乳酸菌介导RegIIIγ/MyD88分子调节宿主肠道空间结构稳定及免疫应答的分子机制研究

Lactic acid bacteria has many prebiotic functions to maintain intestinal microecological balance ,but how to maintain lactobacillus in space with hosts on the stable without ausing potentially harmful immune response? The project has intended to use Balb/c mice with Lactic acid bacteria and detected of expression quantity of RegⅢγ in small intestine, the immunology index of mucosal surface and luminal ，to confirm that Lactic acid bacteria has promoted the amount of RegⅢγ on the Small intestinal epithelial surface , leading to bacterial colonization of the intestinal epithelial cell surface increasing , as well as microbial-induced intestinal immune responses enhancing. In conclusion, the results of this study will reveal that the Lactic acid bacteria induce host innate mucosal immune mechanism through RegⅢγ expression.

乳酸菌具有维持肠道微生态平衡等诸多益生功能，但乳酸菌如何维持与宿主之间空间上的稳定且不引起潜在的有害免疫应答？本项目拟使用Balb/c小鼠，服用乳酸后，通过检测小肠中RegⅢγ的表达量，黏膜表面和管腔中的免疫学指标，证实乳酸菌引发肠上皮细胞表面RegⅢγ表达量增多，以及微生物引发的肠道免疫应答反应增强。本研究结果将初步探索乳酸菌通过调节RegⅢγ分子诱导宿主先天黏膜免疫机制。

定植于肠道中的微生物与宿主存在一种互惠共生关系，肠道屏障中RegIIIγ所形成的无菌区是维持其稳态的关键。本研究发现SPF 级Balb/c小鼠口服灌胃乳酸菌后小肠与结肠中RegIIIγ表达水平显著升高；细胞因子MyD88与Th17都有表达，但MyD88表达非常显著；肠系膜淋巴结、PP结及脾脏中树突状细胞MHCⅡ、CD11b+、CD103+、CD11c+仅在高剂量灌胃混合乳酸菌时能够活化和启动肠道固有层中的树突状细胞。结果表明乳酸菌主要通过MyD88途径特异性诱导肠上皮细胞表面RegIIIγ的产生和表达量增多，进而引发肠道免疫应答反应增强，使肠道内环境动态平衡更具缓冲力。为下一步探索乳酸菌如何维持与宿主之间空间结构上的稳定和调节RegⅢγ分子诱导宿主先天黏膜免疫机制的深入研究做了充足的理论和试验基础。