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Host Immune Response (host + immune_response)
Selected AbstractsThermal biology of the meadow grasshopper, Chorthippus parallelus, and the implications for resistance to diseaseECOLOGICAL ENTOMOLOGY, Issue 6 2005Simon Springate Abstract., 1.,The thermal biology of the meadow grasshopper, Chorthippus parallelus, a common, habitat generalist acridid species found in the U.K., was characterised and the influence of thermoregulatory behaviour for resistance against a temperate (Beauveria bassiana) and tropical (Metarhizium anisopliae var. acridum) fungal pathogen was determined. 2.,Chorthippus parallelus was found to be an active behavioural thermoregulator, with a preferred temperature range of 32,35 °C. 3.,Both pathogens proved lethal to fifth instar and adult grasshoppers. No evidence of behavioural fever in response to infection by either pathogen was found, but normal thermoregulation was found to reduce virulence and spore production of B. bassiana. Normal thermoregulation did not appear to affect M. anisopliae var. acridum. 4.,These results suggest that the effects of temperature on host resistance depend on the thermal sensitivity of the pathogen and, in this case, derive from direct effects of temperature on pathogen growth rather than indirect effects mediated by host immune response. 5.,The implications for possible risks of exotic pathogens and influence of climate change are discussed. [source] CTL quality and the control of human retroviral infectionsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2009Charles R. M. Bangham Abstract The CTL response plays a central part in deciding the outcome of viral infections. Evidence from host and viral genetics, gene expression microarrays and assays of T-cell phenotype and function indicate that individual differences in the efficiency of the virus-specific CTL response strongly determine the outcome of infection with the human retroviruses HTLV-1 and HIV-1. It is now believed that differences in anti-viral CTL efficiency or "quality" at the single-cell level are critical in determining the efficacy of the host response to viruses. However, it is difficult to identify and quantify the reasons for this apparent individual variation in CTL efficiency, because of the chronic course of infection and the dynamical complexity of the equilibrium that is established between the virus and the host immune response. Specifically, it is unclear whether the observed variations among infected hosts, i.e. in the frequency, phenotype and function or quality of T cells, are the causes or effects , or both , of the variation in the efficiency of virus control. [source] Virulence factor p60 of Listeria monocytogenes modulates innate immunity by inducing tumor necrosis factor ,FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2010Hiroshi Sashinami Abstract We investigated the effect of p60, a virulence factor of Listeria monocytogenes, on host immune response in vitro and in vivo. Administration of p60 before a sublethal infection with L. monocytogenes enhanced innate host resistance in naďve mice. Mouse macrophage RAW264.7 cells produced tumor necrosis factor (TNF)-, in response to stimulation with recombinant p60. Toll-like receptor 4 may be involved in TNF-, production from RAW264.7 cells and enhanced host resistance induced by p60 administration. Our findings demonstrated that p60 modulates innate immune responses against L. monocytogenes infection. [source] Helicobacter pylori, T cells and cytokines: the "dangerous liaisons"FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2005Mario Milco D'Elios Abstract Helicobacter pylori infection is the major cause of gastroduodenal pathologies, but only a minority of infected patients develop chronic and life threatening diseases, as peptic ulcer, gastric cancer, B-cell lymphoma, or autoimmune gastritis. The type of host immune response against H. pylori is crucial for the outcome of the infection. A predominant H. pylori -specific Th1 response, characterized by high IFN-,, TNF-,, and IL-12 production associates with peptic ulcer, whereas combined secretion of both Th1 and Th2 cytokines are present in uncomplicated gastritis. Gastric T cells from MALT lymphoma exhibit abnormal help for autologous B-cell proliferation and reduced perforin- and Fas,Fas ligand-mediated killing of B cells. In H. pylori -infected patients with autoimmune gastritis cytolytic T cells infiltrating the gastric mucosa cross-recognize different epitopes of H. pylori proteins and H+K+ ATPase autoantigen. These data suggest that peptic ulcer can be regarded as a Th1-driven immunopathological response to some H. pylori antigens, whereas deregulated and exhaustive H. pylori -induced T cell-dependent B-cell activation can support the onset of low-grade B-cell lymphoma. Alternatively, H. pylori infection may lead in some individuals to gastric autoimmunity via molecular mimicry. [source] Association of immunological disorders in lethal side effect of NSAIDs on ,-glucan-administered miceFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2001Hideaki Takahashi Abstract (1,3)-,- d -Glucan (,-glucan) is a biological response modifier that regulates host immune response. We have found that the combination of a ,-glucan and a non-steroidal anti-inflammatory drug (NSAID), indomethacin (IND), induced lethal toxicity in mice [Yoshioka et al. (1998) FEMS Immunol. Med. Microbiol., 21, 171,179]. This study was undertaken to analyze the mechanism of the lethal side effect. Combination