University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France.
Sci Rep. 2016 Jul 7;6:29297. doi: 10.1038/srep29297.
Mycobacterium tuberculosis is a successful intracellular pathogen. Numerous host innate immune responses signaling pathways are induced upon mycobacterium invasion, however their impact on M. tuberculosis replication is not fully understood. Here we reinvestigate the role of STAT3 specifically inside human macrophages shortly after M. tuberculosis uptake. We first show that STAT3 activation is mediated by IL-10 and occurs in M. tuberculosis infected cells as well as in bystander non-colonized cells. STAT3 activation results in the inhibition of IL-6, TNF-α, IFN-γ and MIP-1β. We further demonstrate that STAT3 represses iNOS expression and NO synthesis. Accordingly, the inhibition of STAT3 is detrimental for M. tuberculosis intracellular replication. Our study thus points out STAT3 as a key host factor for M. tuberculosis intracellular establishment in the early stages of macrophage infection.
结核分枝杆菌是一种成功的细胞内病原体。在分枝杆菌入侵后，宿主先天免疫反应信号通路被大量诱导，但其对结核分枝杆菌复制的影响尚不完全清楚。在这里，我们在分枝杆菌摄取后不久，重新研究了 STAT3 在人巨噬细胞内的特定作用。我们首先表明，STAT3 的激活是由 IL-10 介导的，并且发生在分枝杆菌感染的细胞以及未被感染的旁观者细胞中。STAT3 的激活导致 IL-6、TNF-α、IFN-γ 和 MIP-1β 的抑制。我们进一步证明 STAT3 抑制 iNOS 表达和 NO 合成。因此，STAT3 的抑制对结核分枝杆菌的细胞内复制是有害的。因此，我们的研究指出 STAT3 是宿主细胞内感染早期巨噬细胞中结核分枝杆菌建立的关键宿主因子。
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