attack. Based on our current knowledge about host-manipulation strategies employed by pathogens and insects, we hypothesized that mollusks may excrete phytohormone-like substances into their mucus. We therefore screened locomotion mucus from thirteen molluscan herbivores for the presence of the plant defense hormones jasmonic acid (JA, salicylic acid (SA and abscisic acid (ABA. We found that the locomotion mucus of one slug, Deroceras reticulatum, contained significant amounts of SA, a plant hormone that is known to induce resistance to pathogens and to suppress plant immunity against herbivores. None of the other slugs and snails contained SA or any other hormone in their locomotion mucus. When the mucus of D. reticulatum was applied to wounded leaves of A. thaliana, the promotor of the SA-responsive gene pathogenesis related 1 (PR1 was activated, demonstrating the potential of the mucus to regulate plant defenses. We discuss the potential ecological, agricultural and medical implications of this finding.

  7. Salicylic acid, a plant defense hormone, is specifically secreted by a molluscan herbivore.

    Science.gov (United States)

    Kästner, Julia; von Knorre, Dietrich; Himanshu, Himanshu; Erb, Matthias; Baldwin, Ian T; Meldau, Stefan

    2014-01-01

    Slugs and snails are important herbivores in many ecosystems. They differ from other herbivores by their characteristic mucus trail. As the mucus is secreted at the interface between the plants and the herbivores, its chemical composition may play an essential role in plant responses to slug and snail attack. Based on our current knowledge about host-manipulation strategies employed by pathogens and insects, we hypothesized that mollusks may excrete phytohormone-like substances into their mucus. We therefore screened locomotion mucus from thirteen molluscan herbivores for the presence of the plant defense hormones jasmonic acid (JA), salicylic acid (SA) and abscisic acid (ABA). We found that the locomotion mucus of one slug, Deroceras reticulatum, contained significant amounts of SA, a plant hormone that is known to induce resistance to pathogens and to suppress plant immunity against herbivores. None of the other slugs and snails contained SA or any other hormone in their locomotion mucus. When the mucus of D. reticulatum was applied to wounded leaves of A. thaliana, the promotor of the SA-responsive gene pathogenesis related 1 (PR1) was activated, demonstrating the potential of the mucus to regulate plant defenses. We discuss the potential ecological, agricultural and medical implications of this finding.

  8. Messages from the other side: parasites receive damage cues from their host plants

    OpenAIRE

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

    2016-01-01

    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 exam...

  9. Parasitoid polydnaviruses and immune interaction with secondary hosts.

    Science.gov (United States)

    Ye, Xi-Qian; Shi, Min; Huang, Jian-Hua; Chen, Xue-Xin

    2018-01-17

    Polydnaviruses (PDVs) are obligatory symbionts with parasitoid wasps. The PDV virions are produced solely in wasp (the primary host) calyx cells. They are injected into caterpillar hosts (the secondary host) during parasitoid oviposition, where they express irreplaceable actions to ensure survival and development of wasp larvae. Some of PDV gene products suppress host immune responses while others alter host growth, metabolism or endocrine system. Here, we treat new findings on PDV gene products and their action on immunity within secondary hosts. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

    Directory of Open Access Journals (Sweden)

    Go Kamoshida

    2018-02-01

    Full Text Available Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs, has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA, and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections.

  11. Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

    Science.gov (United States)

    Kamoshida, Go; Kikuchi-Ueda, Takane; Nishida, Satoshi; Tansho-Nagakawa, Shigeru; Ubagai, Tsuneyuki; Ono, Yasuo

    2018-01-01

    Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA), and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections. PMID:29467765

  12. Bordetella adenylate cyclase toxin: a swift saboteur of host defense

    Czech Academy of Sciences Publication Activity Database

    Vojtová, Jana; Kamanová, Jana; Šebo, Peter

    2006-01-01

    Roč. 9, - (2006), s. 1-7 ISSN 1369-5274 R&D Projects: GA AV ČR IAA5020406; GA MŠk 1M0506 Institutional research plan: CEZ:AV0Z50200510 Keywords : cyaa * scanning electron microscopy * cyclase toxin Subject RIV: EE - Microbiology, Virology Impact factor: 7.445, year: 2006

  13. Intestinal Enterococcus faecium Colonization Improves Host Defense during Polymicrobial Peritonitis

    NARCIS (Netherlands)

    Leendertse, Masja; Willems, Rob J. L.; Oei, G. Anneke; Florquin, Sandrine; Bonten, Marc J. M.; van der Poll, Tom

    2009-01-01

    Background. Vancomycin-resistant (VR) Enterococcus faecium is increasingly found to colonize and infect hospitalized patients. Enterococci are frequently isolated from polymicrobial infections originating from the intestines. The impact of VR E. faecium on these infections and vice versa is not

  14. Surfactant protein-D and pulmonary host defense

    Directory of Open Access Journals (Sweden)

    Crouch Erika C

    2000-08-01

    Full Text Available Abstract Surfactant protein-D (SP-D participates in the innate response to inhaled microorganisms and organic antigens, and contributes to immune and inflammatory regulation within the lung. SP-D is synthesized and secreted by alveolar and bronchiolar epithelial cells, but is also expressed by epithelial cells lining various exocrine ducts and the mucosa of the gastrointestinal and genitourinary tracts. SP-D, a collagenous calcium-dependent lectin (or collectin, binds to surface glycoconjugates expressed by a wide variety of microorganisms, and to oligosaccharides associated with the surface of various complex organic antigens. SP-D also specifically interacts with glycoconjugates and other molecules expressed on the surface of macrophages, neutrophils, and lymphocytes. In addition, SP-D binds to specific surfactant-associated lipids and can influence the organization of lipid mixtures containing phosphatidylinositol in vitro. Consistent with these diverse in vitro activities is the observation that SP-D-deficient transgenic mice show abnormal accumulations of surfactant lipids, and respond abnormally to challenge with respiratory viruses and bacterial lipopolysaccharides. The phenotype of macrophages isolated from the lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of emphysema. The expression of SP-D is increased in response to many forms of lung injury, and deficient accumulation of appropriately oligomerized SP-D might contribute to the pathogenesis of a variety of human lung diseases.

  15. Trained immunity: a memory for innate host defense

    NARCIS (Netherlands)

    Netea, M.G.; Quintin, J.; Meer, J.W.M. van der

    2011-01-01

    Immune responses in vertebrates are classically divided into innate and adaptive, with only the latter being able to build up immunological memory. However, although lacking adaptive immune responses, plants and invertebrates are protected against reinfection with pathogens, and invertebrates even

  16. Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia.

    Science.gov (United States)

    van der Windt, G J W; Hoogerwerf, J J; de Vos, A F; Florquin, S; van der Poll, T

    2010-12-01

    Klebsiella pneumoniae is a common cause of nosocomial pneumonia. Osteopontin (OPN) is a phosphorylated glycoprotein involved in inflammatory processes, some of which is mediated by CD44. The aim of this study was to determine the role of OPN during K. pneumoniae-induced pneumonia. Wild-type (WT) and OPN knockout (KO) mice were intranasally infected with 10⁴ colony forming units of K. pneumoniae, or administered Klebsiella lipopolysaccharides (LPS). In addition, recombinant OPN (rOPN) was intranasally administered to WT and CD44 KO mice. During Klebsiella pneumonia, WT mice displayed elevated pulmonary and plasma OPN levels. OPN KO and WT mice showed similar pulmonary bacterial loads 6 h after infection; thereafter, Klebsiella loads were higher in lungs of OPN KO mice and the mortality rate in this group was higher than in WT mice. Early neutrophil recruitment into the bronchoalveolar space was impaired in the absence of OPN after intrapulmonary delivery of either Klebsiella bacteria or Klebsiella LPS. Moreover, rOPN induced neutrophil migration into the bronchoalveolar space, independent from CD44. In vitro, OPN did not affect K. pneumoniae growth or neutrophil function. In conclusion, OPN levels were rapidly increased in the bronchoalveolar space during K. pneumoniae pneumonia, where OPN serves a chemotactic function towards neutrophils, thereby facilitating an effective innate immune response.

  17. Osteopontin promotes host defense during Klebsiella pneumoniae-induced pneumonia

    NARCIS (Netherlands)

    van der Windt, G. J. W.; Hoogerwerf, J. J.; de Vos, A. F.; Florquin, S.; van der Poll, T.

    2010-01-01

    Klebsiella pneumoniae is a common cause of nosocomial pneumonia. Osteopontin (OPN) is a phosphorylated glycoprotein involved in inflammatory processes, some of which is mediated by CD44. The aim of this study was to determine the role of OPN during K. pneumoniae-induced pneumonia. Wild-type (WT) and

  18. Antimicrobial peptides of buffalo and their role in host defenses

    Directory of Open Access Journals (Sweden)

    Khangembam Victoria Chanu

    2018-02-01

    Full Text Available Antimicrobial peptides (AMPs are highly conserved components of the innate immune system found among all classes of life. Buffalo (Bubalus bubalis, an important livestock for milk and meat production, is known to have a better resistance to many diseases as compared to cattle. They are found to express many AMPs such as defensins, cathelicidins, and hepcidin which play an important role in neutralizing the invading pathogens. Buffalo AMPs exhibit broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria. Similar to its natural form, synthetic analogs of buffalo AMPs are also antimicrobial against bacteria and even fungus making them a good target for the development of therapeutic antimicrobials. In addition to its antimicrobial effect, AMPs have been demonstrated to have a number of immunomodulatory functions, and their genes are responsive to infections. Further, induction of their gene expression by external factors may help in preventing infectious diseases. This review briefly discusses the AMPs of buffalo identified to date and their possible role in innate immunity.

  19. Antimicrobial peptides of buffalo and their role in host defenses.

    Science.gov (United States)

    Chanu, Khangembam Victoria; Thakuria, Dimpal; Kumar, Satish

    2018-02-01

    Antimicrobial peptides (AMPs) are highly conserved components of the innate immune system found among all classes of life. Buffalo ( Bubalus bubalis ), an important livestock for milk and meat production, is known to have a better resistance to many diseases as compared to cattle. They are found to express many AMPs such as defensins, cathelicidins, and hepcidin which play an important role in neutralizing the invading pathogens. Buffalo AMPs exhibit broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria. Similar to its natural form, synthetic analogs of buffalo AMPs are also antimicrobial against bacteria and even fungus making them a good target for the development of therapeutic antimicrobials. In addition to its antimicrobial effect, AMPs have been demonstrated to have a number of immunomodulatory functions, and their genes are responsive to infections. Further, induction of their gene expression by external factors may help in preventing infectious diseases. This review briefly discusses the AMPs of buffalo identified to date and their possible role in innate immunity.

