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Host Defence (host + defence)
Terms modified by Host Defence Selected AbstractsInnate immunity and biodefence vaccinesCELLULAR MICROBIOLOGY, Issue 11 2003Nicholas M. Valiante Summary Host defence in vertebrates is achieved by the integration of two distinct arms of the immune system: the innate and adaptive responses. The innate response acts early after infection (within minutes), detecting and responding to broad cues from invading pathogens. The adaptive response takes time (days to weeks) to become effective, but provides the fine antigenic specificity required for complete elimination of the pathogen and the generation of immunologic memory. Antigen-independent recognition of pathogens by the innate immune system leads to the rapid mobilization of immune effector and regulatory mechanisms that provide the host with three critical advantages: (i) initiating the immune response (both innate and adaptive) and providing the inflammatory and co-stimulatory context for antigen recognition; (ii) mounting a first line of defence, thereby holding the pathogen in check during the maturation of the adaptive response; and (iii) steering the adaptive immune system towards the cellular or humoral responses most effective against the particular infectious agent. The quest for safer and more effective vaccines and immune-based therapies has taken on a sudden urgency with the increased threat of bioterrorism. Only a handful of vaccines covering a small proportion of potential biowarfare agents are available for human use (e.g. anthrax and small pox) and these suffer from poor safety profiles. Therefore, next generation biodefence-related vaccines and therapies with improved safety and the capacity to induce more rapid, more potent and broader protection are needed. To this end, strategies to target both the innate and adaptive immune systems will be required. [source] A comparison of the host-searching efficiency of two larval parasitoids of Plutella xylostellaECOLOGICAL ENTOMOLOGY, Issue 1 2002Xin-Geng Wang Summary 1. A host specialist parasitoid is thought to have greater efficiency in locating hosts or greater ability to overcome host defence than a generalist species. This leads to the prediction that a specialist should locate and parasitise more hosts than a generalist in a given arena. The work reported here tested these predictions by comparing the host-searching behaviour of Diadegma semiclausum (a specialist) and Cotesia plutellae (an oligophagous species), two parasitoids of larval Plutella xylostella. 2. Both parasitoids employed antennal search and ovipositor search when seeking hosts but D. semiclausum also seemed to use visual perception in the immediate vicinity of hosts. 3. Larvae of P. xylostella avoided detection by parasitoids by moving away from damaged plant parts after short feeding bouts. When they encountered parasitoids, the larvae wriggled vigorously as they retreated and often hung from silk threads after dropping from a plant. 4. These two parasitoids differed in their responses to host defences. Diadegma semiclausum displayed a wide-area search around feeding damage and waited near the silk thread for a suspended host to climb up to the leaf, then attacked it again. Cotesia plutellae displayed an area-restricted search and usually pursued the host down the silk thread onto the ground. 5. Diadegma semiclausum showed a relatively fixed behavioural pattern leading to oviposition but C. plutellae exhibited a more plastic behavioural pattern. 6. The time spent by the two parasitoids on different plants increased with increasing host density, but the time spent either on all plants or a single plant by D. semiclausum was longer than that of C. plutellae. Diadegma semiclausum visited individual plants more frequently than C. plutellae before it left the patch, and stung hosts at more than twice the rate of C. plutellae. 7. The results indicated that the host-location strategies employed by D. semiclausum were adapted better to the host's defensive behaviour, and thus it was more effective at detecting and parasitising the host than was C. plutellae. [source] Temperature checks the Red Queen?ECOLOGY LETTERS, Issue 1 2003Resistance, virulence in a fluctuating environment Abstract Numerous studies have revealed genetic variation in resistance and susceptibility in host,parasite interactions and therefore the potential for frequency-dependent selection (Red Queen dynamics). Few studies, if any, have considered the abiotic environment as a mediating factor in these interactions. Using the pea aphid, Acyrthosiphon pisum, and its fungal pathogen, Erynia neoaphidis, as a model host,parasite system, we demonstrate how temperature can mediate the expression of genotypic variation for susceptibility and virulence. Whilst previous studies have revealed among-clone variation in aphid resistance to this pathogen, we show that resistance rankings derived from assessments at one temperature, are not conserved across differing temperature regimes. We suggest that variation in environmental temperature, through its nonlinear impact on parasite virulence and host defence, may contribute to the general lack of evidence for frequency-dependent selection in field systems. [source] Nramp1 -functionality increases iNOS expression via repression of IL-10 formationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2008Gernot Fritsche Abstract In mice, resistance to certain intracellular microbes depends on the expression of a late phagosomal protein termed natural-resistance associated macrophage protein 1 (Nramp1, Slc11a1). Nramp1- functionality is associated with alterations of cellular iron homeostasis and a sustained pro-inflammatory immune response, including the formation of the antimicrobial effector molecule NO. To investigate the underlying mechanism we used RAW-264.7 murine macrophage cells stably transfected with a functional Nramp1 allele (RAW-37) or Nramp1 non-functional controls (RAW-21). We found that the production of and signalling by the anti-inflammatory cytokine IL-10 was significantly enhanced in macrophages lacking functional Nramp1. Upon infection of macrophages with Salmonella typhimurium pathogen survival was significantly better in RAW-21 than in RAW-37, which inversely correlated to NO and TNF-, formation. Addition of a neutralising anti-IL-10 antibody to RAW-21 cells led to a significantly reduced survival of S. typhimurium within these cells and enhanced formation of NO and TNF-, reaching levels comparable to that observed in cells bearing functional Nramp1. Oppositely, supplementation of iron to RAW-21 cells further increased IL-10 formation. Thus, Nramp1 mediates effective host defence in part via suppression of excessive IL-10 production which may relate to Nramp1- mediated reduction of cellular iron pools, thus strengthening antimicrobial effector mechanisms. [source] The acute-phase response impairs host defence against Enterococcus faecium peritonitisIMMUNOLOGY, Issue 1pt2 2009Masja Leendertse Summary Enterococcus faecium is an emerging pathogen that causes infections in hospitalized patients with various co-morbid diseases. These underlying diseases are often associated with an acute-phase response that renders patients vulnerable to nosocomial infections. To study the influence of the acute-phase response induced by sterile tissue injury on host defence against E. faecium, mice were injected subcutaneously with either turpentine or casein 1 day before intraperitoneal infection with E. faecium. Control mice were subcutaneously injected with saline or sodium bicarbonate, respectively. Turpentine and casein induced an acute-phase response as reflected by increases in the plasma concentrations of interleukin-6, serum amyloid P and C3. A pre-existent acute-phase response in mice was associated with a strongly reduced capacity to clear E. faecium, resulting in prolonged bacteraemia for several days. The inflammatory response to E. faecium was impaired in mice with an acute-phase response, as shown by reduced capacity to mount a neutrophilic leucocytosis in peripheral blood and by decreased local cytokine concentrations. These data indicate that the acute-phase response impairs host defence against E. faecium, suggesting that this condition may contribute to the increased vulnerability of critically ill patients to enterococcal infections. [source] Elevation of interleukin-18 in chronic hepatitis C: implications for hepatitis C virus pathogenesisIMMUNOLOGY, Issue 1pt2 2009Arpita Sharma Summary The outcome of hepatitis C virus (HCV) infection is determined by the interplay between the virus and the host immune response. Interleukin (IL)-18, an interferon-,-inducing factor, plays a critical role in the T helper type 1 (Th1) response required for host defence against viruses, and antibodies to IL-18 have been found to prevent liver damage in a murine model. The present study was conducted to investigate the possible role of IL-18 in the pathogenesis and persistence of HCV. IL-18 levels were measured in sera of 50 patients at various stages of HCV infection (resolved, chronic and cirrhosis) and compared with those of normal controls. IL-18 gene expression was studied in peripheral blood mononuclear cells (PBMC) from each group, and in liver biopsy tissue from patients with chronic hepatitis C. The mean levels of IL-18 in sera were markedly elevated in patients with chronic hepatitis and cirrhosis, and were reduced in patients with resolved HCV infection. The serum IL-18 concentrations were related to the Child,Pugh severity of liver disease in cirrhotic patients. There also existed a strong positive correlation of IL-18 levels with histological activity score and necrosis. IL-18 mRNA expression was significantly up-regulated in the PBMC of cirrhotic patients when compared with other groups, while in the liver, higher levels of IL-18 transcripts were expressed in patients with chronic hepatitis C. The results of our study indicate that IL-18 levels reflect the severity and activity of HCV infection, and may contribute to the pathogenesis and progression of liver disease associated with HCV. [source] H2-Dd -mediated upregulation of interleukin-4 production by natural killer T-cell and dendritic cell interactionIMMUNOLOGY, Issue 1 2008Kazuomi Mizuuchi Summary Natural killer T (NKT) cells are capable of subserving apparently opposite functions, the interferon-, (IFN-,)-mediated enhancement of host defence and interleukin-4 (IL-4) -mediated immune regulation. Although dendritic cells (DCs) potently activate NKT cells, DC regulation of the IL-4,IFN-, balance via NKT-cell activation is not well characterized. In the present study, we examined the effect of DC treatment with CpG