泛素连接酶TRAF2通过调控NF-kB信号通路影响结核分枝杆菌在巨噬细胞中存活的分子机制研究

Latent infection of Mycobacterium tuberculosis (Mtb) is the essential pathogenetic foundation of tuberculosis and the key factor for the difficulty in treating it. Studies have shown that virulent Mtb can escape the killing from macrophages via modulating the activity of NF-kB signaling pathway in host cells. Therefore, to explore the key molecules in this modulatory process is important for understanding the molecular mechanisms of Mtb infection. E3 ubiqutin ligase TRAF2 is a crucial adapter molecular regulating the NF-kB signaling pathway at upstream, thus TRAF2 might be an important host molecule interfering with the Mtb infection. Therefore, in this project, we sought to: 1) confirm whether TRAF2 is involved in the process of Mtb infection and survival via regulating the NF-kB signaling pathway; 2) further explore the molecular mechanisms of the above process. This study will provide novel knowledge about how the eukaryotic Ubiquitin-Proteasome pathway is involved in the host defense mechanism during Mtb infection and also reveal new strategies and molecular targets for the development of novel anti-tuberculosis drugs.

结核分枝杆菌（Mtb）在宿主中的潜伏感染是其致病的重要基础，也是造成结核病难治的关键因素之一。研究表明Mtb强毒株可以通过影响宿主细胞内的NF-kB信号通路，抑制巨噬细胞凋亡而发生免疫逃逸。因此，探寻该过程中关键的调控分子对于了解Mtb在宿主细胞内存活的分子机制具有重要意义。泛素连接酶TRAF2是真核细胞内一个重要的衔接分子，在NF-kB信号通路的上游起到调节分选作用，极有可能是影响Mtb在巨噬细胞中存活的重要宿主分子。因此在本项目中，我们拟：1）确认TRAF2是否参与Mtb感染宿主细胞的过程；2）深入探讨TRAF2通过调节NF-kB信号通路参与Mtb在巨噬细胞内存活的分子机制。该研究将为了解真核细胞泛素蛋白酶体如何参与Mtb感染中宿主的自我防御机制提供新的理论知识，为研制新的抗结核药物提供新思路和分子靶标。