牛磺脱氧胆酸通过调节非折叠蛋白反应增强自噬促进胞内类鼻疽菌清除的作用机制研究

病原菌和宿主的相互作用是决定其感染和发病的前提。内质网应激作为自噬的诱导信号，是机体适应性免疫的重要组成部分，在抗病原菌感染和维持细胞稳态中发挥重要作用。类鼻疽菌作为一种正在扩散的热带医学传染病病原，严重威胁人类健康和公共卫生，其胞内寄生逃避宿主免疫特性造成潜伏感染及播散成为类鼻疽治疗的关键。类鼻疽菌感染显著增强细胞的内质网应激（非折叠蛋白反应UPR增强），同时自噬受到明显抑制，病原得以在胞内生存增殖并通过MNGC形成导致感染扩散。牛磺脱氧胆酸可以通过抑制UPR提高内质网处理蛋白能力，效应蛋白CHOP表达减少，伴侣分子Bip表达增加，有效促进自噬，有利于细菌的清除，具体机制有待阐明。本项目拟通过类鼻疽菌感染细胞和动物模型，研究牛磺脱氧胆酸通过调节UPR增强自噬促进胞内类鼻疽菌清除的作用及机制，以期阐明内质网应激在类鼻疽菌胞内感染与致病的机理，为寻找抗类鼻疽感染的有效治疗方案提供理论指导。

The interaction of bacterial pathogen and host is the premise of its infection and pathogenesis. Endoplasmic reticulum stress (ERS), as a vital part of cellular adaptive immune and a signal of autophagy induction, plays an important role in anti- infection and cell homeostasis. Burkholderia pseudomallei is a spreading tropical agent and a serious threat to human body and public health, while its ability to evade the host immune results into its latent infection anddissemination which become a key of melioidosis treatment. After infection, ERS/UPR (unfolded protein response) was induced dramatically in accompany of autophagy inhibition followed the replication of the pathogen and cell fusion. However, inhibition of UPR could induce autophagy for better elimination of intercellular bacterial, and the machanism behind is little known. This study aims to figure out the machanism UPR inhibitor (taurodeoxycholic acid) benefits to the clearance of intercellular Burkholderia pseudomallei by enhancing autophagy and the theoretical basis of new method for anti-Burkholderia pseudomallei.