解淀粉芽孢杆菌对巨噬细胞极化的影响及其信号通路解析

项目名称： 解淀粉芽孢杆菌对巨噬细胞极化的影响及其信号通路解析

项目编号： No.31472128

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 畜牧学与草地科学

项目作者： 李卫芬

作者单位： 浙江大学

项目金额： 85万元

中文摘要： 解淀粉芽孢杆菌SC06（Ba SC06）是一株由本课题组筛选的具提高动物免疫功能的益生菌，它对巨噬细胞M1极化的调节是其提高动物对病原菌的清除、发挥益生作用的重要原因之一。本项目拟通过体外培养小鼠原代骨髓源Mφ，研究Ba SC06对Mφ极化及其信号通路中关键转录因子（M1型为STAT1/2、NF-κB、AP1、IRF3、IRF5和IRF9，M2型为STAT3/6）磷酸化水平的影响，并通过抗体阻断技术验证Ba SC06介导Mφ极化的信号通路。随后通过小鼠体内试验，研究Ba SC06对正常小鼠和病原菌感染模型小鼠体内Mφ极化和肠粘膜免疫功能的影响，探明Ba SC06对体内Mφ极化的调控是否与机体免疫功能及对病原菌的清除力的提高直接相关；最后通过猪源Mφ细胞体外培养和仔猪饲养试验，进一步研究Ba SC06对猪Mφ极化、信号通路和肠粘膜免疫功能的影响。研究结果将为芽孢杆菌调节Mφ极机理的阐明提供理论基础。

中文关键词： 芽孢杆菌；巨噬细胞；极化；信号通路

英文摘要： Bacillus amyloliquefaciens SC06 (BaSC06), a strain of probiotic screened by our research group, has been proved to have remarkable effects on growth and immunity function of animals. M1 macrophage polarization mediated by BaSC06 may be one of. key mechnisms related to its beneficial effects, such as improving phagocytic capacity of animals. In order to examine whether macrophage polarization induced by BaSC06 is directly related to immunologic function and its resistance to pathogens, we will systematically study the influences of BaSC06 on macrophage polarization and the proteins phosphorylation levels of key transcriptional factors(STAT1/2、NF-κB、AP1、IRF3、IRF5 and IRF9 for M1， STAT3/6 for M2) by culturing BMDM in vitro. According to the results obtained, the signaling pathway involved in BaSC06-induced macrophage polarization is deduced , which is verified by antibody blocking experiment. After that, we will analyze the effect of BaSC06 on macrophage polarization and intestinal mucosal immune function of normal mice and infectious mice in vivo. Eventually, we will further test the importance of BaSC06 in porcine macrophage polarization, signaling pathway and intestinal mucosal immune function by porcine-originated macrophage in vitro experiments and piglets feeding trails. Results will provide theoretical basis for elucidating mechanism of macrophage polarization induced by BaSC06，and also supply the technique and theoretical guidance for BaSC06 applied in pig and feed industry.

英文关键词： Bacillus;macrophage;polarization;signaling pathway