Mycobacterium tuberculosis RKIP (Rv2140c) dephosphorylates ERK/NF-kappa B upstream signaling molecules to subvert macrophage innate immune response

文献类型： 外文期刊

第一作者： Abo-Kadoum, M. A.

作者： Abo-Kadoum, M. A.;Assad, Mohammed;Uae, Moure;Nzaou, Stech A. E.;Gong, Zhen;Teweldebrhan, Samson;Ai Xuefeng;Xie, Jianping;Abo-Kadoum, M. A.;Eltoukhy, Adel;Eltoukhy, Adel;Assad, Mohammed;Moaaz, Asmaa;Chen, Yu

作者机构：

关键词： Mycobacterium tuberculosis Rv2140c; RKIP; ERK; NF-kappa B; Phosphorylation; Apoptosis

期刊名称：INFECTION GENETICS AND EVOLUTION （ 影响因子：3.342； 五年影响因子：3.188 ）

ISSN： 1567-1348

年卷期： 2021 年 94 卷

页码：

收录情况： SCI

摘要： Mycobacterium tuberculosis (Mtb) survival and virulence largely reside on its ability to manipulate the host immune response. We have previously shown that M. tuberculosis Raf kinase inhibitor protein (RKIP) Rv2140c regulates diverse phosphorylation events in M. srnegmatis. However, its role during infection is unknown. In this report, we show that Rv2140c can mimic the mammalian RKIP function. Rv2140c inhibit the activation of extracellular signal-regulated kinase (ERK) and nuclear factor kappa B (NF-kappa B) via decreasing the phosphorylation capacity of upstream mediators MEK1, ERK1/2, and IKK alpha/beta thus leading to a reduction in pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha. This effect can be reversed by RKIP inhibitor locostatin. Furthermore Rv2140c mediates apoptosis associated with activation of caspases cascades. This modulation enhances the intracellular survival of M. srnegmatis within macrophage. We propose that Rv2140c is a multifunctional virulence factor and a promising novel anti-Tuberculosis drug target.

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