oligodeoxynucleotide (ODN), a Toll-like receptor 9 ligand, on the induction of NKT-cell cytokine production. CpG-ODN-conditioned and ,-galactosylceramide (,-GalCer)-loaded myeloid DCs (CpG-DCs) from BALB/c mice showed enhanced ability to induce NKT-cell production of IL-4, but not IFN-,, compared to ,-GalCer-loaded control DCs (not treated with CpG-ODN). The CpG-DCs expressed significantly higher levels of H2-Dd than control DCs, and blocking of the H2-Dd and Ly49 receptor interaction during antigen presentation completely abolished the enhanced ability of the CpG-DCs to induce NKT-cell production of IL-4. These findings demonstrate that DC recognition of the CpG motif leads to induction of enhanced IL-4 production by NKT cells via interaction of the augmented H2-Dd with Ly49 receptors on NKT cells. [source] Detrimental role of endogenous nitric oxide in host defence against Sporothrix schenckiiIMMUNOLOGY, Issue 4 2008Karla Simone S. Fernandes Summary We earlier demonstrated that nitric oxide (NO) is a fungicidal molecule against Sporothrix schenckii in vitro. In the present study we used mice deficient in inducible nitric oxide synthase (iNOS,/,) and C57BL/6 wild-type (WT) mice treated with N,-nitro-arginine (Nitro-Arg-treated mice), an NOS inhibitor, both defective in the production of reactive nitrogen intermediates, to investigate the role of endogenous NO during systemic sporotrichosis. When inoculated with yeast cells of S. schenckii, WT mice presented T-cell suppression and high tissue fungal dissemination, succumbing to infection. Furthermore, susceptibility of mice seems to be related to apoptosis and high interleukin-10 and tumour necrosis factor-, production by spleen cells. In addition, fungicidal activity and NO production by interferon-, (IFN-,) and lipopolysaccharide-activated macrophages from WT mice were abolished after fungal infection. Strikingly, iNOS,/, and Nitro-Arg-treated mice presented fungal resistance, controlling fungal load in tissues and restoring T-cell activity, as well as producing high amounts of IFN-, Interestingly, macrophages from these groups of mice presented fungicidal activity after in vitro stimulation with higher doses of IFN-,. Herein, these results suggest that although NO was an essential mediator to the in vitro killing of S. schenckii by macrophages, the activation of NO system in vivo contributes to the immunosuppression and cytokine balance during early phases of infection with S. schenckii. [source] Response of lung ,, T cells to experimental sepsis in miceIMMUNOLOGY, Issue 1 2004Mark Hirsh Summary ,, T cells link innate and adaptive immune systems and may regulate host defence. Their role in systemic inflammation induced by trauma or infection (sepsis) is still obscured. The present study was aimed to investigate functions of lung ,, T cells and their response to experimental sepsis. Mice were subjected to caecal ligation and puncture (CLP) to induce sepsis and acute lung injury (ALI), or to the sham operation. Animals were killed 1, 4, and 7 days postoperatively; lungs were examined by histology, and isolated cells were studied by flow cytometry. Absolute number of ,, T cells progressively increased in lungs during sepsis, and reached a seven-fold increase at day 7 after CLP (3·84 ± 0·41 × 105/lung; P,=,0·0002 versus sham). A cellular dysfunction was revealed one day after CLP, as manifested by low cytolytic activity (22·3 ± 7·1%; P,<,0·05 versus sham), low interferon-, (IFN-,; 8·5 ± 2·5%; P,<,0·05 versus control) and interleukin-10 (IL-10) expression, and high tumour necrosis factor-, expression (19·5 ± 1·7%; P,<,0·05 versus control). The restoration of cytotoxicity, and increase in IFN-, and IL-10 expression was observed at day 7 of CLP-induced sepsis. In summary, our results demonstrate significant progressive accumulation of ,, T cells in lungs during CLP-induced ALI. The temporary functional suppression of lung ,, T cells found early after CLP may influence the outcome of sepsis, possibly being associated with uncontrolled inflammatory lung damage. [source] Cytotoxic T-cell responses to Mycobacterium bovis during experimental infection of cattle with bovine tuberculosisIMMUNOLOGY, Issue 2 2003Margot A. Skinner Summary Cytotoxic T-cell responses are thought to play a significant role in the host defence against mycobacterial infections. Little is understood about such responses of cattle to Mycobacterium bovis, the causative agent of bovine tuberculosis. The work described in this report demonstrates the activity of cytotoxic cells during experimental infection of cattle with M. bovis. The cytotoxic cells were found to have the ability to specifically lyse macrophages infected with M. bovis and were detected in peripheral blood lymphocytes after in vitro re-exposure to M. bovis. Cytotoxic activity was detected 4 weeks after experimental infection with M. bovis; a similar level of activity was maintained during the infection and it was mediated by both WC1+,, and CD8+ T cells. In addition, inhibition of the growth of M. bovis within infected macrophages was detected when they were exposed to cultures containing M. bovis -specific cytotoxic cells. The ability to detect cytotoxic cells after infection of cattle with M. bovis will allow their activity to be measured during vaccination trials. Correlation of cytotoxic activity with disease outcome may aid in the design of new vaccines and vaccination strategies. [source] Antimicrobial peptide mediators of host defence: bridges between the innate and adaptive phase of the immune responseIMMUNOLOGY, Issue 2002Article first published online: 9 DEC 200 First page of article [source] Innate immunity and systemic lupus erythematosusINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2006Ou JIN Abstract Innate immunity is the first-line host defence against pathogens and damaged host cells, and the major cellular components are phagocytes such as monocytes/macrophages, polymorphonuclear cells and dendritic cells. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the loss of tolerance to self-antigens, the source of which has been suggested to be apoptotic cells. In this article, we will review studies on apoptosis in SLE and discuss the contribution of innate immunity abnormalities in the development of this condition. [source] Effect of subtherapeutic concentrations of tylosin on the inhibitory stringency of a mixed anaerobe continuous-flow culture of chicken microflora against Escherichia coli O157:H7JOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2003T.L. Poole Abstract Aims: The aim of this study was twofold: first to determine the effect of subtherapeutic concentrations of tylosin, a macrolide antibiotic used for growth promotion, on a mixed anaerobic continuous-flow fermentation culture of chicken gastrointestinal microorganisms (CCF) and secondly, to determine if these concentrations would allow persistence of Escherichia coli O157:H7 in CCF. Methods and Results: CCF was treated with tylosin at 10·0, 20·0 and 40·0 ,g ml,1. Tylosin treatment resulted in a significant (P < 0·0001) decrease in total volatile fatty acids (VFAs) from a mean concentration of 101 ± 10·8 ,mol ml,1 in control cultures to 32·0 ± 6·3 and 40·2 ± 9·6 ,mol ml,1 in 10 and 40 ,g ml,1 treated cultures, respectively. Untreated CCF challenged with E. coli O157:H7 cleared the challenge microorganism in 7 days at a rate of 0·96 log10 CFU ml,1 day,1. In contrast, E. coli O157:H7 persisted in all tylosin treated cultures. Conclusions: In the presence of tylosin, E. coli O157:H7 was able to persist in the CCF culture. The significant decrease in the production of VFAs may have been a contributing factor. Significance and Impact of the Study: The use of low-level, growth-promoting antimicrobials may compromise the ability of normal microflora that serve as a natural host defence against infection. [source] Role of the innate immune system in host defence against bacterial infections: focus on the Toll-like receptorsJOURNAL OF INTERNAL MEDICINE, Issue 6 2007B. Albiger Abstract. The innate immunity plays a critical role in host protection against pathogens and it relies amongst others on pattern recognition receptors such as the Toll-like receptors (TLRs) and the nucleotide-binding oligomerization domains proteins (NOD-like receptors, NLRs) to alert the immune system of the presence of invading bacteria. Since their recent discovery less than a decade ago, both TLRs and NLRs have been shown to be crucial in host protection against microbial infections but also in homeostasis of the colonizing microflora. They recognize specific microbial ligands and with the use of distinct adaptor molecules, they activate different signalling pathways that in turns trigger subsequent inflammatory and immune responses that allows a immediate response towards bacterial infections and the initiation of the long-lasting adaptive immunity. In this review, we will focus on the role of the TLRs against bacterial infections in humans in contrast to mice that have been used extensively in experimental models of infections and discuss their role in controlling normal flora or nonpathogenic bacteria. We also highlight how bacteria can evade recognition by TLRs. [source] Function and therapeutic potential of host defence peptides,JOURNAL OF PEPTIDE SCIENCE, Issue 11 2005Joseph B. Mcphee Abstract Cationic host defence (antimicrobial) peptides are an important component of the innate immune systems of a wide variety of plants, animals, and bacteria. Although most of these compounds have direct antimicrobial activities under specific conditions, a greater appreciation for the diversity of functions of these molecules is beginning to develop in the field. In addition to their directly antimicrobial activities, they also have a broad spectrum of activity on the host immune system, with both pro-inflammatory and anti-inflammatory effects being invoked. Increasingly sophisticated approaches to understand the role of host defence peptides in modulating innate immunity are already serving to guide the development of novel therapeutics. