结核杆菌蛋白Mce1F介导细菌免疫逃逸及新机制

结核病（TB）严重危害人类健康，宿主炎症应答是机体抗结核感染的关键，结核分枝杆菌（Mtb）如何调控炎症应答介导免疫逃逸是亟待解决的科学问题。申请人长期致力于Mtb-巨噬细胞相互作用的调控机制研究，原创性发现Mtb细胞壁蛋白Mce1F（Rv0174）具有介导细菌免疫逃逸的功能。预实验结果显示，Mce1F可能与清道夫受体Ssc5d结合，靶向TLR4-TRIF依赖的炎症信号通路介导免疫逃逸。本项目拟在已有研究的基础上，解析Mce1F与Ssc5d的相互作用，阐明Mce1F经Ssc5d调控TLR4-TRIF信号通路蛋白的翻译后修饰、蛋白稳定性及关键蛋白质机器的组装和功能。旨在揭示Mce1F介导免疫逃逸的新机制，为TB新型靶向药物的研制提供坚实的理论基础和数据支持。

Tuberculosis (TB) is a challenging problem which seriously endangers public health. Host inflammatory response exerts crucial function in combating Mycobacterium tuberculosis (Mtb) infection. It is important to resolve the mechanism of the Mtb immune evasion urgently. Applicant has devoted to the research of modulation mechanism between Mtb and macrophage. On this basis, the original discovery of the Mtb cell wall protein Mce1F (Rv0174), which has the capability to mediate bacterial immune evasion. Preliminary experimental results showed that Mce1F has a tendency to combine with scavenger receptor Ssc5d, regulating TLR4-TRIF-depenent inflammatory signaling pathway to mediate immune evasion.This project intends to analyse the interaction between Mce1F and Ssc5d, elucidates that Mce1F regulates the post-translational modification, protein stability, and protein-machine of TLR4-TRIF signaling pathway proteins through Ssc5d. It aims to reveal the new mechanism of Mce1F-mediated immune evasion and provide a solid theoretical basis and data support for the development of novel targeted drugs for TB.