IL-17A Promotes Intracellular Growth of Mycobacterium by Inhibiting Apoptosis of Infected Macrophages.
IL-17A Promotes Intracellular Growth of Mycobacterium by Inhibiting Apoptosis of Infected Macrophages.
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IL-17A通过抑制感染巨噬细胞的凋亡来促进分枝杆菌的细胞内生长。
DOI：
10.3389/fimmu.2015.00498
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发表时间：
2015
影响因子：
7.3
通讯作者：
Castro AG
中科院分区：
文献类型：
--
作者：
Cruz A;Ludovico P;Torrado E;Gama JB;Sousa J;Gaifem J;Appelberg R;Rodrigues F;Cooper AM;Pedrosa J;Saraiva M;Castro AG
受感染的巨噬细胞的命运是对分枝杆菌免疫的关键方面。通过剥夺病原体的细胞内生态位，感染的巨噬细胞的凋亡死亡已被证明是控制细菌生长的重要机制。在这里，我们表明，IL-17抑制细胞凋亡的牛分枝杆菌卡介苗或结核分枝杆菌感染的巨噬细胞，从而阻碍他们的能力，控制细菌生长。从机制上讲，我们表明IL-17抑制p53，并通过增加Bcl-2和减少Bax表达，减少线粒体释放细胞色素c，抑制caspase-3激活来影响内在凋亡途径。在感染的巨噬细胞中，在阻断p53核转位后观察到IL-17的相同作用。这些结果揭示了IL-17/p53轴在分枝杆菌诱导的细胞凋亡的调节中以前未被认识到的作用，并且在感染细胞的细胞凋亡是重要的宿主防御机制的广谱疾病中可能具有重要意义。
The fate of infected macrophages is a critical aspect of immunity to mycobacteria. By depriving the pathogen of its intracellular niche, apoptotic death of the infected macrophage has been shown to be an important mechanism to control bacterial growth. Here, we show that IL-17 inhibits apoptosis of Mycobacterium bovis BCG- or Mycobacterium tuberculosis-infected macrophages thus hampering their ability to control bacterial growth. Mechanistically, we show that IL-17 inhibits p53, and impacts on the intrinsic apoptotic pathway, by increasing the Bcl2 and decreasing Bax expression, decreasing cytochrome c release from the mitochondria, and inhibiting caspase-3 activation. The same effect of IL-17 was observed in infected macrophages upon blockade of p53 nuclear translocation. These results reveal a previously unappreciated role for the IL-17/p53 axis in the regulation of mycobacteria-induced apoptosis and can have important implications in a broad spectrum of diseases where apoptosis of the infected cell is an important host defense mechanism.