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. [source] The RprY response regulator of Porphyromonas gingivalisMOLECULAR MICROBIOLOGY, Issue 4 2007Ana E. Duran-Pinedo Summary Porphyromonas gingivalis is a Gram-negative oral anaerobe associated with chronic adult periodontitis. Its ecological niche is the gingival crevice, where the organism adapts to the challenges of the infectious process such as host defence and bacterial products. Bacterial responses to environmental changes are partly regulated by two-component signal transduction systems. Several intact systems were annotated in the genome of P. gingivalis, as well as an orphan regulator encoding a homologue of RprY, a response regulator from Bacteroides fragilis. With the goal of defining the environmental cues that activate RprY in P. gingivalis, we used several strategies to identify its regulon. Results from gene expression and DNA,protein binding assays identified target genes that were either involved in transport functions or associated with oxidative stress, and indicated that RprY can act as an activator and a repressor. RprY positively activated the primary sodium pump, NADH : ubiquinone oxidoreductase (NQR), and RprY protein also interacted with the promoter regions of nqrA genes from B. fragilis and Vibrio cholerae. Given that gingival bleeding and infiltration of host defence cells are symptoms of periodontal infection, iron products released from blood and reactive oxygen species from polymorphonuclear leucocytes may be potential inducers of the RprY regulon. [source] Proteomic identification of peroxiredoxin 6 for host defence against Opisthorchis viverrini infectionPARASITE IMMUNOLOGY, Issue 5 2010J. KHOONTAWAD Summary Opisthorchis viverrini infection causes opisthorchiasis and is a risk factor for cholangiocarcinoma via chronic inflammation. To investigate the mechanism of O. viverrini -induced liver disease, we applied a proteomic approach to examine alterations in hepatic protein levels in O. viverrini -infected hamsters. Two-dimensional gel electrophoresis (2DE) revealed that O. viverrini infection induced upregulation (1·5- to 4·3-fold) of 25 proteins and downregulation (1·5 to 2·5-fold) of 24 proteins compared with uninfected animals. Expression of proteins related to stress response, DNA replication and repair, and cell structure was significantly increased, whereas that of proteins associated with normal liver function, such as metabolism, blood volume maintenance and fatty acid cycle was decreased. Among the upregulated proteins, a 2·7-fold increase in peroxiredoxin 6 (Prdx6), an antioxidant protein, was confirmed by 2DE and immunoblot analysis, Western blot and quantitative PCR. Immunohistochemical analysis showed that Prdx6 expression was observed mainly in the cytoplasm of inflammatory cells. These results suggest that Prdx6 is important for host defence against O. viverrini infection. This study provides basic information for Prdx6 as a potential biomarker and therapeutic target for opisthorchiasis. [source] Calpain-dependent cleavage of SHP-1 and SHP-2 is involved in the dephosphorylation of Jurkat T cells induced by Entamoeba histolyticaPARASITE IMMUNOLOGY, Issue 3 2010K. A. KIM Summary Host cell death induced by Entamoeba histolytica is an important mechanism for both host defence and microbial immune evasion during human amoebiasis. However, the signalling pathways underlying cell death induced by E. histolytica are not fully understood. This study investigated the involvement of the protein tyrosine phosphatases (PTPs) SHP-1 and SHP-2 in the dephosphorylation associated with E. histolytica -induced host cell death. Incubation with E. histolytica resulted in a marked decrease in protein tyrosine phosphorylation levels and degradation of SHP-1 or SHP-2 in Jurkat cells. Pre-treatment of cells with a calpain inhibitor, calpeptin, impeded the amoeba-induced dephosporylation and cleavage of SHP-1 or SHP-2. Additionally, inhibition of PTPs with phenylarsine oxide (PAO) attenuated Entamoeba -induced dephosphorylation and DNA fragmentation in Jurkat T cells. These results suggest that calpain-dependent cleavage of SHP-1 and SHP-2 may contribute to protein tyrosine dephosphorylation in Jurkat T cell death induced by E. histolytica. [source] Secretory antibodies against Giardia intestinalis in lactating Nicaraguan womenPARASITE IMMUNOLOGY, Issue 5 2005A. Téllez SUMMARY Secretory IgA (sIgA) antibodies are important in the host defence against the intestinal protozoan parasite Giardia intestinalis. However, few antigens have been identified. In this study 100 milk and saliva samples from lactating women, living in an endemic region (León, Nicaragua), were screened for the presence of antibodies against G. intestinalis. Most milk and saliva samples contained anti- Giardia antibodies (59% and 52%, respectively), with a mean sIgA content 50 times higher in milk than in saliva. The positive samples reacted with trophozoite membrane, flagella and cytoplasmic antigens. Western blot analysis showed that milk and saliva anti- Giardia sIgA recognized up to 16 different Giardia proteins in the molecular weight region 20,165 kDa. Two-dimensional Western blotting showed that the major immunoreactive proteins were the same as the immunoreactive proteins identified by serum from acute giardiasis patients in a non-endemic country. The major difference was a stronger reactivity against the variant surface proteins (VSPs) in the milk samples. Milk sIgAs also recognized recombinant Giardia proteins such as alpha-1 giardin, ornithine carbamoyl transferase, VSP-4EX, arginine deaminase and alpha-enolase. These antigens will be important targets in the development of new immunodiagnostic tools and vaccines. [source] Immune-mediated alteration in gut physiology and its role in host defence in nematode infectionPARASITE IMMUNOLOGY, Issue 8-9 2004W. I. Khan SUMMARY Activation of the mucosal immune system of the gastrointestinal tract in nematode infection results in altered intestinal physiology, which includes changes in intestinal