of a ,-glucan and IND increased the number of leukocytes, especially macrophages and neutrophils, in various organs and these cells were activated. The activated state of these cells was supported by the enhanced production of interferon-, in the presence of IND in vitro culture of the peritoneal exudate cells. Intestinal bacterial flora was translocated into the peritoneal cavity in these mice to cause peritonitis. Comparing the toxicity of various NSAIDs, nabumetone, a partially cyclooxygenase-2-selective NSAID with weaker toxicity to the gastrointestinal tract, did not exhibit a lethal side effect. These facts strongly suggested that gastrointestinal damage by NSAIDs was more severe in ,-glucan-administered mice, resulting in peritonitis by enteric bacteria and leading to death. [source] Hepatitis C virus quasispecies in the natural course of HCV-related disease in patients with haemophiliaHAEMOPHILIA, Issue 1 2004G. Tagariello Summary., Patients with haemophilia show high prevalence of hepatitis C infection but low rate of progressive liver disease when they are not co-infected with HIV. The balance between host immune system and hepatitis C virus (HCV) variability seems to play a major role in the evolution of the HCV-related disease. To address this point we have studied, in a group of selected patients with haemophilia, the composition and in some cases the evolution, of the highest variable envelope gene within the hypervariable region 1 (HVR1) of the HCV, which is the region more directly exposed to the host immune response. Five of 12 patients show a very high homogeneity of the HVR1 and four of those had severe progressive liver disease. These results seem to confirm the major role of the immunity in driving the variability of the HCV rather than the high degree of different HCV strains to which haemophiliacs have been in touch with, during their long-term replacement therapy. Our results seem in keeping with other studies on different type of patients, where a low degree of quasispecies variability has been demonstrated in relationship with the progression and the severity of their liver disease. [source] Role of Immune Serum in the Killing of Helicobacter pylori by MacrophagesHELICOBACTER, Issue 3 2010Stacey Keep Abstract Background:,Helicobacter pylori infection can lead to the development of gastritis, peptic ulcers and gastric cancer, which makes this bacterium an important concern for human health. Despite evoking a strong immune response in the host, H. pylori persists, requiring complex antibiotic therapy for eradication. Here we have studied the impact of a patient's immune serum on H. pylori in relation to macrophage uptake, phagosome maturation, and bacterial killing. Materials and Methods:, Primary human macrophages were infected in vitro with both immune serum-treated and control H. pylori. The ability of primary human macrophages to kill H. pylori was characterized at various time points after infection. H. pylori phagosome maturation was analyzed by confocal immune fluorescence microscopy using markers specific for H. pylori, early endosomes (EEA1), late endosomes (CD63) and lysosomes (LAMP-1). Results:, Immune serum enhanced H. pylori uptake into macrophages when compared to control bacteria. However, a sufficient inoculum remained for recovery of viable H. pylori from macrophages, at 8 hours after infection, for both the serum-treated and control groups. Both serum-treated and control H. pylori phagosomes acquired EEA1 (15 minutes), CD63 and LAMP-1 (30 minutes). These markers were then retained for the rest of an 8 hour time course. Conclusions:, While immune sera appeared to have a slight positive effect on bacterial uptake, both serum-treated and control H. pylori were not eliminated by macrophages. Furthermore, the same disruptions to phagosome maturation were observed for both serum-treated and control H. pylori. We conclude that to eliminate H. pylori, a strategy is required to restore the normal process of phagosome maturation and enable effective macrophage killing of H. pylori, following a host immune response. [source] CD8+ T-cell interaction with HCV replicon cells: Evidence for both cytokine- and cell-mediated antiviral activityHEPATOLOGY, Issue 6 2003Chen Liu The interaction between the host immune response and infected hepatocytes plays a central role in the pathogenesis of hepatitis C virus (HCV). The lack of a suitable animal or in vitro model has hindered our understanding of the host T-cell/HCV interaction. Our aim was to develop an in vitro model to study the mechanisms of HCV-specific T-cell-mediated antiviral and cytolytic function. The HCV replicon was HLA typed and lymphocytes were obtained from an HLA class I-matched subject. CD8+ T cells were expanded with 2 HCV-specific/HLA-restricted peptides for NS3. Lymphocyte preparations were cocultured with HCV replicon (FCA1) and control (Huh7) cells labeled with 51Cr. After a 48-hour incubation, the cells were harvested for RNA extraction. Standard blocking assays were performed in the presence of anti-interferon gamma (IFN-,), anti-tumor necrosis factor , (TNF-,), and anti-FasL. Cytolytic activity was measured by 51Cr release. HCV replicon cells express homozygous HLA-A11 alleles and present HCV nonstructural proteins. HCV-specific expansion of CD8+ cells led to a 10-fold decrease in HCV replication by Northern blot analysis and 21% specific lysis of FCA1 cells (compared with 2% of control Huh7 cells). Twenty percent of this antiviral activity was independent of T-cell