College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
State Key Laboratory of Veterinary Biotechnology, Division of Bacterial Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Microb Pathog. 2019 Jan;126:63-73. doi: 10.1016/j.micpath.2018.10.030. Epub 2018 Oct 23.
The capacity of Mycobacterium tuberculosis to survive and cause disease is strongly correlated with its ability to escape multiple defense strategies in hosts. In particular, M. tuberculosis has the remarkable capacity to survive within the hostile environment of macrophages. Here, we found that the PE17 (Rv1646) protein promoted intracellular survival of M. smegmatis in peritoneal macrophages from mice. Further experiments confirmed that the recombinant PE17 protein was localized in the cell wall of M. smegmatis. Results from the macrophage infection model showed that PE17 significantly downregulated pro-inflammatory cytokines (interleukin-6, interleukin-12, and tumer necrosis factor-α) secretion from macrophages induced by M. smegmatis and promoted macrophage necrosis. Furthermore, a C57BL/6 mouse infection model confirmed that PE17 significantly prolonged the survival of M. smegmatis in vivo and aggravated lesions in organs of infected mice. Moreover, persistent high levels of interferon-γ and interleukin-1β in infected mice indicated that the bacteria were not easily removed in vivo. Overall, our present results suggested that the PE17 may act as an important pathogenic factor in M. tuberculosis.
结核分枝杆菌的生存和致病能力与其在宿主中逃避多种防御策略的能力密切相关。特别是，结核分枝杆菌具有在巨噬细胞这种恶劣环境中生存的非凡能力。在这里，我们发现 PE17（Rv1646）蛋白可促进耻垢分枝杆菌在来自小鼠的腹腔巨噬细胞中的细胞内存活。进一步的实验证实，重组 PE17 蛋白定位于耻垢分枝杆菌的细胞壁上。巨噬细胞感染模型的结果表明，PE17 显著下调了耻垢分枝杆菌诱导的巨噬细胞中促炎细胞因子（白细胞介素-6、白细胞介素-12 和肿瘤坏死因子-α）的分泌，并促进了巨噬细胞坏死。此外，C57BL/6 小鼠感染模型证实，PE17 显著延长了耻垢分枝杆菌在体内的存活时间，并加重了感染小鼠器官的损伤。此外，感染小鼠中干扰素-γ和白细胞介素-1β的持续高水平表明，这些细菌在体内不易被清除。总体而言，我们目前的结果表明，PE17 可能是结核分枝杆菌中的一个重要致病因子。