motility and mucus production. These changes are considered to be under direct immunological control rather than a non-specific consequence of the inflammatory reaction to the infective agent. However, little is known about the immunological basis for the changes in intestinal physiology accompanying nematode infection, or the precise role of these changes in host defence, which remains an important area to explore. In this review we describe the mechanisms by which the immune response to nematode infection influences the changes in two major cells of intestinal physiology, namely smooth muscle and goblet cells, and how these changes in intestinal physiology contribute to the host defence. Data clearly demonstrate that the T helper (Th) 2 type immune response generated by nematode infection plays an important role in the development of infection-induced intestinal muscle hypercontractility and goblet cell hyperplasia and that these immune-mediated changes in intestinal physiology are associated with worm expulsion. These observations strongly suggest that intestinal muscle contractility, goblet cell hyperplasia and worm expulsion share a common immunological basis and may be causally related. These data not only provide insights into host defence in nematode infection in the context of muscle function and goblet cell response, but also have broad implications in elucidating the pathophysiology of a wide range of gastrointestinal disorders associated with altered gut physiology. [source] Interleukin-5 deficient mice exhibit impaired host defence against challenge Trichinella spiralis infectionsPARASITE IMMUNOLOGY, Issue 10 2000B.A. Vallance Enteric nematode infections are characterized by both peripheral and tissue eosinophilia. The cytokine interleukin (IL)-5 is considered a critical factor in the proliferation and recruitment of eosinophils, however, studies suggest it plays little role in host defence, at least during primary Trichinella spiralis infections. Less is known concerning its role in host defence or in the inflammatory response that develops against challenge infections with the same parasite. We examined these questions by infecting IL-5 deficient and wild-type mice, with T. spiralis parasites. Both strains expelled the primary infection by day 21. Forty days after the primary infection, we challenged the mice with a second T. spiralis infection and counted tissue eosinophils and worms in the intestine. While wild-type mice developed a large tissue eosinophilia, IL-5 deficient mice showed little increase in eosinophil numbers within the intestine. Throughout the challenge infection, significantly larger worm burdens were recovered from IL-5 deficient mice, and worm expulsion was also significantly slower (day 21) compared to wild-type mice (day 14). Thus, unlike in a primary infection, IL-5 is not only essential for the onset of intestinal eosinophilia, but also makes a significant contribution to enteric host defence during challenge T. spiralis infections. [source] Altered expression of antimicrobial molecules in cigarette smoke-exposed emphysematous mice lungsRESPIROLOGY, Issue 7 2008Yoko SHIBATA Background and objective: The natural history of COPD, a disease usually caused by cigarette smoking, is associated with frequent respiratory infections. Consistent with human COPD, bacterial clearance in the lungs has been reported to be impaired in mice exposed to cigarette smoke. In the airways, several antimicrobial molecules such as surfactant proteins (SP), beta-defensins (BD), secretory leucocyte protease inhibitor (SLPI) and lysozyme play important roles in the defence against invading pathogens. This study evaluated the expression of antimicrobial molecules in mice lungs with cigarette smoke-induced emphysematous changes. Methods: Six B6C3F1 mice were exposed to cigarette smoke (2 cigarettes/day/mouse for 6 months) or room air. Gene expression within the lungs of mice in both groups was assessed by RT-PCR. Results: The expression of SP-A, BD2, BD3 and SLPI was significantly elevated in the lungs of cigarette smoke-exposed mice compared with air-exposed mice. BD1 expression decreased in the smoke-exposed mice and lysozyme expression was unchanged. Conclusions: Chronic cigarette smoke exposure did not suppress the expression of antimicrobial molecules in the lung. Altered expression of antimicrobial molecules in this mouse model does not explain the impaired host defence against respiratory microbes seen in patients with COPD. [source] Coevolution of daily activity timing in a host,parasite systemBIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 2 2009IRENE ORTOLANI Coevolutionary theories applied in the study of host,parasite systems indicate that lineages exhibit progressive trends in response to reciprocal selective pressures. Avian brood parasites have generated intense interest as models for coevolutionary processes. Similar to avian cuckoos, Polistes wasp social parasites usurp a nest and exploit the parental care of a congeneric species to rear their own brood. In the present study, we show a coevolutionary arms race in the daily activity pattern in a Polistes host,parasite pair. We measured the daily activity rate, in constant laboratory conditions, of both host and parasite females during the period in which nest usurpations occur. The parasites showed a hyperkinesis in the middle of the day. As the field observations suggested, this mid-day activity is used to perform host nest usurpation attempts. Timing the usurpations allows the parasite to maximize its usurpation attempts during daytime when the host defence is lower. A field comparison of host presence on the nest in two populations with different parasitism rates showed that populations under strong parasitic pressure exhibit timing counteradaptations to optimize nest defence. This study provides the first example of a mutual coadaptation in timing activity in a parasite,host system. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 96, 399,405. [source] Role of cytokines of the tumour necrosis factor family in the immune response to disseminated Candida albicans infectionBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 7 2000M. G. Netea Background Tumour necrosis factor (TNF) ,, lymphotoxin (LT) ,, CD40L and FasL are members of the TNF family that play a crucial role in modulation of the immune response. Their role in the defence against infection with Candida albicans was investigated in mice deficient in either TNF-, and LT-, (TNF,/, LT,/, mice), CD40L (CD40L,/, mice) or Fas (MRL/lpr mice). Methods Mortality rates were compared in mice infected intravenously with 106 colony-forming units of C. albicans per mouse. Results After infection with C. albicans the TNF,/, LT,/, mice had a significantly increased mortality rate compared with control mice (100 versus 40 per cent; P < 0·01). This was due to a 10,1000-fold increased outgrowth of the yeasts in the kidneys and liver of TNF,/, LT,/, mice (P < 0·01). Defective recruitment and phagocytosis, but not Candida killing, were responsible for these effects. CD40L,/, mice were also more susceptible to systemic candidiasis than the wild-type controls (mortality rate 80 versus 50 per cent; P < 0·05), and the growth of Candida in the kidneys was one order of magnitude higher in the deficient than in control mice (P < 0·05). Neutrophil function in the CD40L,/, mice was normal, whereas decreased Candida killing by macrophages through nitric oxide-dependent mechanisms was responsible for the effect of CD40/CD40L interactions. In contrast, Fas-defective MRL/lpr mice were significantly more resistant to disseminated candidiasis (mortality rate 50 versus 100 per cent; P < 0·01); this was mediated by the facilitation of neutrophil migration to the site of infection. Conclusion Cytokines of the TNF family play a crucial role in the modulation of host defence against fatal C. albicans infection. Their effects are exerted selectively at the level of neutrophil or macrophage function. © 2000 British Journal of Surgery Society Ltd [source] Evasion of innate and adaptive immune responses by influenza A virusCELLULAR MICROBIOLOGY, Issue 7 2010Mirco Schmolke Summary Host organisms have developed sophisticated antiviral responses in order to defeat emerging influenza A viruses (IAVs). At the same time IAVs have evolved immune evasion strategies. The immune system of mammals provides several lines of defence to neutralize invading pathogens or limit their replication. Here, we summarize the mammalian innate and adaptive immune mechanisms involved in host defence against viral infection and review strategies by which IAVs avoid, circumvent or subvert these mechanisms. We highlight well-characterized, as well as recently described features of this intriguing virus-host molecular battle. [source] Scavenger receptors: role in innate immunity and microbial pathogenesisCELLULAR MICROBIOLOGY, Issue 8 2009Thomas Areschoug Summary Accumulating evidence shows that many scavenger receptors (SR), including SR-A, MARCO and CD36, represent an important part of the innate immune defence by acting as pattern-recognition receptors, in particular against bacterial pathogens. Several SR are expressed on macrophages and dendritic cells, where they act as phagocytic receptors mediating non-opsonic phagocytosis of pathogenic microbes. Another important function of some SR is to act as co-receptors to Toll-like receptors (TLR), modulating the inflammatory response to TLR agonists. On bacteria, the SR ligands have commonly been reported to be lipopolysaccharide and lipoteichoic acid, but recent advances in the field indicate that bacterial surface proteins play a more important role as target molecules for SR than previously thought. Interestingly, recent data show that major pathogens, including Streptococcus pyogenes and the group B streptococcus, have evolved mechanisms to evade SR-mediated recognition. Moreover, intracellular pathogens, such as hepatitis C virus and Plasmodium falciparum, utilize the SR to gain entry into host cells, focusing interest on the importance of SR also in the molecular pathogenesis of infectious diseases. This review highlights the complex interactions between SR and pathogenic microbes, and discusses the role of these interactions in host defence and microbial pathogenesis. [source] Role of haem oxygenase-1 in microbial host defenceCELLULAR MICROBIOLOGY, Issue 2 2009Su Wol Chung Summary Haem oxygenase (HO)-1 is a cytoprotective enzyme that plays a critical role in defending the body against oxidant-induced injury during inflammatory processes. HO catalydes the degradation of haem to carbon monoxide (CO), biliverdin and ferrous iron. Biliverdin is converted to bilirubin, a potent endogenous antioxidant. CO has