binding, suggesting cytokine-mediated antiviral activity. The CD8+ antiviral effect was markedly reduced by blocking either IFN-, or FasL but was unaffected by blocking TNF-,. In conclusion, HCV-specific CD8+ cells inhibit viral RNA replication by cytokine-mediated and direct cytolytic effects. This T-cell/HCV subgenomic replicon system represents a model for the investigation of CD8 cell interaction with HCV-infected hepatocytes. [source] Human cytomegalovirus and natural killer-mediated surveillance of HLA class I expression: a paradigm of host,pathogen adaptationIMMUNOLOGICAL REVIEWS, Issue 1 2001Miguel López-Botet Summary: Among various strategies to evade the host immune response, some viruses like human cytomegalovirus (HCMV) interfere with surface MHC class I expression and antigen presentation to T lymphocytes. The ability of natural killer (NK) cells to detect MHC class I molecules through inhibitory receptors can be envisaged as an adaptation of the immune system for responding to such pathological alterations. To fulfil that role, rodents use members of the Ly49 C-type lectin superfamily, whereas primates employ killer immunoglobulin-like receptors and the immunoglobulin-like transcript 2/leucocyte immunoglobulin-like receptor-1 receptor. CD94/NKG2 lectin-like heterodimers represent the most conserved receptor system for MHC class I molecules; by interacting with human HLA-E or murine Qa-1b, CD94/NKG2A inhibitory receptors broadly probe the biosynthesis pathway of other class I molecules. Reciprocally, HCMV has developed mechanisms to evade the NK response while modulating HLA class Ia expression. The ability of HCMV to maintain surface levels of HLA-E and to express an HLA class I surrogate (UL18) are herein discussed in the context of the interplay with human NKR systems. This work was supported by grants FIS 00/0181 and SAF98-0006. We thank Dr A. Angulo for helpful discussion. [source] Interferon-, priming is involved in the activation of arginase by oligodeoxinucleotides containing CpG motifs in murine macrophagesIMMUNOLOGY, Issue 1pt2 2009Miriam V. Liscovsky Summary Recognition of microbial products by macrophages (M,) stimulates an inflammatory response and plays a critical role in directing the host immune response against infection. In the present work, we showed for the first time that synthetic oligodeoxynucleotides containing unmethylated cytosine guanine motifs (CpG) are able to stimulate, in the presence of interferon-, (IFN-,), both arginase and inducible nitric oxide synthase (iNOS) in murine M,. Unexpectedly, IFN-,, a cytokine believed to be an inhibitor of arginase activity, intervened in the activation of this enzyme. A significant increase in arginase activity was observed upon a short pre-incubation (1 hr) with IFN-, and subsequent CpG stimulation. Therefore, a very interesting observation of this study was that the CpG-mediated arginase activity is dependent on IFN-, priming. The increase in arginase activity as a result of stimulation with CpG plus IFN-,was correlated with augmented expression of the arginase II isoform. The use of pharmacological specific inhibitors revealed that arginase activity was dependent on p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK), but independent of c-Jun N-terminal kinase (JNK) activation. This report reveals a singular effect of the combination of CpG and IFN-,, one of the mayor cytokines produced in response to CpG administration in vivo. [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] Hepatitis B and C virus infection in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2001Dr. Livia Biancone Abstract Patients with Crohn's disease (CD) are at higher risk of hepatitis C (HCV) and B virus (HBV) infection, because of surgical and/or endoscopic procedures. However, the prevalence of HCV and HBV infection in CD is unknown. This issue may be relevant because of the growing use of immunomodulatory drugs in CD. The purpose of this study was to assess, in a multicenter study, the prevalence and risk factors of HCV and HBV infection in CD. The effect of immunomodulatory drugs for CD on the clinical course of hepatitis virus infections and of interferon-, (IFN-,) on the course of CD was examined in a small number of patients. Sera from 332 patients with CD and 374 control subjects (C) were tested for the following: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), HBcAb, HBeAg, HBeAb, anti-HCV, and HCV-RNA. An additional 162 patients with ulcerative colitis (UC) were tested as a disease control group. Risk factors were assessed by multivariate statistical analysis. Infection by either HCV or HBV was detected in 24.7% of patients with CD. In the age groups younger than 50 years, HCV prevalence was higher in CD than in C (p = 0.01). HCV infection in CD was associated with surgery (OR 1.71; 95% CI 1.00,2.93; p = 0.04), blood transfusions (OR 3.39; 95% CI 1.04,11.04; p = 0.04), and age (OR 2.3; 95% CI 1.61,3.56; p < 0.001). The event CD-related surgery appeared to be the main risk factor for HCV infection in CD. HCV prevalence was higher in CD (7.4%) than in UC (0.6%) (p = 0.001). HBcAb positivity was higher in CD (10.9%) and UC (11.5%) than in C (5.1%) (CD vs. C: p = 0.016; UC vs. C: p = 0.02), associated with age (OR 2.08; 95% CI 1.37,3.17; p = 0.001) and female gender (OR 2.68; 95% CI 1.37,3.17; p = 0.001) in CD and to UC duration (OR 1.20; 95% CI 1.06,1.36; p = 0.002). Immunomodulatory drugs did not influence the course of HBV or HCV infection in seven patients with CD, and IFN-, for chronic hepatitis