Regulation of intestinal barrier by E. coli curli fibrils

描述（由申请方提供）：类淀粉是细菌生物膜的常见组分，由拟杆菌门、厚壁菌门和变形菌门的成员产生。 最近，我们已经表明，curli，一种在肠道细菌生物膜内发现的淀粉样蛋白，通过Toll样受体2（TLR 2）/TLR 1复合物被先天免疫系统识别。E.大肠杆菌Nissle 1917（Nissle）是由陆军外科医生Alfred Nissle博士从一名士兵的粪便中分离出来的，该士兵在第一次世界大战期间严重的志贺氏菌爆发期间没有腹泻。从那时起，许多研究调查了这种生物体用于益生菌治疗的潜在用途 炎症性肠病（IBD） 临床试验表明，EcN治疗在预防溃疡性结肠炎（UC）复发方面与标准药物一样有效。 随后的研究发现，尼氏能增强肠上皮屏障功能。 此外，Nissle对TLR 2的激活已显示在胃肠道中具有免疫调节作用。 然而，EcN诱导后者影响的机制仍然未知。 本申请的目的是研究细菌淀粉样蛋白对宿主肠道免疫应答的贡献。 我们推测，通过TLR 2在胃肠道中检测细菌淀粉样蛋白，使上皮细胞能够作为细菌从肠腔移位的哨兵，并通过增强上皮屏障来响应。我们将测试这一假设，通过研究的免疫调节功能的卷曲纤维所产生的微生物尼氏。

DESCRIPTION (provided by applicant): Amyloids, a common component of the biofilms of bacteria, are produced by the members of Bacteriodetes, Firmicutes and Proteobacteria. Recently, we have shown that curli, an amyloid found within the biofilms of enteric bacteria, is recognized by the innate immune system through Toll-like receptor 2 (TLR2)/TLR1 complex. E. coli Nissle 1917 (Nissle) was isolated by the army surgeon Dr. Alfred Nissle from the feces of a soldier who did not develop diarrhea during a severe Shigella outbreak during World War I. Since then many studies investigated the potential use of this organism for probiotic therapy in Inflammatory Bowel Diseases (IBD). Clinical trials have shown that treatment with EcN was as efficient as the standard medication in preventing the relapse of Ulcerativ Colitis (UC). Following studies have discovered that Nissle reinforces the intestinal epithelial barrier function. Furthermore, TLR2 activation by Nissle has been shown to have immunomodulatory effects in the gastrointestinal tract. Nonetheless, the mechanisms by which EcN induces the latter affects remain unknown. The objective of this application is to investigate the contribution of bacterial amyloids to host intesinal immune responses. We hypothesize that the detection of bacterial amyloids via TLR2 in the gastrointestinal tract enables epithelial cells to serve as sentinels for bacterial translocation fom the gut lumen and respond by augmenting the epithelial barrier. We will test this hypothesis by studying the immunomodulatory function of curli fibrils produced by the commensal organism Nissle.