Immunologic receptor

Abstract: We recently demonstrated that the beta-glucan receptor Dectin-1 (betaGR) was the major nonopsonic beta-glucan receptor on macrophages (Mphi) for the yeast-derived particle zymosan However, on resident peritoneal Mphi, we identified an additional mannan-inhibitable receptor for zymosan that was distinct from the Mphi mannose receptor (MR) In this study, we have studied the mannose-binding potential of murine Mphi and identified the dendritic cell-specific ICAM-3-grabbing nonintegrin homolog, SIGN-related 1 (SIGNR1), as a major MR on murine resident peritoneal Mphi Both SIGNR1 and betaGR cooperated in the nonopsonic recognition of zymosan by these Mphi When SIGNR1 was introduced into NIH3T3 fibroblasts or RAW 2647 Mphi, it conferred marked zymosan-binding potential on these cells However, in the nonprofessional phagocytes (NIH3T3), SIGNR1 was found to be poorly phagocytic, suggesting that other receptors such as betaGR may play a more dominant role in particle internalization on professional phagocytes Binding of zymosan to RAW 2647 Mphi expressing SIGNR1 resulted in TNF-alpha production Treatment of RAW 2647 Mphi expressing SIGNR1, which express low levels of betaGR, with beta-glucans had little effect on binding or TNF-alpha production, indicating that there was no absolute requirement for betaGR in this process These studies have identified SIGNR1 as a major MR for fungal and other pathogens present on specific subsets of Mphi

Abstract: Background: Irritable bowel syndrome (IBS) is largely viewed as a stress-related disorder caused by aberrant brain-gut– immune communication and altered gastrointestinal (GI) homeostasis. Accumulating evidence demonstrates that stress modulates innate immune responses; however, very little is known on the immunological effects of stress on the GI tract. Toll-like receptors (TLRs) are critical pattern recognition molecules of the innate immune system. Activation of TLRs by bacterial and viral molecules leads to activation of NF-kB and an increase in inflammatory cytokine expression. It was our hypothesis that innate immune receptor expression may be changed in the gastrointestinal tract of animals with stressinduced IBS-like symptoms. Methodology/Principal Findings: In this study, our objective was to evaluate the TLR expression profile in the colonic mucosa of two rat strains that display colonic visceral hypersensivity; the stress-sensitive Wistar-Kyoto (WKY) rat and the maternally separated (MS) rat. Quantitative PCR of TLR2-10 mRNA in both the proximal and distal colonic mucosae was carried out in adulthood. Significant increases are seen in the mRNA levels of TLR3, 4 & 5 in both the distal and proximal colonic mucosa of MS rats compared with controls. No significant differences were noted for TLR 2, 7, 9 & 10 while TLR 6 could not be detected in any samples in both rat strains. The WKY strain have increased levels of mRNA expression of TLR3, 4, 5, 7, 8, 9 & 10 in both the distal and proximal colonic mucosa compared to the control Sprague-Dawley strain. No significant differences in expression were found for TLR2 while as before TLR6 could not be detected in all samples in both strains. Conclusions: These data suggest that both early life stress (MS) and a genetic predisposition (WKY) to stress affect the expression of key sentinels of the innate immune system which may have direct relevance for the molecular pathophysiology of IBS.

Abstract: The means by which a unique lymphokine imparts to macrophages the capacity to ingest complement- (C) coated particles was explored. In contrast to other previously described lymphokines that influence macrophage behavior, the T cell product that enhances macrophage C receptor function was found to act immediately upon contact with macrophages and to be of substantially lower apparent m.w. than either MIF, MAF, lymphotoxin, or interferon. Evidence is presented that indicates that the lymphokine does not act by causing a generalized increase in plasma membrane phagocytic activity or by enhancing phagocytosis mediated by other immunologic receptors. Nor does the lymphokine act by inducing the synthesis of new protein receptors. Our findings suggest that the more likely possibilities by which the lymphokine acts include induction of an increased rate of insertion of C receptors into the macrophage plasma membrane, induction of a rearrangement of C receptors within the macrophage plasma membrane, or a qualitative alteration of the function of existing macrophage C receptors in their relationship with the intracellular machinery involved in phagocytosis.