C did not affect CD activity in six patients with CD. It is concluded that HBV prevalence is higher in CD than in C at all ages, whereas HCV prevalence is increased in young patients with CD, because of a greater need for surgery. The higher HCV (but not HBV) prevalence in CD than in UC suggests that the host immune response may influence the risk of HCV infection. Although a relatively high proportion of patients with CD showed HBV and/or HCV infections, this should not influence treatment strategies for CD. [source] Cutaneous leishmaniasis reactivation 2 years after treatment caused by systemic corticosteroids , first reportINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 6 2007Felipe Francisco Tuon MD American tegumentary leishmaniasis (ATL), an endemic anthropozoonosis in various countries in the world, is caused by parasites of the genus Leishmania. Despite reports on ATL reactivation as a result of immunosuppression, to the best of our knowledge, this paper describes the first case of ATL reactivation in its localized form (cutaneous leishmaniasis) associated with the administration of systemic corticosteroids. The possible action of corticosteroids on the host immune response to the parasite in patients with localized cutaneous leishmaniasis is discussed. This report demonstrates the possibility of ATL reactivation in patients using corticosteroids, an observation that should be considered in individuals treated with this medication. [source] Gamma,delta T cell subsets are differentially associated with granuloma development and organization in a bovine model of mycobacterial diseaseINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2009Brandon L. Plattner Summary The characteristic lesion in bovine tuberculosis is well-organized respiratory granulomas. This is typically associated with a strong T-helper 1 biased cell-mediated immune response and eventual containment of the infection. In bovine paratuberculosis, the classic lesion is unorganized granulomatous intestinal inflammation. Clinical paratuberculosis is associated with a T-helper 2 biased humoral immune response and eventual death because of inability of the host to contain the infection. Recent reports have suggested that gamma,delta (,,) T cells play a significant role in granuloma development and/or maintenance during initial stages of infection and may influence the subsequent adaptive immune response. The objective of this study was to use an in vivo bovine model to evaluate ,, T cells during the early host immune response to mycobacterial infection. We used immunofluorescent staining, hyperspectral microscopy, and computerized assisted morphometry to evaluate staining and distribution of ,, T cells during development of organized and unorganized granulomas. Our data suggest that bovine ,, T cell subsets are differentially recruited to early infection sites, and may be instrumental during the initial antimycobacterial host immune response as well as for granuloma organization. [source] Viral appropriation of apoptotic and NF-,B signaling pathwaysJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2004Andrew G. Bowie Abstract Viruses utilize a variety of strategies to evade the host immune response and replicate in the cells they infect. The comparatively large genomes of the Orthopoxviruses and gammaherpesviruses encode several immunomodulatory proteins that are homologous to component of the innate immune system of host cells, which are reviewed here. However, the viral mechanisms used to survive host responses are quite distinct between these two virus families. Poxviruses undergo continuous lytic replication in the host cytoplasm while expressing many genes that inhibit innate immune responses. In contrast, herpesviruses persist in a latent state during much of their lifecycle while expressing only a limited number of relatively non-immunogenic viral proteins, thereby avoiding the adaptive immune response. Poxviruses suppress, whereas latent gammaherpesviruses activate, signaling by NF-,B, yet both viruses target similar host signaling pathways to suppress the apoptotic response. Here, modulation of apoptotic and NF-,B signal transduction pathways are examined as examples of common pathways appropriated in contrasting ways by herpesviruses and poxviruses. © 2004 Wiley-Liss, Inc. [source] Origin of cardiac progenitor cells in the developing and postnatal heartJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2010Elizabeth N. Kuhn The mammalian heart lacks the capacity to replace the large numbers of cardiomyocytes lost due to cardiac injury. Several different cell-based routes to myocardial regeneration have been explored, including transplantation of cardiac progenitors and cardiomyocytes into injured myocardium. As seen with cell-based therapies in other solid organ systems, inherent limitations, such as host immune response, cell death and long-term graft instability have hampered meaningful cardiac regeneration. An understanding of the cell biology of cardiac progenitors, including their developmental origin, lineage markers, renewal pathways, differentiation triggers, microenvironmental niche, and mechanisms of homing and migration to the site of injury, will enable further refinement of therapeutic strategies to enhance clinically meaningful cardiac repair. J. Cell. Physiol. 