a number of biological functions, including anti-inflammatory properties. In various models of disease, HO-1 is known to play a critical role by ameliorating the pathological consequences of injury. In many of these models, the beneficial effects of HO-1 and its products of haem catabolism are by suppressing an inflammatory response. However, when investigating diseases due to microbial infections, inhibition of the inflammatory response could disrupt the ability of the immune system to eradicate an invading pathogen. Thus, questions remain regarding the role of HO-1 in microbial host defence. This microreview will address our present understanding of HO-1 and its functional significance in a variety of microbial infections. [source] Streptococcus pyogenes induces oncosis in macrophages through the activation of an inflammatory programmed cell death pathwayCELLULAR MICROBIOLOGY, Issue 1 2009Oliver Goldmann Summary Macrophages are crucial components of the host defence against Streptococcus pyogenes. Here, we demonstrate the ability of S. pyogenes to kill macrophages through the activation of an inflammatory programmed cell death pathway. Macrophages exposed to S. pyogenes exhibited extensive cytoplasmic vacuolization, cellular and organelle swelling and rupture of the plasma membrane typical of oncosis. The cytotoxic effect of S. pyogenes on macrophages is mediated by the streptococcal cytolysins streptolysin S and streptolysin O and does not require bacterial internalization. S. pyogenes -induced death of macrophages was not affected by the addition of osmoprotectant, implicating the activation of an orchestrated cell death pathway rather than a simple osmotic lysis. This programme cell death pathway involves the loss of mitochondria transmembrane potential (,,m) and was inhibited by the addition of exogenous glycine, which has been shown to prevent necrotic cell death by blocking the opening of death channels in the plasma membrane. The production of reactive oxygen species and activation of calpains were identified as mediators of the cell death process. We conclude that activation of the inflammatory programmed cell death pathway in macrophages could constitute an important pathogenic mechanism by which S. pyogenes evades host immune defences and causes disease. [source] Bacterial exotoxins downregulate cathelicidin (hCAP-18/LL-37) and human ,-defensin 1 (HBD-1) expression in the intestinal epithelial cellsCELLULAR MICROBIOLOGY, Issue 12 2008Krishnendu Chakraborty Summary Cathelicidin (hCAP-18/LL-37) and ,-defensin 1 (HBD-1) are human antimicrobial peptides (AMPs) with high basal expression levels, which form the first line of host defence against infections over the epithelial surfaces. The antimicrobial functions owe to their direct microbicidal effects as well as the immunomodulatory role. Pathogenic microorganisms have developed multiple modalities including transcriptional repression to combat this arm of the host immune response. The precise mechanisms and the pathogen-derived molecules responsible for transcriptional downregulation remain unknown. Here, we have shown that enteric pathogens suppress LL-37 and HBD-1 expression in the intestinal epithelial cells (IECs) with Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) exerting the most dramatic effects. Cholera toxin (CT) and labile toxin (LT), the major virulence proteins of V. cholerae and ETEC, respectively, are predominantly responsible for these effects, both in vitro and in vivo. CT transcriptionally downregulates the AMPs by activating several intracellular signalling pathways involving protein kinase A (PKA), ERK MAPKinase and Cox-2 downstream of cAMP accumulation and inducible cAMP early repressor (ICER) may mediate this role of CT, at least in part. This is the first report to show transcriptional repression of the AMPs through the activation of cellular signal transduction pathways by well-known virulence proteins of pathogenic microorganisms. [source] Host,pathogen interplay and the evolution of bacterial effectorsCELLULAR MICROBIOLOGY, Issue 2 2008John Stavrinides Summary Many bacterial pathogens require a type III secretion system (T3SS) and suite of type III secreted effectors (T3SEs) to successfully colonize their hosts, extract nutrients and consequently cause disease. T3SEs, in particular, are key components of the bacterial arsenal, as they function directly inside the host to disrupt or suppress critical components of the defence network. The development of host defence and surveillance systems imposes intense selective pressures on these bacterial virulence factors, resulting in a host,pathogen co-evolutionary arms race. This arms race leaves its genetic signature in the pattern and structure of natural genetic variation found in T3SEs, thereby permitting us to infer the specific evolutionary processes and pressures driving these interactions. In this review, we summarize our current knowledge of T3SS-mediated host,pathogen co-evolution. We examine the evolution of the T3SS and the T3SEs that traverse it, in both plant and animal pathosystems, and discuss the processes that maintain these important pathogenicity determinants within pathogen populations. We go on to examine the possible origins of T3SEs, the mechanisms that give rise to new T3SEs and the processes that underlie their evolution. [source] | |||||||||||||||||||||||||||||||