Department of Epidemiology, Fourth Military Medical University, 17 Changle West Road, Xi'an, Shaanxi Province, China.
DNA Cell Biol. 2012 Feb;31(2):171-9. doi: 10.1089/dna.2011.1290. Epub 2011 Jul 8.
Autophagy plays specific roles in host innate and adaptive immune responses to numerous intracellular pathogens, including Mycobacterium tuberculosis. The ESAT-6 and CFP-10 proteins are secreted by M. tuberculosis and play important roles in pathogenesis. We hypothesized that these two proteins may affect the autophagy function of host macrophages during infection with M. tuberculosis, thereby shaping the immune reaction toward the pathogen. Interestingly, we found that rapamycin-induced autophagy of macrophages infected with M. tuberculosis H37Rv enhanced localization of mycobacteria with autophagosomes and lysosomes. Ectopic expression of the ESAT-6/CFP-10 fusion in macrophages dramatically inhibited autophagosome formation, and M. tuberculosis survival inside infected macrophages was significantly affected as well. Further, M. tuberculosis viability was increased by the fusion protein. Expression levels of autophagy-related genes (ATG), especially atg8, also decreased (p<0.05). These results suggested that ESAT-6 and CFP-10 proteins play significant roles in autophagy formation in M. tuberculosis infection and that autophagosome formation is regulated through the expression of ATG.
自噬在宿主固有和适应性免疫反应中发挥特定作用，可应对多种胞内病原体，包括结核分枝杆菌。ESAT-6 和 CFP-10 蛋白由结核分枝杆菌分泌，在发病机制中发挥重要作用。我们假设这两种蛋白可能会影响宿主巨噬细胞在感染结核分枝杆菌时的自噬功能，从而影响对病原体的免疫反应。有趣的是，我们发现，结核分枝杆菌 H37Rv 感染的巨噬细胞中雷帕霉素诱导的自噬会增强与自噬体和溶酶体结合的分枝杆菌定位。巨噬细胞中 ESAT-6/CFP-10 融合蛋白的异位表达会显著抑制自噬体的形成，同时也会显著影响感染巨噬细胞内结核分枝杆菌的存活。此外，融合蛋白还会增加结核分枝杆菌的活力。自噬相关基因（ATG）的表达水平，特别是 atg8，也会下降（p<0.05）。这些结果表明，ESAT-6 和 CFP-10 蛋白在结核分枝杆菌感染中的自噬形成中发挥重要作用，并且自噬体的形成是通过 ATG 的表达来调节的。