  20. Antimicrobial peptides of buffalo and their role in host defenses

    OpenAIRE

    Khangembam Victoria Chanu; Dimpal Thakuria; Satish Kumar

    2018-01-01

    Antimicrobial peptides (AMPs) are highly conserved components of the innate immune system found among all classes of life. Buffalo (Bubalus bubalis), an important livestock for milk and meat production, is known to have a better resistance to many diseases as compared to cattle. They are found to express many AMPs such as defensins, cathelicidins, and hepcidin which play an important role in neutralizing the invading pathogens. Buffalo AMPs exhibit broad-spectrum antimicrobial activity agains...

  1. Aeromonas salmonicida type III secretion system-effectors-mediated immune suppression in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Origgi, F C; Benedicenti, O; Segner, H; Sattler, U; Wahli, T; Frey, J

    2017-01-01

    Aeromonas salmonicida subsp. salmonicida, the etiologic agent of furunculosis, is a major pathogen in aquaculture. Together with other pathogens, it is characterized by the presence of a type 3 secretion system (T3SS). The T3SS is the main virulence mechanism of A. salmonicida. It is used by the bacterium to secrete and translocate several toxins and effector proteins into the host cell. Some of these factors have a detrimental impact on the integrity of the cell cytoskeleton, likely contributing to impair phagocytosis. Furthermore, it has been suggested that effectors of the T3SS are able to modulate the host's immune response. Here we present the first partial characterization of the immune response in rainbow trout (Oncorhynchus mykiss) infected with distinct strains of A. salmonicida either carrying (i) a fully functional T3SS or (ii) a functionally impaired T3SS or (iii) devoid of T3SS ("cured" strain). Infection with an A. salmonicida strain either carrying a fully functional or a secretion-impaired T3SS was associated with a strong and persistent immune suppression. However, the infection appeared to be fatal only in the presence of a fully functional T3SS. In contrast, the absence of T3SS was neither associated with immune suppression nor fish death. These findings suggest that the T3SS and T3SS-delivered effector molecules and toxins of A. salmonicida do not only impair the host cells' cytoskeleton thus damaging cell physiology and phagocytosis, but also heavily affect the transcription of critical immune mediators including the shut-down of important warning signals to recognize infection and induce immune defense. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Defense Mechanisms in Adolescence.

    Science.gov (United States)

    Cramer, Phebe

    1979-01-01

    Results showed that by ninth or tenth grade, males begin to externalize conflict while females tend to deal with conflict internally. This differentiation of defense choice by sex is clearly established by the last two years of high school. (JMB)

  3. Cruise Missile Defense

    National Research Council Canada - National Science Library

    Hichkad, Ravi R; Bolkcom, Christopher

    2004-01-01

    Congress has expressed interest in cruise missile defense for years. Cruise missiles (CMs) are essentially unmanned attack aircraft -- vehicles composed of an airframe, propulsion system, guidance system, and weapons payload...

  4. Cruise Missile Defense

    National Research Council Canada - National Science Library

    Hichkad, Ravi R; Bolkcom, Christopher

    2005-01-01

    Congress has expressed interest in cruise missile defense for years. Cruise missiles (CMs) are essentially unmanned attack aircraft -- vehicles composed of an airframe, propulsion system, guidance system, and weapons payload...

  5. 76 FR 72391 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Science.gov (United States)

    2011-11-23

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID DOD-2011-OS-0055] Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Revised Defense Logistics Agency...

  6. 76 FR 28960 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Science.gov (United States)

    2011-05-19

    ... DEPARTMENT OF DEFENSE Office of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of Defense. ACTION: Notice of Closed Meeting. SUMMARY: Pursuant to the...

  7. 75 FR 76423 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Science.gov (United States)

    2010-12-08

    ... DEPARTMENT OF DEFENSE Office of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of Defense. ACTION: Notice of Closed Meeting. SUMMARY: Pursuant to the...

  8. Growth hormone suppression test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003376.htm Growth hormone suppression test To use the sharing features on this page, please enable JavaScript. The growth hormone suppression test determines whether growth hormone production is ...

  9. Bacterial endophytes from wild maize suppress Fusarium graminearum in modern maize and inhibit mycotoxin accumulation

    Directory of Open Access Journals (Sweden)

    Walaa Kamel Mousa

    2015-10-01

    Full Text Available Wild maize (teosinte has been reported to be less susceptible to pests than their modern maize (corn relatives. Endophytes, defined as microbes that inhabit plants without causing disease, are known for their ability to antagonize plant pests and pathogens. We hypothesized that the wild relatives of modern maize may host endophytes that combat pathogens. Fusarium graminearum is the fungus that causes Gibberella Ear Rot (GER in modern maize and produces the mycotoxin, deoxynivalenol (DON. In this study, 215 bacterial endophytes, previously isolated from diverse maize genotypes including wild teosintes, traditional landraces and modern varieties, were tested for their ability to antagonize F. graminearum in vitro. Candidate endophytes were then tested for their ability to suppress GER in modern maize in independent greenhouse trials. The results revealed that three candidate endophytes derived from wild teosintes were most potent in suppressing F. graminearum in vitro and GER in a modern maize hybrid. These wild teosinte endophytes could suppress a broad spectrum of fungal pathogens of modern crops in vitro. The teosinte endophytes also suppressed DON mycotoxin during storage to below acceptable safety threshold levels. A fourth, less robust anti-fungal strain was isolated from a modern maize hybrid. Three of the anti-fungal endophytes were predicted to be Paenibacillus polymyxa, along with one strain of Citrobacter. Microscopy studies suggested a fungicidal mode of action by all four strains. Molecular and biochemical studies showed that the P. polymyxa strains produced the previously characterized anti-Fusarium compound, fusaricidin. Our results suggest that the wild relatives of modern crops may serve as a valuable reservoir for endophytes in the ongoing fight against serious threats to modern agriculture. We discuss the possible impact of crop evolution and domestication on endophytes in the context of plant defense.

  10. Reconstruction of the evolution of microbial defense systems.

    Science.gov (United States)

    Puigbò, Pere; Makarova, Kira S; Kristensen, David M; Wolf, Yuri I; Koonin, Eugene V

    2017-04-04

    Evolution of bacterial and archaeal genomes is a highly dynamic process that involves intensive loss of genes as well as gene gain via horizontal transfer, with a lesser contribution from gene duplication. The rates of these processes can be estimated by comparing genomes that are linked by an evolutionary tree. These estimated rates of genome dynamics events substantially differ for different functional classes of genes. The genes involved in defense against viruses and other invading DNA are among those that are gained and lost at the highest rates. We employed a stochastic birth-and-death model to obtain maximum likelihood estimates of the rates of gain and loss of defense genes in 35 groups of closely related bacterial genomes and one group of archaeal genomes. We find that on average, the defense genes experience 1.4 fold higher flux than the rest of microbial genes. This excessive flux of defense genes over the genomic mean is consistent across diverse microbial groups. The few exceptions include intracellular parasites with small, degraded genomes that possess few defense systems which are more stable than in other microbes. Generally, defense genes follow the previously established pattern of genome dynamics, with gene family loss being about 3 times more common than gain and an order of magnitude more common than expansion or contraction of gene families. Case by case analysis of the evolutionary dynamics of defense genes indicates frequent multiple events in the same locus and widespread involvement of mobile elements in the gain and loss of defense genes. Evolution of microbial defense systems is highly dynamic but, notwithstanding the host-parasite arms race, generally follows the same trends that have been established for the rest of the genes. Apart from the paucity and the low flux of defense genes in parasitic bacteria with deteriorating genomes, there is no clear connection between the evolutionary regime of defense systems and microbial life style.

  11. Hibiscus chlorotic ringspot virus coat protein upregulates sulfur metabolism genes for enhanced pathogen defense.

    Science.gov (United States)

    Gao, Ruimin; Ng, Florence Kai Lin; Liu, Peng; Wong, Sek-Man

    2012-12-01

    In both Hibiscus chlorotic ringspot virus (HCRSV)-infected and HCRSV coat protein (CP) agroinfiltrated plant leaves, we showed that sulfur metabolism pathway related genes-namely, sulfite oxidase (SO), sulfite reductase, and adenosine 5'-phosphosulfate kinase-were upregulated. It led us to examine a plausible relationship between sulfur-enhanced resistance (SED) and HCRSV infection. We broadened an established method to include different concentrations of sulfur (0S, 1S, 2S, and 3S) to correlate them to symptom development of HCRSV-infected plants. We treated plants with glutathione and its inhibitor to verify the SED effect. Disease resistance was induced through elevated glutathione contents during HCRSV infection. The upregulation of SO was related to suppression of symptom development induced by sulfur treatment. In this study, we established that HCRSV-CP interacts with SO which, in turn, triggers SED and leads to enhanced plant resistance. Thus, we have discovered a new function of SO in the SED pathway. This is the first report to demonstrate that the interaction of a viral protein and host protein trigger SED in plants. It will be interesting if such interaction applies generally to other host-pathogen interactions that will lead to enhanced pathogen defense.

  12. Activation of intestinal epithelial Stat3 orchestrates tissue defense during gastrointestinal infection.

    Directory of Open Access Journals (Sweden)

    Nadine Wittkopf

    Full Text Available Gastrointestinal infections with EHEC and EPEC are responsible for outbreaks of diarrheal diseases and represent a global health problem. Innate first-line-defense mechanisms such as production of mucus and antimicrobial peptides by intestinal epithelial cells are of utmost importance for host control of gastrointestinal infections. For the first time, we directly demonstrate a critical role for Stat3 activation in intestinal epithelial cells upon infection of mice with Citrobacter rodentium - a murine pathogen that mimics human infections with attaching and effacing Escherichia coli. C. rodentium induced transcription of IL-6 and IL-22 in gut samples of mice and was associated with activation of the transcription factor Stat3 in intestinal epithelial cells. C. rodentium infection induced expression of several antimicrobial peptides such as RegIIIγ and Pla2g2a in the intestine which was critically dependent on Stat3 activation. Consequently, mice with specific deletion of Stat3 in intestinal epithelial cells showed increased susceptibility to C. rodentium infection as indicated by high bacterial load, severe gut inflammation, pronounced intestinal epithelial cell death and dissemination of bacteria to distant organs. Together, our data implicate an essential role for Stat3 activation in intestinal epithelial cells during C. rodentium infection. Stat3 concerts the host response to bacterial infection by controlling bacterial growth and suppression of apoptosis to maintain intestinal epithelial barrier function.

