IL-6 inhibits IFN-γ induced autophagy in Mycobacterium tuberculosis H37Rv infected macrophages
IL-6 inhibits IFN-γ induced autophagy in Mycobacterium tuberculosis H37Rv infected macrophages
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DOI：
10.1016/j.biocel.2012.02.021
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发表时间：
2012-06-01
影响因子：
4
通讯作者：
Majumdar, Sekhar
中科院分区：
文献类型：
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作者：
Dutta, Rajesh Kumar;Kathania, Mahesh;Majumdar, Sekhar
尽管IL-6干扰IFN-γ诱导的信号已经知道了相当长的时间，但IL-6产生在结核病中的重要性尚未完全阐明。为了知道IFN-γ诱导的细胞过程实际上被IL-6抵消，我们研究了IL-6对IFN-γ诱导的THP-1细胞中毒性结核分枝杆菌感染中的自噬形成的作用，因为它被很好地表征为IFN-γ诱导的自噬通过克服由杆菌施加的吞噬体成熟阻断而消除细胞内分枝杆菌。我们在此报道IL-6抑制IFN-γ和饥饿诱导的M.结核病H37 Rv感染的细胞。M.结核病H37 Rv感染导致THP-1细胞中IL-6的时间依赖性产生，并且抗IL-6抗体对这种内源性IL-6的中和显著增强了IFN-γ介导的细胞内细菌的杀伤。IL-6时间依赖性地降低Atg 12-Atg 5复合物，因此抑制自噬体生物合成而不是自噬溶酶体形成。IL-6还影响IFN-γ介导的mTOR、p-38和JNK途径的刺激。这些结果清楚地表明，毒性分枝杆菌策略性地上调IL-6的产生以对抗先天免疫。(C)2012爱思唯尔有限公司保留所有权利。
The significance of IL-6 production in tuberculosis is yet to be fully elucidated, although it is known for quite some time that IL-6 interferes with IFN-gamma induced signal. In order to know which cellular process induced by IFN-gamma is actually counteracted by IL-6, we studied the role of IL-6 on IFN-gamma induced autophagy formation in virulent Mycobacterium tuberculosis infection in THP-1 cells, since it is well characterized that induction of autophagy by IFN-gamma eliminates intracellular mycobacterium by overcoming the phagosome maturation block imposed by bacilli. We report here that IL-6 inhibits both IFN-gamma and starvation induced autophagy in M. tuberculosis H37Rv infected cells. M. tuberculosis H37Rv infection results in time dependent production of IL-6 in THP-1 cells and neutralization of this endogenous IL-6 by anti-IL-6 antibody significantly enhances the IFN-gamma mediated killing of the intracellular bacteria. IL-6 time dependently lowers Atg12-Atg5 complex and therefore inhibits autophagosome biogenesis rather than autophagolysosome formation. IL-6 also affects IFN-gamma mediated stimulation of mTOR, p-38 and JNK pathways. These results clearly indicate that virulent mycobacteria strategically upregulate IL-6 production to combat innate immunity. (C) 2012 Elsevier Ltd. All rights reserved.