225: 321,325, 2010. © 2010 Wiley-Liss, Inc. [source] Genetic characterization of complex inter-recombinant HIV-1 strains circulating in Spain and reliability of distinct rapid subtyping tools,JOURNAL OF MEDICAL VIROLOGY, Issue 3 2008Africa Holguín Abstract Genetic recombination and high rate of mutation increase HIV-1 diversity, allowing viruses to escape more easily from the host immune response or antiretroviral drugs. The recombinant nature of full-length HIV-1 genomic sequences derived from viruses infecting five epidemiologically unlinked individuals carrying HIV-1 non-B variants was investigated. Overlapping PCR amplifications followed by direct sequencing of viral products derived from plasma and phylogenetic analyses were carried out. Four viral sequences clustered with CRF06_cpx and one with CRF02_AG. However, subtyping of separate genes within the same genome revealed that four were recombinant forms involving different subtypes and/or CRFs with distinct breakpoints. Two specimens included CRF02_AG and CRF06_cpx sequences with several fragments from other HIV-1 clades along their genomes. Three rapid subtyping tools (Stanford, NCBI, and REGA) showed discrepant results when interpreting these viral sequences. This is the first description of CRF02_AG/CRF06_ cpx recombinants in Spain. The results highlight the tremendous heterogeneity of HIV-1 recombinant strains currently in circulation. J. Med. Virol. 80:383,391, 2008. © 2008 Wiley-Liss, Inc. [source] STAT1 and STAT3 ,/, splice form activation predicts host responses in mouse hepatitis virus type 3 infectionJOURNAL OF MEDICAL VIROLOGY, Issue 3 2003Qin Ning Abstract Signal transducer and activator of transcription 1, (STAT1 ,) is reported to be essential for IFN-, and IFN-, regulated gene expression, while STAT1 ,, an alternate splice-form, mediates only IFN-,-dependent gene expression. STAT3 , and STAT3 , splice forms are also differentially activated in response to cytokines including IL-6 and IL-10. The aim of this study was to investigate whether the STAT activation will predict the host immune response to viral infection and possibly a therapeutic target for the treatment of viral infection. Mouse hepatitis virus type 3 (MHV-3) resistant strain (A/J) and sensitive mouse strains (BalB/cJ) were infected intraperitoneally (i.p.) with 100 plaque form units (pfu) of MHV-3. The mice were sacrificed at the indicated times, and livers and spleens were immediately frozen in liquid nitrogen. Nuclear extracts proteins were detected by immunoblotting. STAT1 and STAT3 activation in spleen increased 24 to 72 hr following MHV-3 infections in both sensitive and resistant mouse strains. However, over this time period, the ratio of activated , to , splice-form for STAT1 and STAT3 increased above 1.0 in resistant A/J mice, while the ratio fell to <0.3 in MHV-3 sensitive Balb/cJ and C3H/HeJ strains. Activated STAT1 ,/, and STAT3 ,/, ratio in liver were similar in resistant and sensitive mouse strains. Treatment of sensitive Balb/cJ mice with neutralizing anti-TGF-, antibody could increase the STAT1 ,/, ratio to <1.0 in spleens, predicting enhanced rates of survival. These results suggested that ratio of activated STAT1 ,/, and STAT3 ,/, in mixed leukocytes from spleen predict the outcome to MHV-3 infection, and may be an important marker and therapeutic target for modification of host immune response to virus infection. J. Med. Virol. 69:306,312, 2003. © 2003 Wiley-Liss, Inc. [source] Hepatitis viruses: live and let dieLIVER INTERNATIONAL, Issue 3 2007K. Herzer Abstract Viral hepatitis is a diffuse inflammatory reaction of the liver caused by hepatotropic viruses. Among the hepatitis viruses, only hepatitis B virus and hepatitis C virus are able to persist in the host and cause chronic hepatitis. In the course of persistent infection, inflammation forms the pathogenetic basis of chronic hepatitis that can lead to nodular fibrosis, which can progress to cirrhosis and, eventually, hepatocellular carcinoma (HCC). Of the different antiviral defense systems employed by the host, apoptosis significantly contributes to the prevention of viral replication, dissemination, and persistence. Pathomorphologic studies have shown acidophilic bodies and hepatocyte dropout, features that are compatible with apoptosis. The number of hepatocytes showing features of apoptosis in patients with chronic hepatitis B and C was found to be higher than in healthy subjects, indicating that apoptosis is involved in the pathogenesis of these diseases. There are various data suggesting that hepatitis B and C viral proteins may modulate apoptosis. Vice versa, mechanisms of apoptosis inhibition might represent central survival strategies employed by the virus which, in the end, may contribute to HCC development. While the expression and retention of viral proteins in hepatocytes may influence the severity and progression of liver disease, the mechanisms of liver injury in viral hepatitis are defined to be due not only to the direct cytopathic effects of viruses, but also to the host immune response to viral proteins expressed by infected hepatocytes. However, the exact role of these observations in relation to pathogenesis remains to be established. The mechanism and systems are complex. This report aims to provide an overview and intends to cite only a small number of pertinent references. [source] Differential expression of toll-like receptor mRNA in treatment non-responders and sustained virologic responders at baseline in patients with chronic hepatitis CLIVER INTERNATIONAL, Issue 9 2006Qi He Abstract: Background/Aims: The contribution of the host immune response to sustained virologic response is not clear in patients with chronic hepatitis C (CHC). The aim