结核菌（M. tb）胞壁脂糖与宿主细胞的相互作用介导了M. tb免疫逃逸的关键环节。B细胞作为宿主重要免疫细胞，它能直接识别脂糖，但其被M. tb脂糖调控的机制有待阐明。我们前期进行了M. tb 脂糖ManLAM（甘露糖修饰脂阿拉伯甘露聚糖）介导的免疫逃逸机制研究，报道了ManLAM能被宿主细胞MR（甘露糖受体）识别，并上调胞内脂糖代谢受体PPARgamma（过氧化物酶体增殖物激活受体gamma）表达。本项目在前期工作基础上，将ManLAM诱发B细胞脂代谢异常和细胞活化受阻联系起来，联合运用RNA转录组学、生物信息学以及体内外生物学实验，拟阐明ManLAM激活B细胞MR/TLR2通路、上调PPARgamma表达致胞内脂质蓄积的分子机制；进一步探讨脂质蓄积是否阻滞B细胞骨架重构和抑制BCR活化。以上研究将帮助明确M. tb脂糖介导的免疫逃逸机制，为寻找新结核病治疗靶点提供帮助。

The interaction between host cells and lipoglycans of Mycobacterium tuberculosis (M. tb) mediates the critical step of immune evasion by M. tb. B cells, an important component in immune system, directly recognize the lipoglycans. However, it remains unknown how B cells are regulated by M. tb lipoglycans. Mannosylated lipoarabinomannan (ManLAM) is a lipoglycan and major virulence factor in M. tb. We have been reported that ManLAM is recognized by mannose receptor (MR). The binding of MR to ManLAM upregulates the expression of peroxisome proliferator-activated receptor gamma (PPARgamma). In our current work, we plan to investigate the abnormal lipid metabolism and impairment of cell activation in B cells induced by ManLAM. Using combined analysis of RNA transcriptomics, bioinformatics and biological experiments, we plan to confirm that ManLAM-MR/TLR2 binding upregulates PPARgamma expression. The increased expression of PPARgamma in B cells results in lipid body formation. The lipid bodies inhibit the cytoskeletal rearrangement and BCR signaling. Our work will provide new information of M. tb. immune evasion and pathogenesis, and help to develop new therapeutic strategies in clinic.