共生菌与免疫的关系解析.ppt

肠道是病原体常入侵的部位 病原体跨越肠道上皮细胞屏障的机制： - 通过M细胞转运 - 上皮细胞胞内入侵 - 通过上皮细胞层的破口 肠道细胞表达的PRR: - 细胞内PRR: NOD1 (许多类性细胞表达，检测内毒素）以及NOD2 (主要由巨噬细胞表达，也可检测胞内PAMPs)。 - TLR-5在上皮细胞基底面表达，可与已经跨越上皮屏障细菌的鞭毛素结合。 - TLR-4是在炎症存在下表达于上皮细胞的腔面。 * * Figure 1 | The gut microbiota-mediated development of the intestinal immune system. a | Segmented filamentous bacteria (SFB) and other commensal microorganisms activate lamina propria dendritic cells (DCs) and macrophages to induce T helper 17 (TH17) cells and TH1 cells through the production of interleukin?1β (IL?1β), IL?6 and IL?23 in the case of TH17 cells, and possibly IL?12 in the case of TH1 cells (although the role of IL-12 in TH1 development in vivo in the gut remains to be confirmed). TH17 cells regulate the gut microbiota community in an IL?22-and regenerating islet-derived protein 3γ (REGIIIγ)-dependent manner. Clostridium spp. clusters IV and XIVa, polysaccharide A (PSA)+ Bacteroides fragilis and other microbiota stimulate intestinal epithelial cells, T?cells, and lamina propria DCs and macrophages to promote the development and/or the activation of forkhead box P3 (FOXP3)+ regulatory T (TReg) cells. b | The microbiota stimulates intestinal epithelial cells and DCs to promote IgA-producing B?cell and plasma cell differentiation in the lamina propria. Toll-like receptor (TLR) activation on intestinal epithelial cells induces the secretion of B?cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), which promote the differentiation of IgA-producing plasma cells. Intestinal epithelial cells also produce thymic stromal lymphoprotein (TSLP) to promote BAFF and APRIL expression by DCs. Various types of DCs, such as plasmacytoid DCs (pDCs), TIP DCs (TNF and inducible nitric oxide synthase (iNOS)-producing DCs) and TLR5+ DCs secrete BAFF, APRIL, nitric oxide (NO), retinoic acid and tumour necrosis factor (TNF) to facilitate the expression of activation-induced cytidine deaminase (AID) and IgA class-switching in