  13. A Small Cysteine-Rich Protein from the Asian Soybean Rust Fungus, Phakopsora pachyrhizi, Suppresses Plant Immunity.

    Directory of Open Access Journals (Sweden)

    Mingsheng Qi

    2016-09-01

    Full Text Available The Asian soybean rust fungus, Phakopsora pachyrhizi, is an obligate biotrophic pathogen causing severe soybean disease epidemics. Molecular mechanisms by which P. pachyrhizi and other rust fungi interact with their host plants are poorly understood. The genomes of all rust fungi encode many small, secreted cysteine-rich proteins (SSCRP. While these proteins are thought to function within the host, their roles are completely unknown. Here, we present the characterization of P. pachyrhizi effector candidate 23 (PpEC23, a SSCRP that we show to suppress plant immunity. Furthermore, we show that PpEC23 interacts with soybean transcription factor GmSPL12l and that soybean plants in which GmSPL12l is silenced have constitutively active immunity, thereby identifying GmSPL12l as a negative regulator of soybean defenses. Collectively, our data present evidence for a virulence function of a rust SSCRP and suggest that PpEC23 is able to suppress soybean immune responses and physically interact with soybean transcription factor GmSPL12l, a negative immune regulator.

  14. A Small Cysteine-Rich Protein from the Asian Soybean Rust Fungus, Phakopsora pachyrhizi, Suppresses Plant Immunity.

    Science.gov (United States)

    Qi, Mingsheng; Link, Tobias I; Müller, Manuel; Hirschburger, Daniela; Pudake, Ramesh N; Pedley, Kerry F; Braun, Edward; Voegele, Ralf T; Baum, Thomas J; Whitham, Steven A

    2016-09-01

    The Asian soybean rust fungus, Phakopsora pachyrhizi, is an obligate biotrophic pathogen causing severe soybean disease epidemics. Molecular mechanisms by which P. pachyrhizi and other rust fungi interact with their host plants are poorly understood. The genomes of all rust fungi encode many small, secreted cysteine-rich proteins (SSCRP). While these proteins are thought to function within the host, their roles are completely unknown. Here, we present the characterization of P. pachyrhizi effector candidate 23 (PpEC23), a SSCRP that we show to suppress plant immunity. Furthermore, we show that PpEC23 interacts with soybean transcription factor GmSPL12l and that soybean plants in which GmSPL12l is silenced have constitutively active immunity, thereby identifying GmSPL12l as a negative regulator of soybean defenses. Collectively, our data present evidence for a virulence function of a rust SSCRP and suggest that PpEC23 is able to suppress soybean immune responses and physically interact with soybean transcription factor GmSPL12l, a negative immune regulator.

  15. Regulatory T Cells and Host Anti-CML Responses

    National Research Council Canada - National Science Library

    Wong, Jr, K. K

    2008-01-01

    CD4+CD25+FoxP-3+ regulatory T-cells (Tregs) suppress immune responses to "self" antigens, but also have been shown to suppress host anti-tumor responses in several human malignancies, including breast, gastrointestinal, and ovarian cancer...

  16. Pteromalus puparum venom impairs host cellular immune responses by decreasing expression of its scavenger receptor gene

    Science.gov (United States)

    Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Although there is a rich literature on these systems, parasitoid immune-disabling mechanisms have not been fully elucidated. Here we ...

  17. Spatiotemporal heterogeneity of tomato induced defense responses affects spider mite performance and behavior.

    Science.gov (United States)

    Schimmel, Bernardus C J; Ataide, Livia M S; Kant, Merijn R

    2017-10-03

    When feeding from tomato (Solanum lycopersicum), the generalist spider mite Tetranychus urticae induces jasmonate (JA)- and salicylate (SA)-regulated defense responses that hamper its performance. The related T. evansi, a Solanaceae-specialist, suppresses these defenses, thereby upholding a high performance. On a shared leaf, T. urticae can be facilitated by T. evansi, likely via suppression of defenses by the latter. Yet, when infesting the same plant, T. evansi outcompetes T. urticae. Recently, we found that T. evansi intensifies suppression of defenses locally, i.e., at its feeding site, after T. urticae mites were introduced onto adjacent leaf tissue. This hyper-suppression is paralleled by an increased oviposition rate of T. evansi, probably promoting its competitive population growth. Here we present additional data that not only provide insight into the spatiotemporal dynamics of defense induction and suppression by mites, but that also suggest T. evansi to manipulate more than JA and SA defenses alone.

  18. Dynamics of defense responses and cell fate change during Arabidopsis-Pseudomonas syringae interactions.

    Directory of Open Access Journals (Sweden)

    Safae Hamdoun

    Full Text Available Plant-pathogen interactions involve sophisticated action and counteraction strategies from both parties. Plants can recognize pathogen derived molecules, such as conserved pathogen associated molecular patterns (PAMPs and effector proteins, and subsequently activate PAMP-triggered immunity (PTI and effector-triggered immunity (ETI, respectively. However, pathogens can evade such recognitions and suppress host immunity with effectors, causing effector-triggered susceptibility (ETS. The differences among PTI, ETS, and ETI have not been completely understood. Toward a better understanding of PTI, ETS, and ETI, we systematically examined various defense-related phenotypes of Arabidopsis infected with different Pseudomonas syringae pv. maculicola ES4326 strains, using the virulence strain DG3 to induce ETS, the avirulence strain DG34 that expresses avrRpm1 (recognized by the resistance protein RPM1 to induce ETI, and HrcC(- that lacks the type three secretion system to activate PTI. We found that plants infected with different strains displayed dynamic differences in the accumulation of the defense signaling molecule salicylic acid, expression of the defense marker gene PR1, cell death formation, and accumulation/localization of the reactive oxygen species, H2O2. The differences between PTI, ETS, and ETI are dependent on the doses of the strains used. These data support the quantitative nature of PTI, ETS, and ETI and they also reveal qualitative differences between PTI, ETS, and ETI. Interestingly, we observed the induction of large cells in the infected leaves, most obviously with HrcC(- at later infection stages. The enlarged cells have increased DNA content, suggesting a possible activation of endoreplication. Consistent with strong induction of abnormal cell growth by HrcC(-, we found that the PTI elicitor flg22 also activates abnormal cell growth, depending on a functional flg22-receptor FLS2. Thus, our study has revealed a comprehensive

  19. RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense

    Directory of Open Access Journals (Sweden)

    Karin Moelling

    2017-09-01

    Full Text Available Retroviral infections are ‘mini-symbiotic’ events supplying recipient cells with sequences for viral replication, including the reverse transcriptase (RT and ribonuclease H (RNase H. These proteins and other viral or cellular sequences can provide novel cellular functions including immune defense mechanisms. Their high error rate renders RT-RNases H drivers of evolutionary innovation. Integrated retroviruses and the related transposable elements (TEs have existed for at least 150 million years, constitute up to 80% of eukaryotic genomes and are also present in prokaryotes. Endogenous retroviruses regulate host genes, have provided novel genes including the syncytins that mediate maternal-fetal immune tolerance and can be experimentally rendered infectious again. The RT and the RNase H are among the most ancient and abundant protein folds. RNases H may have evolved from ribozymes, related to viroids, early in the RNA world, forming ribosomes, RNA replicases and polymerases. Basic RNA-binding peptides enhance ribozyme catalysis. RT and ribozymes or RNases H are present today in bacterial group II introns, the precedents of TEs. Thousands of unique RTs and RNases H are present in eukaryotes, bacteria, and viruses. These enzymes mediate viral and cellular replication and antiviral defense in eukaryotes and prokaryotes, splicing, R-loop resolvation, DNA repair. RNase H-like activities are also required for the activity of small regulatory RNAs. The retroviral replication components share striking similarities with the RNA-induced silencing complex (RISC, the prokaryotic CRISPR-Cas machinery, eukaryotic V(DJ recombination and interferon systems. Viruses supply antiviral defense tools to cellular organisms. TEs are the evolutionary origin of siRNA and miRNA genes that, through RISC, counteract detrimental activities of TEs and chromosomal instability. Moreover, piRNAs, implicated in transgenerational inheritance, suppress TEs in germ cells. Thus

  20. RNase H As Gene Modifier, Driver of Evolution and Antiviral Defense.

    Science.gov (United States)

    Moelling, Karin; Broecker, Felix; Russo, Giancarlo; Sunagawa, Shinichi

    2017-01-01

    Retroviral infections are 'mini-symbiotic' events supplying recipient cells with sequences for viral replication, including the reverse transcriptase (RT) and ribonuclease H (RNase H). These proteins and other viral or cellular sequences can provide novel cellular functions including immune defense mechanisms. Their high error rate renders RT-RNases H drivers of evolutionary innovation. Integrated retroviruses and the related transposable elements (TEs) have existed for at least 150 million years, constitute up to 80% of eukaryotic genomes and are also present in prokaryotes. Endogenous retroviruses regulate host genes, have provided novel genes including the syncytins that mediate maternal-fetal immune tolerance and can be experimentally rendered infectious again. The RT and the RNase H are among the most ancient and abundant protein folds. RNases H may have evolved from ribozymes, related to viroids, early in the RNA world, forming ribosomes, RNA replicases and polymerases. Basic RNA-binding peptides enhance ribozyme catalysis. RT and ribozymes or RNases H are present today in bacterial group II introns, the precedents of TEs. Thousands of unique RTs and RNases H are present in eukaryotes, bacteria, and viruses. These enzymes mediate viral and cellular replication and antiviral defense in eukaryotes and prokaryotes, splicing, R-loop resolvation, DNA repair. RNase H-like activities are also required for the activity of small regulatory RNAs. The retroviral replication components share striking similarities with the RNA-induced silencing complex (RISC), the prokaryotic CRISPR-Cas machinery, eukaryotic V(D)J recombination and interferon systems. Viruses supply antiviral defense tools to cellular organisms. TEs are the evolutionary origin of siRNA and miRNA genes that, through RISC, counteract detrimental activities of TEs and chromosomal instability. Moreover, piRNAs, implicated in transgenerational inheritance, suppress TEs in germ cells. Thus, virtually all known

