结核分枝杆菌感染宿主后可逃逸机体免疫系统的监视和清除而得以在巨噬细胞中长期存活，但其分子机制尚未完全明确。深入研究结核分枝杆菌入侵巨噬细胞及其在胞内存活的分子机制，对于阐明结核病的发病机制以及探寻抗结核新药靶具重要意义。以往研究提示：结核分枝杆菌的mce3操纵子可能与结核分枝杆菌入侵宿主细胞及胞内存活相关，但其编码的某些单个蛋白（如Mce3C）的确切功能和作用机制尚不清楚。在本项目中，我们拟综合应用生化与分子生物学、细胞生物学和免疫学等方法和技术确证Mce3C在结核分枝杆菌入侵宿主巨噬细胞及胞内存活过程中的功能。我们还将鉴定与Mce3C互作的宿主蛋白分子，并探寻Mce3C通过与特定宿主分子间相互作用进而调控宿主的细胞骨架重排、炎症免疫相关信号通路、凋亡和自噬等方面的功能及机制。该研究将有助于进一步揭示结核分枝杆菌潜伏感染和致病的分子机制，还将为抗结核药物研发提供新的策略和和靶标。

Mycobacterium. tuberculosis can escape from immune surveillance and clearance so as to survive in host macrophage cells for long periods of time, but the underlying molecular mechanisms remain largely unknown. It is of great importance to investigate the molecular mechanisms underlying the invasion and intracellular survival of M. tuberculosis in macrophage cells to gain a better understanding of the pathogenesis of tuberculosis, as well as to identify novel anti-tuberculosis drug targets. Previous studies have suggested that the third operon of mammalian cell entry (mce3) from M. tuberculosis might play an important role in cell entry and intracellular survival of M. tuberculosis, but the specific function of certain individual proteins encoded by this operon (such as Mce3C) and the detailed regulatory mechanisms of them remain undefined. In this project, we will apply multiple methodologies and techniques of biochemistry and molecular biology, cell biology, and immunology into the investigation of the function of Mce3C during the invasion and intracellular survival of M. tuberculosis in macrophage cells. We will further identify Mce3C-interacting host molecules and elucidate their regulatrory roles in cellular functions such as cytoskeleton rearrangement, inflammation and immune response-associated signaling pathways, apoptosis and autophagy. This project would shed light on the molecular mechanisms of latent infection and pathogenesis of M. tuberculosis. It would also provide novel strategies and targets for the development of anti-tuberculosis drugs.