of this study was to explore the relationship of the toll-like receptor (TLR) expression with the outcome of antiviral therapy in hepatitis C viral infection. Methods: Peripheral blood mononuclear cells (PBMC) were obtained from 15 CHC patients before a 48-week treatment with pegylated interferon (PEG IFN) ,-2a and ribavirin. A multiplex semi-quantitative reverse-trancriptase polymerase chain reaction (RT-PCR) was used to compare the relative abundance of TLR2,9 transcripts. Results: mRNA levels of TLR2, 3 and 6 were significantly higher in CHC subjects compared with normal controls (n=8). When patients were classified into non-responders (n=8) and sustained virological responders (n=7) according to the virological outcome of the treatment, there was a clear difference in baseline mRNA expression of TLRs and T-helper (Th) 1/2 cytokines. In addition, the mRNA expression of IFN-, and nuclear factor of activated T cells (NFAT), which is exclusively expressed in activated T cells, was inversely correlated with that of TLR4, 6 and 9 in non-responders. Conclusions: TLRs mRNA levels are differentially expressed in baseline PBMC of chronic HCV-infected subjects with or without responsiveness to antiviral therapy. [source] Cell wall ,-1,3-glucan is required to anchor the Cryptococcus neoformans capsuleMOLECULAR MICROBIOLOGY, Issue 4 2003Amy J. Reese Summary Cryptococcus neoformans is an opportunistic pathogen responsible for serious disease in humans. Critical for virulence of this fungus is an elaborate polysaccharide capsule, which impedes the host immune response. We found that association of the capsule with the cell requires a specific component of the cell wall, ,-1,3-glucan. Post-transcriptional inhibition of ,-1,3-glucan synthase expression, using double-stranded RNA interference, yields cells that are unable to assemble a capsule although they generate its polysaccharide components. The resulting cryptococci are slow-growing and acapsular. This finding demonstrates a novel mode of polysaccharide attachment and an important application of RNA interference in fungi. The elimination of the capsule by reducing the expression of a single gene suggests a potential avenue for antifungal chemotherapy. [source] Inhibition of interferon-,-induced nitric oxide production in endotoxin-activated macrophages by cytolethal distending toxinMOLECULAR ORAL MICROBIOLOGY, Issue 5 2008K. P. S. Fernandes Introduction:, Cytolethal distending toxin (CDT) is a DNA-targeting agent produced by certain pathogenic gram-negative bacteria such as the periodontopathogenic organism Aggregatibacter actinomycetemcomitans. CDT targets lymphocytes and other cells causing cell cycle arrest and apoptosis, impairing the host immune response and contributing to the persistence of infections caused by this microorganism. In this study we explored the effects of CDT on the innate immune response, by investigating how it affects production of nitric oxide (NO) by macrophages. Methods:, Murine peritoneal macrophages were stimulated with Escherichia coli sonicates and NO production was measured in the presence or not of active CDT. Results:, We observed that CDT promptly and significantly inhibited NO production by inducible nitric oxide synthase (iNOS) in a dose-dependent manner. This inhibition is directed towards interferon-,-dependent pathways and is not mediated by either interleukin-4 or interleukin-10. Conclusion:, This mechanism may constitute an important aspect of the immunosuppression mediated by CDT and may have potential clinical implications in A. actinomycetemcomitans infections. [source] Expression of MHC Class II, CD70, CD80, CD86 and pro-inflammatory cytokines is differentially regulated in oral epithelial cells following bacterial challengeMOLECULAR ORAL MICROBIOLOGY, Issue 6 2003D. C. Han Oral epithelium may play a regulatory role in local immune responses when interacting with bacteria. The present study was undertaken to investigate the effects of selected bacterial pathogens found in periodontal and endodontic infections on oral epithelial cells. Expression of cell surface molecules (major histocompatibility complex (MHC) Class II, CD54, CD70, CD80 and CD86) and secretion of inflammatory cytokines (interleukin (IL)-1,, IL-6, and tumor necrosis factor (TNF)-,) in response to selected bacterial challenge were examined on an immortalized oral epithelial cell line, HOK-18A and a skin epithelial cell line, HaCaT. Actinomyces viscosus, Actinomyces israelii, Fusobacterium nucleatum lipopolysaccharide (LPS) or primary human periradicular exudate from a granuloma were co-cultured with epithelial cells for 4 or 24 h. Subsequently, cell surface expression of MHC Class II, CD54, CD70, CD80 and CD86, along with pro-inflammatory cytokine levels were determined using flow cytometry, ELISA and RT-PCR. Results indicated that the selected oral bacteria have greater effects on oral versus skin epithelial cells. F. nucleatum increased MHC Class II and CD54 (ICAM-1) cell surface expression on HOK-18A and HaCaT cells. A. israelii also had enhancing effects on the expression of CD54 and MHC Class II. A. israelii and LPS induced a 2.8-fold (P < 0.001) and 4.4-fold (P < 0.005) TNF-, secretion, respectively, while F. nucleatum and LPS induced a 10-fold (P < 0.0004) and 6-fold (P < 0.01) IL-1, secretion, respectively by HOK-18A. Interestingly, CD70, CD80, and CD86 were generally decreased upon bacteria and LPS challenge on HOK-18A. The effects of increased MHC Class II and decreased CD70 were also evident with challenge of