  1. Defense mechanisms of hepatocytes against Burkholderia pseudomallei

    Directory of Open Access Journals (Sweden)

    Antje eBast

    2012-01-01

    Full Text Available The gram-negative facultative intracellular rod Burkholderia pseudomallei causes melioidosis, an infectious disease with a wide range of clinical presentations. Among the observed visceral abscesses, the liver is commonly affected. However, neither this organotropism of B. pseudomallei nor local hepatic defense mechanisms have been thoroughly investigated so far. Own previous studies using electron microscopy of the murine liver after systemic infection of mice indicated that hepatocytes might be capable of killing B. pseudomallei. Therefore, the aim of this study was to further elucidate the interaction of B. pseudomallei with these cells and to analyse the role of hepatocytes in anti-B. pseudomallei host defense. In vitro studies using the human hepatocyte cell line HepG2 revealed that B. pseudomallei can invade these cells. Subsequently, B. pseudomallei is able to escape from the vacuole, to replicate within the cytosol of HepG2 cells involving its type 3 and type 6 secretion systems, and to induce actin tail formation. Furthermore, stimulation of HepG2 cells showed that IFNgamma can restrict growth of B. pseudomallei in the early and late phase of infection whereas the combination of IFNgamma, IL-1beta and TNFalpha is required for the maximal antibacterial activity. This anti-B. pseudomallei defense of HepG2 cells did not seem to be mediated by iNOS-derived nitric oxide or NADPH oxidase-derived superoxide. In summary, this is the first study describing B. pseudomallei intracellular life cycle characteristics in hepatocytes and showing that IFNgamma-mediated, but nitric oxide- and reactive oxygen species-independent, effector mechanisms are important in anti-B. pseudomallei host defense of hepatocytes.

  2. Glucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M

    Science.gov (United States)

    Miyata, Masanori; Lee, Ji-Yun; Susuki-Miyata, Seiko; Wang, Wenzhuo Y.; Xu, Haidong; Kai, Hirofumi; Kobayashi, Koichi S.; Flavell, Richard A.; Li, Jian-Dong

    2015-01-01

    Glucocorticoids are among the most commonly used anti-inflammatory agents. Despite the enormous efforts in elucidating the glucocorticoid-mediated anti-inflammatory actions, how glucocorticoids tightly control overactive inflammatory response is not fully understood. Here we show that glucocorticoids suppress bacteria-induced inflammation by enhancing IRAK-M, a central negative regulator of Toll-like receptor signalling. The ability of glucocorticoids to suppress pulmonary inflammation induced by non-typeable Haemophilus influenzae is significantly attenuated in IRAK-M-deficient mice. Glucocorticoids improve the survival rate after a lethal non-typeable Haemophilus influenzae infection in wild-type mice, but not in IRAK-M-deficient mice. Moreover, we show that glucocorticoids and non-typeable Haemophilus influenzae synergistically upregulate IRAK-M expression via mutually and synergistically enhancing p65 and glucocorticoid receptor binding to the IRAK-M promoter. Together, our studies unveil a mechanism by which glucocorticoids tightly control the inflammatory response and host defense via the induction of IRAK-M and may lead to further development of anti-inflammatory therapeutic strategies. PMID:25585690

  3. Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.

    Directory of Open Access Journals (Sweden)

    Sammeta V Raju

    Full Text Available Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR, a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B adenosine receptor (A(2BAR, largely abolished the adenosine-stimulated chloride transport, suggesting that A(2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.

  4. Glucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M.

    Science.gov (United States)

    Miyata, Masanori; Lee, Ji-Yun; Susuki-Miyata, Seiko; Wang, Wenzhuo Y; Xu, Haidong; Kai, Hirofumi; Kobayashi, Koichi S; Flavell, Richard A; Li, Jian-Dong

    2015-01-14

    Glucocorticoids are among the most commonly used anti-inflammatory agents. Despite the enormous efforts in elucidating the glucocorticoid-mediated anti-inflammatory actions, how glucocorticoids tightly control overactive inflammatory response is not fully understood. Here we show that glucocorticoids suppress bacteria-induced inflammation by enhancing IRAK-M, a central negative regulator of Toll-like receptor signalling. The ability of glucocorticoids to suppress pulmonary inflammation induced by non-typeable Haemophilus influenzae is significantly attenuated in IRAK-M-deficient mice. Glucocorticoids improve the survival rate after a lethal non-typeable Haemophilus influenzae infection in wild-type mice, but not in IRAK-M-deficient mice. Moreover, we show that glucocorticoids and non-typeable Haemophilus influenzae synergistically upregulate IRAK-M expression via mutually and synergistically enhancing p65 and glucocorticoid receptor binding to the IRAK-M promoter. Together, our studies unveil a mechanism by which glucocorticoids tightly control the inflammatory response and host defense via the induction of IRAK-M and may lead to further development of anti-inflammatory therapeutic strategies.

  5. The paradox of chronic neuroinflammation, systemic immune suppression, autoimmunity after traumatic chronic spinal cord injury.

    Science.gov (United States)

    Schwab, Jan M; Zhang, Yi; Kopp, Marcel A; Brommer, Benedikt; Popovich, Phillip G

    2014-08-01

    During the transition from acute to chronic stages of recovery after spinal cord injury (SCI), there is an evolving state of immunologic dysfunction that exacerbates the problems associated with the more clinically obvious neurologic deficits. Since injury directly affects cells embedded within the "immune privileged/specialized" milieu of the spinal cord, maladaptive or inefficient responses are likely to occur. Collectively, these responses qualify as part of the continuum of "SCI disease" and are important therapeutic targets to improve neural repair and neurological outcome. Generic immune suppressive therapies have been largely unsuccessful, mostly because inflammation and immunity exert both beneficial (plasticity enhancing) and detrimental (e.g. glia- and neurodegenerative; secondary damage) effects and these functions change over time. Moreover, "compartimentalized" investigations, limited to only intraspinal inflammation and associated cellular or molecular changes in the spinal cord, neglect the reality that the structure and function of the CNS are influenced by systemic immune challenges and that the immune system is 'hardwired' into the nervous system. Here, we consider this interplay during the progression from acute to chronic SCI. Specifically, we survey impaired/non-resolving intraspinal inflammation and the paradox of systemic inflammatory responses in the context of ongoing chronic immune suppression and autoimmunity. The concepts of systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS) and "neurogenic" spinal cord injury-induced immune depression syndrome (SCI-IDS) are discussed as determinants of impaired "host-defense" and trauma-induced autoimmunity. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Suppression of Plant Immune Responses by the Pseudomonas savastanoi pv. savastanoi NCPPB 3335 Type III Effector Tyrosine Phosphatases HopAO1 and HopAO2

    Directory of Open Access Journals (Sweden)

    María Pilar Castañeda-Ojeda

    2017-05-01

    Full Text Available The effector repertoire of the olive pathogen P. savastanoi pv. savastanoi NCPPB 3335 includes two members of the HopAO effector family, one of the most diverse T3E families of the P. syringae complex. The study described here explores the phylogeny of these dissimilar members, HopAO1 and HopAO2, among the complex and reveals their activities as immune defense suppressors. Although HopAO1 is predominantly encoded by phylogroup 3 strains isolated from woody organs of woody hosts, both HopAO1 and HopAO2 are phylogenetically clustered according to the woody/herbaceous nature of their host of isolation, suggesting host specialization of the HopAO family across the P. syringae complex. HopAO1 and HopAO2 translocate into plant cells and show hrpL-dependent expression, which allows their classification as actively deployed type III effectors. Our data also show that HopAO1 and HopAO2 possess phosphatase activity, a hallmark of the members of this family. Both of them exert an inhibitory effect on early plant defense responses, such as ROS production and callose deposition, and are able to suppress ETI responses induced by the effectorless polymutant of P. syringae pv. tomato DC3000 (DC3000D28E in Nicotiana. Moreover, we demonstrate that a ΔhopAO1 mutant of P. savastanoi NCPBB 3335 exhibits a reduced fitness and virulence in olive plants, which supports the relevance of this effector during the interaction of this strain with its host plants. This work contributes to the field with the first report regarding functional analysis of HopAO homologs encoded by P. syringae or P. savastanoi strains isolated from woody hosts.

  7. Suppression of Plant Immune Responses by the Pseudomonas savastanoi pv. savastanoi NCPPB 3335 Type III Effector Tyrosine Phosphatases HopAO1 and HopAO2

    Science.gov (United States)

    Castañeda-Ojeda, María Pilar; Moreno-Pérez, Alba; Ramos, Cayo; López-Solanilla, Emilia

    2017-01-01

    The effector repertoire of the olive pathogen P. savastanoi pv. savastanoi NCPPB 3335 includes two members of the HopAO effector family, one of the most diverse T3E families of the P. syringae complex. The study described here explores the phylogeny of these dissimilar members, HopAO1 and HopAO2, among the complex and reveals their activities as immune defense suppressors. Although HopAO1 is predominantly encoded by phylogroup 3 strains isolated from woody organs of woody hosts, both HopAO1 and HopAO2 are phylogenetically clustered according to the woody/herbaceous nature of their host of isolation, suggesting host specialization of the HopAO family across the P. syringae complex. HopAO1 and HopAO2 translocate into plant cells and show hrpL-dependent expression, which allows their classification as actively deployed type III effectors. Our data also show that HopAO1 and HopAO2 possess phosphatase activity, a hallmark of the members of this family. Both of them exert an inhibitory effect on early plant defense responses, such as ROS production and callose deposition, and are able to suppress ETI responses induced by the effectorless polymutant of P. syringae pv. tomato DC3000 (DC3000D28E) in Nicotiana. Moreover, we demonstrate that a ΔhopAO1 mutant of P. savastanoi NCPBB 3335 exhibits a reduced fitness and virulence in olive plants, which supports the relevance of this effector during the interaction of this strain with its host plants. This work contributes to the field with the first report regarding functional analysis of HopAO homologs encoded by P. syringae or P. savastanoi strains isolated from woody hosts. PMID:28529516

  8. Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi

    NARCIS (Netherlands)

    Buffen, Kathrin; Oosting, Marije; Li, Yang; Kanneganti, Thirumala-Devi; Netea, Mihai G.; Joosten, Leo A. B.

