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Innate Immune Defense (innate + immune_defense)
Selected AbstractsPlasmacytoid dendritic cell activation by foot-and-mouth disease virus requires immune complexesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2006Laurence Guzylack-Piriou Abstract Natural IFN-producing cells (NIPC), also called plasmacytoid dendritic cells, represent an essential component of the innate immune defense against infection. Despite this, not much is known about the pathways involved in their activation by non-enveloped viruses. The present study demonstrates that the non-enveloped foot-and-mouth disease virus (FMDV) cannot stimulate IFN-, responses in NIPC, unless complexed with FMDV-specific immunoglobulins. Stimulation of NIPC with such immune complexes employs Fc,RII ligation, leading to strong secretion of IFN-,. In contrast to the stimulation of NIPC by many enveloped viruses, FMDV induction of IFN-, production requires live virus. It is necessary for the virus to initiate its replicative cycle. Moreover, it is an abortive replication, as witnessed by the decrease of dsRNA levels and viral titers with time post infection. Sensitivity of the NIPC stimulation to wortmannin and chloroquin, but not leupeptin, indicates an essential role for the pre-lysosomal stage endosomal compartment. In conclusion, the present study demonstrates that immune complexes provide the means for a non-interferogenic virus to induce IFN-, responses by NIPC. This indicates an important link between NIPC and antibodies in immune responses against non-enveloped viruses such as FMDV. [source] ORIGINAL ARTICLE: Safety Analysis of the Diaphragm in Combination with Lubricant or Acidifying Microbicide Gels: Effects on Markers of Inflammation and Innate Immunity in Cervicovaginal FluidAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2009Deborah J. Anderson Objective, Diaphragms are being considered for use with vaginal microbicide gels to provide enhanced protection against sexually transmitted pathogens. The purpose of this study was to determine whether use of a diaphragm with microbicide or placebo gel causes cervicovaginal inflammation or perturbations in cervicovaginal immune defense. Method of study, Eighty-one non-pregnant women were randomized into three groups and instructed to use Milex® (CooperSurgical, Inc., Trumbull, CT, USA)diaphragms overnight for 14 days in combination with one of the two acid-buffering microbicide gels [ACIDFORMÔ (Instead Inc., La Jolla, CA, USA) or BufferGelÔ (BG; ReProtect Inc., Baltimore, Maryland)] or placebo gel (K-Y Jelly®; Personal Products Inc., Raritan, NJ, USA). Cervicovaginal lavages (CVLs) were performed prior to study entry and on days 8 and 16. Nine soluble mediators of vaginal inflammation or immune defense were measured in CVLs by Bio-Plex or ELISA. Results, Use of diaphragms with placebo or microbicide gel was not associated with increased levels of inflammation markers. Concentrations of secretory leukocyte protease inhibitor (SLPI) were markedly reduced in the BG group. Conclusion, Daily use of a diaphragm with placebo or acidifying microbicide gel did not cause cervicovaginal inflammation. However, diaphragm/BG use was associated with markedly reduced levels of SLPI, an important mediator of innate immune defense. Further studies are warranted to establish the safety of diaphragm/microbicide gel combinations. [source] Human Fallopian Tube Neutrophils , A Distinct Phenotype from Blood NeutrophilsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2006Jennifer M. Smith Problem, The role of neutrophils in the human Fallopian tube (FT) is unknown. In order to provide insights into their functions in the FT, we systematically compared neutrophils from normal FT and peripheral blood (PB). Method of study, Flow cytometric analysis of surface receptors, granule proteins, and intracellular cytokines expressed by neutrophils from enzymatically dispersed FT and PB was performed. Results, Fallopian tube neutrophils expressed significantly higher levels of CD64, human class II histocompatibility antigen DR (HLA-DR), , -interferon, and vascular endothelial growth factor than those from PB. Fewer FT neutrophils expressed IL-8 receptors compared to PB, while more expressed the receptor for the bacterial-derived chemoattractant formyl-Met-Leu-Phe (fMLP). The number of FT neutrophils containing the granule proteins matrix metalloproteinase-9, lactoferrin, and myeloperoxidase was decreased versus PB. Conclusion, Fallopian tube neutrophils exhibit a phenotype distinct from PB neutrophils, suggesting functional activation of innate immune defense in the female reproductive tract as well as a potential role in maintaining normal FT physiology. [source] RNA helicase encoded by melanoma differentiation,associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease,ARTHRITIS & RHEUMATISM, Issue 7 2009Shinji Sato Objective To identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C-ADM) and rapidly progressive interstitial lung disease (ILD). Methods An anti,CADM-140 antibody,positive prototype serum sample was used to screen a HeLa cell,derived complementary DNA (cDNA) library. Selected cDNA clones were further evaluated by immunoprecipitation of their in vitro,transcribed and in vitro,translated products using anti,CADM-140 antibody,positive and anti-CADM-140 antibody,negative sera. The lysates of COS-7 cells transfected with the putative antigen were similarly tested. An enzyme-linked immunosorbent assay (ELISA) to detect the anti,CADM-140 antibody was established using a recombinant CADM-140 antigen, and its specificity and sensitivity for C-ADM and rapidly progressive ILD were assessed in 294 patients with various connective tissue diseases. Results By cDNA library screening and immunoprecipitation of in vitro,transcribed and in vitro,translated products, we obtained a cDNA clone encoding melanoma differentiation,associated gene 5 (MDA-5). The anti,CADM-140 antibodies in patients' sera specifically reacted with MDA-5 protein expressed in cells transfected with full-length MDA-5 cDNA, confirming the identity of MDA-5 as the CADM-140 autoantigen. The ELISA, using recombinant MDA-5 protein as the antigen, showed an analytical sensitivity of 85% and analytical specificity of 100%, in comparison with the "gold standard" immunoprecipitation assay, and was useful for identifying patients with C-ADM and/or rapidly progressive ILD. Conclusion Given that RNA helicase encoded by MDA-5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C-ADM and rapidly progressive ILD. Moreover, our ELISA using recombinant MDA-5 protein makes detection of the anti,CADM-140 antibody routinely available. [source] Impaired expression and function of toll-like receptor 7 in hepatitis C virus infection in human hepatoma cells,HEPATOLOGY, Issue 1 2010Serena Chang Hepatitis C virus (HCV) interferes with interferon (IFN)-mediated innate immune defenses. Toll-like receptor (TLR) 7 agonists robustly inhibit HCV infection. We hypothesize that HCV infection may interfere with the expression and/or function of TLR7, a sensor of single-stranded RNA. We identified reduced TLR7 RNA and protein levels in hepatoma cells expressing HCV (full-length, BB7-subgenomic, and JFH-1 clone) compared with control HCV-naïve cells. The biological relevance of this finding was confirmed by the observation of decreased TLR7 RNA in livers of HCV-infected patients compared with controls. HCV clearance, by IFN-, treatment or restrictive culture conditions, restored the decreased TLR7 expression. Treatment with RNA polymerase inhibitors revealed a shorter TLR7 half-life in HCV-replicating cells compared with controls. Downstream of TLR7, an increased baseline IRF7 nuclear translocation was observed in HCV-positive cells compared with controls. Stimulation with the TLR7 ligand R837 resulted in significant IRF7 nuclear translocation in control cells. In contrast, HCV-replicating cells showed attenuated TLR7 ligand-induced IRF7 activation. Conclusion: Reduced TLR7 expression, due to RNA instability, directly correlates with HCV replication and alters TLR7-induced IRF7-mediated cell activation. These results suggest a role for TLR7 in HCV-mediated evasion of host immune surveillance. (HEPATOLOGY 2009.) 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