human periradicular exudate on HOK-18A. The implications of the study are unique in that oral epithelial cells may play both activating and inhibitory roles in the host immune response towards infection by oral bacteria. We introduce a concept of ,dormancy' where the differential expression of key cell surface antigens on oral epithelial cells may keep the recruited immune effector cells in a state of unresponsiveness, thus contributing to the long term quiescent period observed in many periodontal and endodontic lesions. [source] Characterization of inflammatory cells in oral paracoccidioidomycosisORAL DISEASES, Issue 4 2007E Kaminagakura Paracoccidioidomycosis (Pmycosis) is one of the most common deep mycoses in many regions of Latin America, particularly in Brazil. Microscopically, it shows granulomatous inflammatory reaction with giant cells, macrophages, lymphocytes, plasma cells, polymorphonuclear neutrophilic leukocytes, and eosinophils. The purpose of this study was to assess the distribution of inflammatory cells in oral Pmycosis. Fifteen cases of oral Pmycosis were studied by immunohistochemistry for the presence of macrophages, CD4+ and CD8+ lymphocytes, CD20+, CD15+, and S100+ cells. Macrophages were the main cells in well-organized granulomas and non-granulomatous areas. The CD4 phenotype was predominant in well-organized granulomas and a balance between CD4+ and CD8+ cells was observed in non-granulomatous areas. Dendritic, S100+ cells were found mainly in the epithelium, in subepithelial connective tissue, and at the periphery of organized granulomas. CD15+ cells were concentrated mainly in areas of intraepithelial microabscess and ulceration. Macrophages and T cells are the predominant cells in oral Pmycosis. Well-organized granulomas contain fewer yeast particles, indicating a more effective host immune response. Better understanding of the histopathological changes in oral Pmycosis might help determine treatment, severity and systemic involvement of the disease. [source] The immunology of susceptibility and resistance to scabiesPARASITE IMMUNOLOGY, Issue 8 2010S. F. WALTON Summary The transmission of scabies occurs with the burrowing of Sarcoptes scabiei var. hominis mites into the skin. Infestation invariably leads to the development of localized cutaneous inflammation, pruritis and skin lesions. Classical transmission studies document an initial increase in S. scabiei numbers subsequent to primary infestation with a gradual reduction as host immunity develops. However, certain individuals fail to control infection and develop severe crusting of the skin, accompanied with extremely high mite burdens, elevated antibody levels and eosinophilia. These individuals have the nonhealing form of the human disease known as crusted scabies. The genetic predisposition for susceptibility or resistance to S. scabiei infection in humans is hypothesized to correlate with the dominance of an IgE-driven Th2 response in severe disease or an interferon-,-dominated Th1 response that promotes parasite control. However, recent data reveals complexities in cytokine regulation in the skin and the mechanisms of acquired resistance and immune escape. In this review, we consider the recent immunological and biomolecular advances in understanding the human host immune response to S. scabiei infestations in the context of earlier studies and attempt to reconcile apparent differences and emphasize those aspects of the Th1/Th2 model that are supported or refined. [source] Comparison of immune responses in mice infected with different strains of Strongyloides venezuelensisPARASITE IMMUNOLOGY, Issue 11 2007E. R. MACHADO SUMMARY In human hosts and in murine models, the immune response to Strongyloides spp. is Th2 type. In addition, the profile of the host immune response follows various symptoms induced by Strongyloides spp. In the present study, we demonstrated that the L2 and L49 strains of Strongyloides venezuelensis obtained from Bolomys lasiurus and Nectomys squamipes induced significant and similar increases in eosinophil/mononuclear cell counts in the blood, peritoneal cavity fluid and bronchoalveolar lavage fluid when compared with uninfected mice. However, in the first 3 days of infection, IL-4, IL-5 and IFN-, levels were higher in the lungs of mice infected with the L2 strain, which also presented greater production of IgG and IgG1 than did mice infected with the L49 strain. The higher antibody and cytokine levels induced by the L2 strain correlated with a decrease in the number of female parasites recovered in the faeces of mice on post-infection day 7. The results demonstrate that the L2 strain was a more potent stimulant of the humoral immune response, which can result in more efficient antibody-dependent cell-mediated cytotoxicity, a mechanism involved in eosinophil activation and parasite elimination. Further studies are needed in order to elucidate the molecular differences among parasites. [source] The immune response during a Strongyloides ratti infection of ratsPARASITE IMMUNOLOGY, Issue 7 2007C. P WILKES SUMMARY A range of immune parameters was measured during a primary infection of Strongyloides ratti in its natural rat host. The immune parameters measured were interleukin-4 (IL-4) and interferon-, from both the spleen and mesenteric lymph node (MLN) cells; parasite-specific immunoglobulin G1(IgG1), IgG2a and IgG2b in serum and in intestinal tissue; parasite-specific IgG and total IgE in serum; parasite-specific and total IgA in intestinal tissue and rat mast cell