    Inhibition of autophagy increases the severity of murine Lyme arthritis and human adaptive immune responses against B. burgdorferi. We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known

  9. Acrolein exposure suppresses antigen-induced pulmonary inflammation

    Science.gov (United States)

    2013-01-01

    Background Adverse health effects of tobacco smoke arise partly from its influence on innate and adaptive immune responses, leading to impaired innate immunity and host defense. The impact of smoking on allergic asthma remains unclear, with various reports demonstrating that cigarette smoke enhances asthma development but can also suppress allergic airway inflammation. Based on our previous findings that immunosuppressive effects of smoking may be largely attributed to one of its main reactive electrophiles, acrolein, we explored the impact of acrolein exposure in a mouse model of ovalbumin (OVA)-induced allergic asthma. Methods C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection with the adjuvant aluminum hydroxide on days 0 and 7, and challenged with aerosolized OVA on days 14–16. In some cases, mice were also exposed to 5 ppm acrolein vapor for 6 hrs/day on days 14–17. Lung tissues or brochoalveolar lavage fluids (BALF) were collected either 6 hrs after a single initial OVA challenge and/or acrolein exposure on day 14 or 48 hrs after the last OVA challenge, on day 18. Inflammatory cells and Th1/Th2 cytokine levels were measured in BALF, and lung tissue samples were collected for analysis of mucus and Th1/Th2 cytokine expression, determination of protein alkylation, cellular thiol status and transcription factor activity. Results Exposure to acrolein following OVA challenge of OVA-sensitized mice resulted in markedly attenuated allergic airway inflammation, demonstrated by decreased inflammatory cell infiltrates, mucus hyperplasia and Th2 cytokines. Acrolein exposure rapidly depleted lung tissue glutathione (GSH) levels, and induced activation of the Nrf2 pathway, indicated by accumulation of Nrf2, increased alkylation of Keap1, and induction of Nrf2-target genes such as HO-1. Additionally, analysis of inflammatory signaling pathways showed suppressed activation of NF-κB and marginally reduced activation of JNK in acrolein

  10. Mosquito immune defenses against Plasmodium infection.

    Science.gov (United States)

    Cirimotich, Chris M; Dong, Yuemei; Garver, Lindsey S; Sim, Shuzhen; Dimopoulos, George

    2010-04-01

    The causative agent of malaria, Plasmodium, has to undergo complex developmental transitions and survive attacks from the mosquito's innate immune system to achieve transmission from one host to another through the vector. Here we discuss recent findings on the role of the mosquito's innate immune signaling pathways in preventing infection by the Plasmodium parasite, the identification and mechanistic description of novel anti-parasite molecules, the role that natural bacteria harbored in the mosquito midgut might play in this immune defense and the crucial parasite and vector molecules that mediate midgut infection.

  11. Baculovirus F-Box Protein LEF-7 Modifies the Host DNA Damage Response To Enhance Virus Multiplication

    Science.gov (United States)

    Mitchell, Jonathan K.; Byers, Nathaniel M.

    2013-01-01

    The DNA damage response (DDR) of a host organism represents an effective antiviral defense that is frequently manipulated and exploited by viruses to promote multiplication. We report here that the large DNA baculoviruses, which require host DDR activation for optimal replication, encode a conserved replication factor, LEF-7, that manipulates the DDR via a novel mechanism. LEF-7 suppresses DDR-induced accumulation of phosphorylated host histone variant H2AX (γ-H2AX), a critical regulator of the DDR. LEF-7 was necessary and sufficient to block γ-H2AX accumulation caused by baculovirus infection or DNA damage induced by means of pharmacological agents. Deletion of LEF-7 from the baculovirus genome allowed γ-H2AX accumulation during virus DNA synthesis and impaired both very late viral gene expression and production of infectious progeny. Thus, LEF-7 is essential for efficient baculovirus replication. We determined that LEF-7 is a nuclear F-box protein that interacts with host S-phase kinase-associated protein 1 (SKP1), suggesting that LEF-7 acts as a substrate recognition component of SKP1/Cullin/F-box (SCF) complexes for targeted protein polyubiquitination. Site-directed mutagenesis demonstrated that LEF-7's N-terminal F-box is necessary for γ-H2AX repression and Autographa californica multiple nucleopolyhedrovirus (AcMNPV) replication events. We concluded that LEF-7 expedites virus replication most likely by selective manipulation of one or more host factors regulating the DDR, including γ-H2AX. Thus, our findings indicate that baculoviruses utilize a unique strategy among viruses for hijacking the host DDR by using a newly recognized F-box protein. PMID:24027328

  12. Proteomic Characterization of Host Response to Yersinia pestis

    Energy Technology Data Exchange (ETDEWEB)

    Chromy, B; Perkins, J; Heidbrink, J; Gonzales, A; Murhpy, G; Fitch, J P; McCutchen-Maloney, S

    2004-05-11

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

  13. Strategic Framework for the Defense Acquisition System Understanding Defense Consolidation

    National Research Council Canada - National Science Library

    Potts, Anthony W

    2007-01-01

    ...% of defense product sales annually. Defense consolidation has diminished the flexibility required for surge capacity, diminished competitive innovations in products, and reduced competitive pricing based on multiple sources for products...

  14. SDI (Strategic Defense Initiative) and the US defense posture

    Energy Technology Data Exchange (ETDEWEB)

    May, M.M.

    1986-07-01

    Issues surrounding the Strategic Defense Initiative are discussed. Comments are made on the research and development program and the effect of this program on the defensive posture of the United States.

  15. Strategic Framework for the Defense Acquisition System Understanding Defense Consolidation

    National Research Council Canada - National Science Library

    Potts, Anthony W

    2007-01-01

    The 1993 policy to promote the consolidation of the United States defense industry began a series of acquisitions and mergers that went beyond the intent of the policy and left the Department of Defense (DoD...

  16. Research on moving target defense based on SDN

    Science.gov (United States)

    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.

  17. Defense Technology Area Plan.

    Science.gov (United States)

    1996-05-01

    evacuation , missile defense, reconnaissance and surveillance, sea lane control, search and rescue, special operations, strategic and theater airlift...decontamination technology advances. Recently, novel types of polymeric support termed “ starburst ” dendrimer polymers have been developed. The ability to...threats • Optimize military performance; survival and stabilization of combat casualties • Provide the world’s best casualty evacuation and medical

  18. Auxins in defense strategies

    Czech Academy of Sciences Publication Activity Database

    Čarná, Mária; Repka, V.; Skůpa, Petr; Šturdík, E.

    2014-01-01

    Roč. 69, č. 10 (2014), s. 1255-1263 ISSN 0006-3088 R&D Projects: GA TA ČR TA01011802 Institutional support: RVO:61389030 Keywords : auxin * defense responses * JA Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection Impact factor: 0.827, year: 2014

  19. Hanford defense waste studies

    International Nuclear Information System (INIS)

    Napier, B.A.; Zimmerman, M.G.; Soldat, J.K.

    1981-01-01

    PNL is assisting Rockwell Hanford Operations to prepare a programmatic environmental impact statement for the management of Hanford defense nuclear waste. The Ecological Sciences Department is leading the task of calculation of public radiation doses from a large matrix of potential routine and accidental releases of radionuclides to the environment

  20. Ministries of Defense: Driving Force in Defense Restructuring

    OpenAIRE

    2003-01-01

    Introduction. For more effective democratic civilian control (and better defense decisions), Ministries of Defense bridge the gap between political institutions and the armed forces. These institutions translate political objectives into military capabilities. MODs, staffed with enough civilian defense experts, provide the continuity and stability needed in a democratic system.

  1. Sexual Responsivity and Ego Defenses

    Science.gov (United States)

    Schill, Thomas; Bekker, Demoyne

    1976-01-01

    The present study sought to determine whether high- and low-sexual responders on a double-entendre word association test differed in defensive preference on Gleser and Ihilevich's Defense Mechanism Inventory. (Author)

  2. Defense Logistics Agency Revenue Eliminations

    National Research Council Canada - National Science Library

    1996-01-01

    The issue of revenue eliminations was identified during our work on the Defense Logistics Agency portion of the Audit of Revenue Accounts in the FY 1996 Financial Statements of the Defense Business Operations Fund...

  3. Joint stabilizing projects in defense

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.; Browne, J.C.; Joseph, R.J.

    1992-06-01

    Joint defensive projects could increase stability and decrease the alert rates of strategic forces. Areas include the defense of the US, Commonwealth of Independent States (CIS), and their allies against third world threats; protection against each other`s accidental or unauthorized launches; and defense against intentional attacks. The most promising area appears to be defining interfaces for the handover of satellite warning and trajectory information, which applies to most phases of theater defense and mutual protection. 19 refs.

  4. Joint stabilizing projects in defense

    Energy Technology Data Exchange (ETDEWEB)

    Canavan, G.H.; Browne, J.C.; Joseph, R.J.

    1992-06-01

    Joint defensive projects could increase stability and decrease the alert rates of strategic forces. Areas include the defense of the US, Commonwealth of Independent States (CIS), and their allies against third world threats; protection against each other's accidental or unauthorized launches; and defense against intentional attacks. The most promising area appears to be defining interfaces for the handover of satellite warning and trajectory information, which applies to most phases of theater defense and mutual protection. 19 refs.

  5. Modulation of host immune responses by clinically relevant human DNA and RNA viruses.

    Science.gov (United States)

    Brander, C; Walker, B D

    2000-08-01

    Numerous mechanisms allow viruses to evade host immune surveillance, and new evasion strategies continue to be identified. In addition to interference with antigen processing and presentation, direct viral modulation of host immune responses can also be achieved by altering the host cytokine milieu and the development of immunoregulatory cells. A better understanding of these viral evasion strategies will help to define critical host defense mechanisms and will lead to novel immune-based therapeutic strategies in the future.

  6. Anti-sense expression of putrescine N-methyltransferase confirms defensive role of nicotine in Nicotiana sylvestris against Manduca sexta

    NARCIS (Netherlands)

    Voelckel, C.; Krugel, T.; Gase, K.; Heidrich, N.; Van Dam, N.M.; Winz, R.; Baldwin, I.T.

    2001-01-01

    Several lines of evidence support the defensive function of nicotine production in the Nicotiana genus against a range of herbivores, but the evidence is largely correlative. To suppress nicotine production in planta and to test its defensive function, we expressed DNA of putrescine N-methyl

  7. Belowground herbivory and plant defenses

    NARCIS (Netherlands)

    Van Dam, N.M.

    2009-01-01

    Belowground-feeding herbivores may be very destructive to plants. Roots are known to produce various defense compounds to protect themselves against these herbivores, both with direct and indirect—inducible—defense compounds. Recent literature reviews reveal no overall pattern for root-shoot defense

  8. Cross talk in defense signaling

    NARCIS (Netherlands)

    Koornneef, A.; Pieterse, C.M.J.

    2008-01-01

    Plants are equipped with an array of defense mechanisms to protect themselves against attack by herbivorous insects and microbial pathogens. Some of these defense mechanisms are preexisting, whereas others are only activated upon insect or pathogen invasion. Induced defense responses entail fitness

  9. Defense Mechanisms in Group Counseling.

    Science.gov (United States)

    Clark, Arthur J.

    1992-01-01

    Presents considerations and strategies for conceptualizing, recognizing, and modifying defense mechanisms through the group counseling process. Provides awareness of defense mechanisms in planning for and implementation of group counseling, describes interaction patterns for identifying defenses among group participants, and clarifies modification…

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

    Science.gov (United States)

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

    2012-01-01

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

  11. Avoid, attack or do both? Behavioral and physiological adaptations in natural enemies faced with novel hosts

    Directory of Open Access Journals (Sweden)

    Brown Sam P

    2005-11-01

    Full Text Available Abstract Background Confronted with well-defended, novel hosts, should an enemy invest in avoidance of these hosts (behavioral adaptation, neutralization of the defensive innovation (physiological adaptation or both? Although simultaneous investment in both adaptations may first appear to be redundant, several empirical studies have suggested a reinforcement of physiological resistance to host defenses with additional avoidance behaviors. To explain this paradox, we develop a mathematical model describing the joint evolution of behavioral and physiological adaptations on the part of natural enemies to their host defenses. Our specific goals are (i to derive the conditions that may favor the simultaneous investment in avoidance and physiological resistance and (ii to study the factors that govern the relative investment in each adaptation mode. Results Our results show that (i a simultaneous investment may be optimal if the fitness costs of the adaptive traits are accelerating and the probability of encountering defended hosts is low. When (i holds, we find that (ii the more that defended hosts are rare and/or spatially aggregated, the more behavioral adaptation is favored. Conclusion Despite their interference, physiological resistance to host defensive innovations and avoidance of these same defenses are two strategies in which it may be optimal for an enemy to invest in simultaneously. The relative allocation to each strategy greatly depends on host spatial structure. We discuss the implications of our findings for the management of invasive plant species and the management of pest resistance to new crop protectants or varieties.

  12. Climate Change and Defense against Pathogens in Plants.

    Science.gov (United States)

    Newton, Adrian C; Torrance, Lesley; Holden, Nicola; Toth, Ian K; Cooke, David E L; Blok, Vivian; Gilroy, Eleanor M

    2012-01-01

    Most reviews of climate change are epidemiological, focusing on impact assessment and risk mapping. However, there are many reports of the effects of environmental stress factors on defense mechanisms in plants against pathogens. We review those representative of key climate change-related stresses to determine whether there are any patterns or trends in adaptation responses. We recognize the complexity of climate change itself and the multitrophic nature of the complex biological interactions of plants, microbes, soil, and the environment and, therefore, the difficulty of reductionist dissection approaches to resolving the problems. We review host defense genes, germplasm, and environmental interactions in different types of organisms but find no significant group-specific trends. Similarly, we review by host defense mechanism type and by host-pathogen trophic relationship but identify no dominating mechanism for stress response. However, we do identify core stress response mechanisms playing key roles in multiple response pathways whether to biotic or abiotic stress. We suggest that these should be central to mechanistic climate change plant defense research. We also recognize biodiversity, heterogeneity, and the need for understanding stress in a true systems biology approach as being essential components of progressing our understanding of and response to climate change. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Defense on the Move: Ant-Based Cyber Defense

    Energy Technology Data Exchange (ETDEWEB)

    Fink, Glenn A.; Haack, Jereme N.; McKinnon, Archibald D.; Fulp, Errin W.

    2014-04-15

    Many common cyber defenses (like firewalls and IDS) are as static as trench warfare allowing the attacker freedom to probe them at will. The concept of Moving Target Defense (MTD) adds dynamism to the defender side, but puts the systems to be defended themselves in motion, potentially at great cost to the defender. An alternative approach is a mobile resilient defense that removes attackers’ ability to rely on prior experience without requiring motion in the protected infrastructure itself. The defensive technology absorbs most of the cost of motion, is resilient to attack, and is unpredictable to attackers. The Ant-Based Cyber Defense (ABCD) is a mobile resilient defense providing a set of roaming, bio-inspired, digital-ant agents working with stationary agents in a hierarchy headed by a human supervisor. The ABCD approach provides a resilient, extensible, and flexible defense that can scale to large, multi-enterprise infrastructures like the smart electric grid.

  14. Manganese acquisition and homeostasis at the host-pathogen interface

    OpenAIRE

    Lisher, John P.; Giedroc, David P.

    2013-01-01

    Pathogenic bacteria acquire transition metals for cell viability and persistence of infection in competition with host nutritional defenses. The human host employs a variety of mechanisms to stress the invading pathogen with both cytotoxic metal ions and oxidative and nitrosative insults while withholding essential transition metals from the bacterium. For example, the S100 family protein calprotectin (CP) found in neutrophils is a calcium-activated chelator of extracellular Mn and Zn and i...

  15. The effects of host-feeding on stability of discrete-time host-parasitoid population dynamic models.

    Science.gov (United States)

    Emerick, Brooks; Singh, Abhyudai

    2016-02-01

    Discrete-time models are the traditional approach for capturing population dynamics of a host-parasitoid system. Recent work has introduced a semi-discrete framework for obtaining model update functions that connect host-parasitoid population levels from year-to-year. In particular, this framework uses differential equations to describe the host-parasitoid interaction during the time of year when they come in contact, allowing specific behaviors to be mechanistically incorporated. We use the semi-discrete approach to study the effects of host-feeding, which occurs when a parasitoid consumes a potential host larva without ovipositing. We find that host-feeding by itself cannot stabilize the system, and both populations exhibit behavior similar to the Nicholson-Bailey model. However, when combined with stabilizing mechanisms such as density-dependent host mortality, host-feeding contracts the region of parameter space that allows for a stable host-parasitoid equilibrium. In contrast, when combined with a density-dependent parasitoid attack rate, host-feeding expands the non-zero equilibrium stability region. Our results show that host-feeding causes inefficiency in the parasitoid population, which yields a higher population of hosts per generation. This suggests that host-feeding may have limited long-term impact in terms of suppressing host levels for biological control applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Pressure suppression device

    International Nuclear Information System (INIS)

    Ichiki, Tadaharu; Funahashi, Toshihiro.

    1976-01-01

    Purpose: To provide a structure which permits the absorption of shocks and vibratory load produced on the floor of a pressure suppression chamber due to nitrogen gas or the like discharged into pool water in the pressure suppression chamber at the time of a loss-of-coolant accident. Constitution: A pressure suppression chamber accommodating pool water is comprised of a bottom wall and side walls constructed of concrete on the inner side of a liner. By providing concrete on the bottom surface and side wall surfaces of a pressure suppression chamber, it is possible to prevent non-condensing gas and steam exhausted from the vent duct and exhaust duct of a main vapor escapement safety valve exhaust duct from exerting impact forces and vibratory forces upon the bottom and side surfaces of the pressure suppression chamber. (Horiuchi, T.)

  17. Boomeranging in structural defense

    Science.gov (United States)

    Marler, Thomas E.

    2012-01-01

    Plant defensive behaviors that resist arthropod herbivory include trichome-mediated defenses, and variation in plant trichome morphology and abundance provides examples of the mechanistic complexities of insect-plant interactions. Trichomes were removed from Cycas revoluta cataphylls on the island of Guam to reveal Aulacaspis yasumatsui scale infestation, and predation of the newly exposed insects by pre-existing Rhyzobius lophanthae beetles commenced within one day. The quotient of predated/total scale insects was 0.5 by day 4 and stabilized at that found on adjacent glabrous leaves in about one week. The trichome phenotype covering the C. revoluta cataphyll complex offers the invasive A. yasumatsui armored scale effectual enemy-free space in this system. This pest and predator share no known evolutionary history with C. revoluta, therefore, the adaptive significance of this plant behavior in natural habitat is not yet known. PMID:22990448

  18. Defense mechanisms reported by patients with borderline personality disorder and axis II comparison subjects over 16 years of prospective follow-up: description and prediction of recovery.

    Science.gov (United States)

    Zanarini, Mary C; Frankenburg, Frances R; Fitzmaurice, Garrett

    2013-01-01

    The authors assessed the defensive functioning of 290 patients with borderline personality disorder and compared it with that of 72 patients with other forms of axis II psychopathology over 16 years of prospective follow-up. They also assessed the relationship between time-varying defenses and recovery from borderline personality disorder. The Defense Style Questionnaire, a self-report measure with demonstrated criterion validity and internal consistency, was initially administered at study entry. It was readministered at eight contiguous 2-year follow-up periods. Borderline patients had significantly lower scores than axis II comparison subjects on one mature defense mechanism (suppression) and significantly higher scores on seven of the other 18 defenses studied: one neurotic-level defense (undoing), four immature defenses (acting out, emotional hypochondriasis, passive aggression, and projection), and two image-distorting/borderline defenses (projective identification and splitting). Over the follow-up period, borderline patients showed significant improvement on 13 of the 19 defenses studied, with significantly higher scores over time on one mature defense (anticipation) and significantly lower scores on two neurotic defenses (isolation and undoing), all immature defenses, and all image-distorting/borderline defenses except primitive idealization. In addition, four time-varying defense mechanisms were found to predict time to recovery: humor, acting out, emotional hypochondriasis, and projection. Taken together, these results suggest that the longitudinal defensive functioning of borderline patients is distinct and improves substantially over time. They also suggest that immature defenses are the best predictor of time to recovery.