protease II in intestinal tissue. Parasite-specific IgG1, IgG2a and total IgE in serum and parasite-specific IgA and rat mast cell protease II in intestinal tissue all occurred at significantly greater concentrations in infected animals, compared with non-infected animals. Similarly, the production of IL-4 by MLN cells stimulated with parasitic female antigen or concanavalin A occurred at significantly greater concentrations in infected animals, compared with non-infected animals. In all, this suggests that there is a T-helper 2-type immune response during a primary S. ratti infection. These data also show the temporal changes in these components of the host immune response during a primary S. ratti infection. [source] Molluscan and vertebrate immune responses to bird schistosomesPARASITE IMMUNOLOGY, Issue 7-8 2005P. HORÁK SUMMARY There is a growing understanding of risks posed by human contact with the cercariae of bird schistosomes. In general, there are no fundamental biological differences between human and bird schistosomes in terms of their interactions with snail and vertebrate hosts. The penetration of host surfaces is accompanied by the release of penetration gland products and the shedding of highly antigenic surface components (miracidial ciliated plates and cercarial glycocalyx) which trigger host immune reactions. New surface structures are formed during transformation: the tegument of mother sporocysts and the tegumental double membrane of schistosomula. These surfaces apparently serve as protection against the host immune response. Certain parasite excretory,secretory products may contribute to immunosuppression or, on the other hand, stimulation of host immune reactions. Discovery of new species and their life cycles, the characterization of host,parasite interactions (including at the molecular level), the determination of parasite pathogenicity towards the host, the development of tools for differential diagnosis and the application of protective measures are all topical research streams of the future. Regularly updated information on bird schistosomes and cercarial dermatitis can be found at http://www.schistosomes.cz (web pages of Schistosome Group Prague). [source] Malignant Melanoma Associated with Lichen Sclerosus in the Vulva of a 10-Year-OldPEDIATRIC DERMATOLOGY, Issue 4 2004Ashraf M. Hassanein M.D., Ph.D. Lichen sclerosus of the vulva in childhood is also a rare disease. The association of these two rare lesions in the vulva of young girls is extremely rare. We present a 10-year-old white girl with malignant melanoma associated with lichen sclerosus of the vulva. She had dark pigmentation of both the labia minora and posterior fourchette. The inner labia majora and fourchette showed whitish, glistening areas of skin. Histologic examination found mostly an in situ lentiginous/mucosal melanoma with focal invasion to a depth of 0.44 mm in the left upper labium majus. All specimens showed evidence of lichen sclerosus. Partial vulvectomy was performed, and no metastases were detected at the time of treatment. The patient has been disease free for the 12 months after treatment. It is critical for physicians to realize that melanoma can occur in children, and although rare, can occur in the vulva. We feel that lichen sclerosus in this instance may represent a pattern of host immune response to melanoma. [source] Interleukin-1,, interleukin-6 and tumor necrosis factor-, levels in children with sepsis and meningitisPEDIATRICS INTERNATIONAL, Issue 2 2006NADIA M. FIDA Abstract Background: Cytokines are thought to be important endogenous mediators of the host immune response to infection. The purpose of the present study was to evaluate the utility of serum levels of interleukin (IL)-1,, IL-6 and tumor necrosis factor (TNF)-, in the prediction and differentiation of sepsis and meningitis in children. Methods: Blood was collected from 50 children admitted to hospital for suspicion of infection. On the basis of predetermined criteria and investigation, the children were classified into sepsis (n = 30) and meningitis (n = 20) groups, as well as into healthy controls (n = 24) and non-infected sick controls (n = 12). The sepsis group was subdivided according to culture results into S1 (proven sepsis, n = 11) and S2 (clinical sepsis, n = 19). Serum IL-1,, IL-6 and TNF-, were measured by enzyme-linked immunosorbent assay (ELISA) while C-reactive protein (CRP) was measured by nephelometer. Results: In non-infected sick controls, sepsis and meningitis groups, levels of CRP (P < 0.001, P < 0.05 and P < 0.01, respectively), IL-1, (P < 0.001 for all), and IL-6 (P < 0.01, P < 0.001, P < 0.001, respectively) were significantly elevated compared to healthy controls. In sepsis, levels of IL-1, increased in the S2 subgroup (P < 0.001) and IL-6 increased in the S1 and S2 subgroups (P < 0.05, P < 0.001, respectively) compared with healthy controls. In meningitis, IL-1, had the highest sensitivity and negative predictive value, while IL-6 had the highest specificity and positive predictive value in non-infected sick controls, sepsis and meningitis groups. Conclusion: Interleukin-1,, IL-6 and CRP are increased in non-infected sick controls, sepsis and meningitis patients but it is not possible to differentiate between them. IL-1, had the highest sensitivity in meningitis while IL-6 had the highest specificity in prediction of sepsis and meningitis and their assessment together may improve accuracy in the diagnosis of childhood infection. [source] | |||||||||||||||||||||||||||||||||||||