  19. Adenovirus core protein VII down-regulates the DNA damage response on the host genome.

    Science.gov (United States)

    Avgousti, Daphne C; Della Fera, Ashley N; Otter, Clayton J; Herrmann, Christin; Pancholi, Neha J; Weitzman, Matthew D

    2017-08-09

    Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier for successful infection. The adenovirus genome is packaged with protein VII, a viral-encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome. Here, we show that protein VII at cellular chromatin results in a significant decrease in accumulation of phosphorylated H2AX (γH2AX) following irradiation, indicating that protein VII inhibits DDR signaling. The oncoprotein SET was recently suggested to modulate the DDR by affecting access of repair proteins to chromatin. Since protein VII binds SET, we investigated a role for SET in DDR inhibition by protein VII. We show that knockdown of SET partially rescues the protein VII-induced decrease in γH2AX accumulation on the host genome, suggesting that SET is required for inhibition. Finally, we show that knockdown of SET also allows ATM to localize to incoming viral genomes bound by protein VII during infection with a mutant lacking early region E4. Together, our data suggest that the protein VII-SET interaction contributes to DDR evasion by adenovirus. Our results provide an additional example of a strategy used by adenovirus to manipulate the host DDR and show how viruses can modify cellular processes through manipulation of host chromatin. IMPORTANCE The DNA damage response (DDR) is a cellular network crucial for maintaining genome integrity. DNA viruses replicating in the nucleus challenge the resident genome and must overcome cellular responses, including the DDR. Adenoviruses are prevalent human pathogens that can cause a

  20. Defense against Space Weapons,

    Science.gov (United States)

    1983-02-24

    which can be used at present are space defense missiles, killer satellites, high energy laser weapons and particle beam weapons. In 1962, the U.S... laser weapons and particle beam weapons have the ad- 4vantages of high power, concentrated energy, hit accuracy, and conven- ience of use. They have... weapons development amounts to 5 US$200,000,000. At present, irradiation by a laser weapon operating on the earth’s surface can cause optical and infrared

  1. Defense Primer: Procurement

    Science.gov (United States)

    2017-02-10

    capital assets, such as an F-35 Joint Strike Fighter or a Virginia-class submarine. Investment costs are distinguished from expenses, which are...procurement funds before a formal Milestone C approval. How else does DOD purchase goods and services? How does DOD procurement relate to defense...purchase services (e.g., research, architectural design, or cleaning services) and smaller goods (e.g., gauze or light bulbs) because such purchases

  2. Host Ecology Rather Than Host Phylogeny Drives Amphibian Skin Microbial Community Structure in the Biodiversity Hotspot of Madagascar

    OpenAIRE

    Bletz, Molly C.; Archer, Holly; Harris, Reid N.; McKenzie, Valerie J.; Rabemananjara, Falitiana C. E.; Rakotoarison, Andolalao; Vences, Miguel

    2017-01-01

    Host-associated microbiotas of vertebrates are diverse and complex communities that contribute to host health. In particular, for amphibians, cutaneous microbial communities likely play a significant role in pathogen defense; however, our ecological understanding of these communities is still in its infancy. Here, we take advantage of the fully endemic and locally species-rich amphibian fauna of Madagascar to investigate the factors structuring amphibian skin microbiota on a large scale. Usin...

  3. Interaction of entomopathogenic fungi with the host immune system.

    Science.gov (United States)

    Qu, Shuang; Wang, Sibao

    2018-02-02

    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.

  4. Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium.

    Science.gov (United States)

    Pukkila-Worley, Read; Ausubel, Frederick M

    2012-02-01

    Intestinal epithelial cells provide an essential line of defense for Caernohabditis elegans against ingested pathogens. Because nematodes consume microorganisms as their food source, there has presumably been selection pressure to evolve and maintain immune defense mechanisms within the intestinal epithelium. Here we review recent advances that further define the immune signaling network within these cells and suggest mechanisms used by the nematode to monitor for infection. In reviewing studies of pathogenesis that use this simple model system, we hope to illustrate some of the basic principles of epithelial immunity that may also be of relevance in higher order hosts. Copyright © 2012. Published by Elsevier Ltd.

  5. Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

    Science.gov (United States)

    Kuss, Sharon K.; Mata, Miguel A.; Zhang, Liang; Fontoura, Beatriz M. A.

    2013-01-01

    Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses. PMID:23872491

  6. Failure of respiratory defenses in the pathogenesis of bacterial pneumonia of cattle.

    Science.gov (United States)

    Caswell, J L

    2014-03-01

    The respiratory system is well defended against inhaled bacteria by a dynamic system of interacting layers, including mucociliary clearance, host defense factors including antimicrobial peptides in the epithelial lining fluid, proinflammatory responses of the respiratory epithelium, resident alveolar macrophages, and recruited neutrophils and monocytes. Nevertheless, these manifold defenses are susceptible to failure as a result of stress, glucocorticoids, viral infections, abrupt exposure to cold air, and poor air quality. When some of these defenses fail, the lung can be colonized by bacterial pathogens that are equipped to evade the remaining defenses, resulting in the development of pneumonia. This review considers the mechanisms by which these predisposing factors compromise the defenses of the lung, with a focus on the development of bacterial pneumonia in cattle and supplemented with advances based on mouse models and the study of human disease. Deepening our understanding of how the respiratory defenses fail is expected to lead to interventions that restore these dynamic immune responses and prevent disease.

  7. DEFENSE PROGRAMS RISK MANAGEMENT FRAMEWORK

    Directory of Open Access Journals (Sweden)

    Constantin PREDA

    2012-01-01

    Full Text Available For the past years defense programs have faced delays in delivering defense capabilities and budget overruns. Stakeholders are looking for ways to improve program management and the decision making process given the very fluid and uncertain economic and political environment. Consequently, they have increasingly resorted to risk management as the main management tool for achieving defense programs objectives and for delivering the defense capabilities strongly needed for the soldiers on the ground on time and within limited defense budgets. Following a risk management based decision-making approach the stakeholders are expected not only to protect program objectives against a wide range of risks but, at the same time, to take advantage of the opportunities to increase the likelihood of program success. The prerequisite for making risk management the main tool for achieving defense programs objectives is the design and implementation of a strong risk management framework as a foundation providing an efficient and effective application of the best risk management practices. The aim of this paper is to examine the risk management framework for defense programs based on the ISO 31000:2009 standard, best risk management practices and the defense programs’ needs and particularities. For the purposes of this article, the term of defense programs refers to joint defense programs.

  8. Defense Primer: The National Defense Budget Function (050)

    Science.gov (United States)

    2017-03-17

    provides a framework for examining spending patterns of the federal government by category of activity, rather than by agency or type of financing ...federal spending. Since federal agencies often have diverse, overlapping responsibilities , it is not uncommon for them to be associated with multiple...agency responsible for approximately 96% of spending within the National Defense Budget (050). Defense Primer: The National Defense Budget Function

  9. Menstrual suppression for adolescents.

    Science.gov (United States)

    Altshuler, Anna Lea; Hillard, Paula J Adams

    2014-10-01

    The purpose of this review is to highlight the recent literature and emerging data describing clinical situations in which menstrual suppression may improve symptoms and quality of life for adolescents. A variety of conditions occurring frequently in adolescents and young adults, including heavy menstrual bleeding, and dysmenorrhea as well as gynecologic conditions such as endometriosis and pelvic pain, can safely be improved or alleviated with appropriate menstrual management. Recent publications have highlighted the efficacy and benefit of extended cycle or continuous combined oral contraceptives, the levonorgestrel intrauterine device, and progestin therapies for a variety of medical conditions. This review places menstrual suppression in an historical context, summarizes methods of hormonal therapy that can suppress menses, and reviews clinical conditions for which menstrual suppression may be helpful.

  10. Cryogenic Acoustic Suppression Testing

    Data.gov (United States)

    National Aeronautics and Space Administration — A proof-of-concept method utilizing a cryogenic fluid for acoustic suppression in rocket engine testing environments will be demonstrated. It is hypothesized that...

  11. Synthetic Plant Defense Elicitors

    Directory of Open Access Journals (Sweden)

    Yasemin eBektas

    2015-01-01

    Full Text Available To defend themselves against invading pathogens plants utilize a complex regulatory network that coordinates extensive transcriptional and metabolic reprogramming. Although many of the key players of this immunity-associated network are known, the details of its topology and dynamics are still poorly understood. As an alternative to forward and reverse genetic studies, chemical genetics-related approaches based on bioactive small molecules have gained substantial popularity in the analysis of biological pathways and networks. Use of such molecular probes can allow researchers to access biological space that was previously inaccessible to genetic analyses due to gene redundancy or lethality of mutations. Synthetic elicitors are small drug like molecules that induce plant defense responses, but are distinct from known natural elicitors of plant immunity. While the discovery of the some synthetic elicitors had already been reported in the 1970s, recent breakthroughs in combinatorial chemical synthesis now allow for inexpensive high-throughput screens for bioactive plant defense-inducing compounds. Along with powerful reverse genetics tools and resources available for model plants and crop systems, comprehensive collections of new synthetic elicitors will likely allow plant scientists to study the intricacies of plant defense signaling pathways and networks in an unparalleled fashion. As synthetic elicitors can protect crops from diseases, without the need to be directly toxic for pathogenic organisms, they may also serve as promising alternatives to conventional biocidal pesticides, which often are harmful for the environment, farmers and consumers. Here we are discussing various types of synthetic elicitors that have been used for studies on the plant immune system, their modes-of-action as well as their application in crop protection.

  12. Functionally redundant RXLR effectors from Phytophthora infestans act at different steps to suppress early flg22-triggered immunity.

    Directory of Open Access Journals (Sweden)

    Xiangzi Zheng

    2014-04-01

    Full Text Available Genome sequences of several economically important phytopathogenic oomycetes have revealed the presence of large families of so-called RXLR effectors. Functional screens have identified RXLR effector repertoires that either compromise or induce plant defense responses. However, limited information is available about the molecular mechanisms underlying the modes of action of these effectors in planta. The perception of highly conserved pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs, such as flg22, triggers converging signaling pathways recruiting MAP kinase cascades and inducing transcriptional re-programming, yielding a generic anti-microbial response. We used a highly synchronizable, pathogen-free protoplast-based assay to identify a set of RXLR effectors from Phytophthora infestans (PiRXLRs, the causal agent of potato and tomato light blight that manipulate early stages of flg22-triggered signaling. Of thirty-three tested PiRXLR effector candidates, eight, called Suppressor of early Flg22-induced Immune response (SFI, significantly suppressed flg22-dependent activation of a reporter gene under control of a typical MAMP-inducible promoter (pFRK1-Luc in tomato protoplasts. We extended our analysis to Arabidopsis thaliana, a non-host plant species of P. infestans. From the aforementioned eight SFI effectors, three appeared to share similar functions in both Arabidopsis and tomato by suppressing transcriptional activation of flg22-induced marker genes downstream of post-translational MAP kinase activation. A further three effectors interfere with MAMP signaling at, or upstream of, the MAP kinase cascade in tomato, but not in Arabidopsis. Transient expression of the SFI effectors in Nicotiana benthamiana enhances susceptibility to P. infestans and, for the most potent effector, SFI1, nuclear localization is required for both suppression of MAMP signaling and virulence function. The present study provides a framework to decipher the

  13. Sodium fire suppression

    International Nuclear Information System (INIS)

    Malet, J.C.

    1979-01-01

    Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

  14. Phenomenon of Psychological Defense

    Directory of Open Access Journals (Sweden)

    Elena T. Sokolova

    2011-01-01

    Full Text Available The author discusses the controversial issues of formation and functioning of psy¬chological defense mechanisms in ontogenesis and in personality disorders as they are represented in classical and contemporary psychoanalysis, in cognitivism and communication theory. The paper emphasizes the role of cognitive organi¬zation (style, sign-symbolic mediation, representative system of object relations and attachments in individual typological variability of the level organization of ciency of personal and social adaptation, in maturity and mental health of personality

  15. Nanomaterials for Defense Applications

    Science.gov (United States)

    Turaga, Uday; Singh, Vinitkumar; Lalagiri, Muralidhar; Kiekens, Paul; Ramkumar, Seshadri S.

    Nanotechnology has found a number of applications in electronics and healthcare. Within the textile field, applications of nanotechnology have been limited to filters, protective liners for chemical and biological clothing and nanocoatings. This chapter presents an overview of the applications of nanomaterials such as nanofibers and nanoparticles that are of use to military and industrial sectors. An effort has been made to categorize nanofibers based on the method of production. This chapter particularly focuses on a few latest developments that have taken place with regard to the application of nanomaterials such as metal oxides in the defense arena.

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

    Science.gov (United States)

    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].

  17. Antipredator defenses predict diversification rates

    OpenAIRE

    Arbuckle, Kevin; Speed, Michael P.

    2015-01-01

    Prey use a variety of mechanisms to avoid the risk of predation, including chemical defense, camouflage, and conspicuous coloration. Here we show that variation in these forms of protection can have profound effects on macroevolutionary patterns in amphibians. Chemical defense and conspicuous coloration both increase speciation rates, in line with the “escape-and-radiate” hypothesis. However, chemical defense also increases extinction rates, lowering net diversification. We therefore show tha...

  18. Compatibility in the Ustilago maydis-maize interaction requires inhibition of host cysteine proteases by the fungal effector Pit2.

    Directory of Open Access Journals (Sweden)

    André N Mueller

    2013-02-01

    Full Text Available The basidiomycete Ustilago maydis causes smut disease in maize, with large plant tumors being formed as the most prominent disease symptoms. During all steps of infection, U. maydis depends on a biotrophic interaction, which requires an efficient suppression of plant immunity. In a previous study, we identified the secreted effector protein Pit2, which is essential for maintenance of biotrophy and induction of tumors. Deletion mutants for pit2 successfully penetrate host cells but elicit various defense responses, which stops further fungal proliferation. We now show that Pit2 functions as an inhibitor of a set of apoplastic maize cysteine proteases, whose activity is directly linked with salicylic-acid-associated plant defenses. Consequently, protease inhibition by Pit2 is required for U. maydis virulence. Sequence comparisons with Pit2 orthologs from related smut fungi identified a conserved sequence motif. Mutation of this sequence caused loss of Pit2 function. Consequently, expression of the mutated protein in U. maydis could not restore virulence of the pit2 deletion mutant, indicating that the protease inhibition by Pit2 is essential for fungal virulence. Moreover, synthetic peptides of the conserved sequence motif showed full activity as protease inhibitor, which identifies this domain as a new, minimal protease inhibitor domain in plant-pathogenic fungi.

  19. Mycobacterium tuberculosis Transcription Machinery: Ready To Respond to Host Attacks

    Science.gov (United States)

    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

  20. Staphylococcus aureus strategies to evade the host acquired immune response.

    Science.gov (United States)

    Goldmann, Oliver; Medina, Eva

    2017-09-15

    Staphylococcus aureus poses a significant public-health problem. Infection caused by S. aureus can manifest as acute or long-lasting persistent diseases that are often refractory to antibiotic and are associated with significant morbidity and mortality. To develop more effective strategies for preventing or treating these infections, it is crucial to understand why the immune response is incapable to eradicate the bacterium. When S. aureus first infect the host, there is a robust activation of the host innate immune responses. Generally, S. aureus can survive this initial interaction due to the expression of a wide array of virulence factors that interfere with the host innate immune defenses. After this initial interaction the acquired immune response is the arm of the host defenses that will try to clear the pathogen. However, S. aureus is capable of maintaining infection in the host even in the presence of a robust antigen-specific immune response. Thus, understanding the mechanisms underlying the ability of S. aureus to escape immune surveillance by the acquired immune response will help uncover potentially important targets for the development of immune-based adjunctive therapies and more efficient vaccines. There are several lines of evidence that lead us to believe that S. aureus can directly or indirectly disable the acquired immune response. This review will discuss the different immune evasion strategies used by S. aureus to modulate the different components of the acquired immune defenses. Copyright © 2017 Elsevier GmbH. All rights reserved.

  1. Disease Suppressive Soils: New Insights from the Soil Microbiome.

    Science.gov (United States)

    Schlatter, Daniel; Kinkel, Linda; Thomashow, Linda; Weller, David; Paulitz, Timothy

    2017-11-01

    Soils suppressive to soilborne pathogens have been identified worldwide for almost 60 years and attributed mainly to suppressive or antagonistic microorganisms. Rather than identifying, testing and applying potential biocontrol agents in an inundative fashion, research into suppressive soils has attempted to understand how indigenous microbiomes can reduce disease, even in the presence of the pathogen, susceptible host, and favorable environment. Recent advances in next-generation sequencing of microbiomes have provided new tools to reexamine and further characterize the nature of these soils. Two general types of suppression have been described: specific and general suppression, and theories have been developed around these two models. In this review, we will present three examples of currently-studied model systems with features representative of specific and general suppressiveness: suppression to take-all (Gaeumannomyces graminis var. tritici), Rhizoctonia bare patch of wheat (Rhizoctonia solani AG-8), and Streptomyces. To compare and contrast the two models of general versus specific suppression, we propose a number of hypotheses about the nature and ecology of microbial populations and communities of suppressive soils. We outline the potential and limitations of new molecular techniques that can provide novel ways of testing these hypotheses. Finally, we consider how this greater understanding of the phytobiome can facilitate sustainable disease management in agriculture by harnessing the potential of indigenous soil microbes.

  2. An image classification approach to analyze the suppression of plant immunity by the human pathogen Salmonella Typhimurium

    Directory of Open Access Journals (Sweden)

    Schikora Marek

    2012-07-01

    Full Text Available Abstract Background The enteric pathogen Salmonella is the causative agent of the majority of food-borne bacterial poisonings. Resent research revealed that colonization of plants by Salmonella is an active infection process. Salmonella changes the metabolism and adjust the plant host by suppressing the defense mechanisms. In this report we developed an automatic algorithm to quantify the symptoms caused by Salmonella infection on Arabidopsis. Results The algorithm is designed to attribute image pixels into one of the two classes: healthy and unhealthy. The task is solved in three steps. First, we perform segmentation to divide the image into foreground and background. In the second step, a support vector machine (SVM is applied to predict the class of each pixel belonging to the foreground. And finally, we do refinement by a neighborhood-check in order to omit all falsely classified pixels from the second step. The developed algorithm was tested on infection with the non-pathogenic E. coli and the plant pathogen Pseudomonas syringae and used to study the interaction between plants and Salmonella wild type and T3SS mutants. We proved that T3SS mutants of Salmonella are unable to suppress the plant defenses. Results obtained through the automatic analyses were further verified on biochemical and transcriptome levels. Conclusion This report presents an automatic pixel-based classification method for detecting “unhealthy” regions in leaf images. The proposed method was compared to existing method and showed a higher accuracy. We used this algorithm to study the impact of the human pathogenic bacterium Salmonella Typhimurium on plants immune system. The comparison between wild type bacteria and T3SS mutants showed similarity in the infection process in animals and in plants. Plant epidemiology is only one possible application of the proposed algorithm, it can be easily extended to other detection tasks, which also rely on color information, or

  3. An image classification approach to analyze the suppression of plant immunity by the human pathogen Salmonella Typhimurium.

    Science.gov (United States)

    Schikora, Marek; Neupane, Balram; Madhogaria, Satish; Koch, Wolfgang; Cremers, Daniel; Hirt, Heribert; Kogel, Karl-Heinz; Schikora, Adam

    2012-07-19

    The enteric pathogen Salmonella is the causative agent of the majority of food-borne bacterial poisonings. Resent research revealed that colonization of plants by Salmonella is an active infection process. Salmonella changes the metabolism and adjust the plant host by suppressing the defense mechanisms. In this report we developed an automatic algorithm to quantify the symptoms caused by Salmonella infection on Arabidopsis. The algorithm is designed to attribute image pixels into one of the two classes: healthy and unhealthy. The task is solved in three steps. First, we perform segmentation to divide the image into foreground and background. In the second step, a support vector machine (SVM) is applied to predict the class of each pixel belonging to the foreground. And finally, we do refinement by a neighborhood-check in order to omit all falsely classified pixels from the second step. The developed algorithm was tested on infection with the non-pathogenic E. coli and the plant pathogen Pseudomonas syringae and used to study the interaction between plants and Salmonella wild type and T3SS mutants. We proved that T3SS mutants of Salmonella are unable to suppress the plant defenses. Results obtained through the automatic analyses were further verified on biochemical and transcriptome levels. This report presents an automatic pixel-based classification method for detecting "unhealthy" regions in leaf images. The proposed method was compared to existing method and showed a higher accuracy. We used this algorithm to study the impact of the human pathogenic bacterium Salmonella Typhimurium on plants immune system. The comparison between wild type bacteria and T3SS mutants showed similarity in the infection process in animals and in plants. Plant epidemiology is only one possible application of the proposed algorithm, it can be easily extended to other detection tasks, which also rely on color information, or even extended to other features.

  4. Characterization of the Wheat Stripe Rust (Puccinia striiformis f. sp. tritici) Fungal Effector Candidate PEC6 and Its Corresponding Host Targets

    DEFF Research Database (Denmark)

    Liu, Changhai

    Stripe rust cause