Mycobacterium tuberculosis Rv1987 protein induces M2 polarization of macrophages through activating the PI3K/Akt1/mTOR signaling pathway,Immunology and Cell Biology

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Mycobacterium tuberculosis Rv1987 protein induces M2 polarization of macrophages through activating the PI3K/Akt1/mTOR signaling pathway
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2021-01-19 , DOI: 10.1111/imcb.12436
Shanshan Sha ₁ , Yang Shi ₁ , Yawei Tang ₂ , Liqiu Jia ₁ , Xiuyan Han ₁ , Yuxin Liu ₁ , Xia Li ₂ , Yufang Ma _{1,

3}

Affiliation

Mycobacterium tuberculosis (Mtb) can subvert host immune responses and survive in macrophages. Specific Mtb antigens play a critical role in this process. Rv1987, a secretory protein encoded by the gene rv1987 in the region of difference-2 (RD2) of the Mtb genome, is specifically expressed in pathogenic mycobacteria. Our previous work proved that Rv1987 induced a Th2 response in mice and enhanced mycobacterial survival in mouse lungs, but its effect on macrophages, the most important effector immune cell involved in killing Mtb, remains unclear. In this study, we used an M. smegmatis strain overexpressing Rv1987 protein to infect alveolar macrophages and the macrophage cell line RAW264.7 and analyzed the effect of Rv1987 protein on macrophage polarization. Rv1987 induced M2 polarization in macrophages both in vivo and in vitro. The bactericidal ability of these M2 polarized macrophages decreased remarkably, which resulted in the increased survival of bacteria in macrophages. Proteomics, RT-qPCR and western blotting results revealed that the PI3K/Akt1/mTOR signaling pathway was activated in Rv1987-induced M2 macrophages. Meanwhile, the SHIP molecule, a negative regulator of the PI3K/Akt1/mTOR signaling pathway, was significantly downregulated. These results suggest that Rv1987 plays an important role in modulating the host immune response and could be established as a potential drug target.

中文翻译：

结核分枝杆菌 Rv1987 蛋白通过激活 PI3K/Akt1/mTOR 信号通路诱导巨噬细胞 M2 极化

结核分枝杆菌(Mtb) 可以颠覆宿主免疫反应并在巨噬细胞中存活。特定的 Mtb 抗原在此过程中起着关键作用。Rv1987 是由Mtb 基因组差异 2 (RD2) 区域中的基因rv1987编码的分泌蛋白，在致病性分枝杆菌中特异性表达。我们之前的工作证明 Rv1987 在小鼠中诱导 Th2 反应并增强小鼠肺中分枝杆菌的存活率，但其对巨噬细胞的影响尚不清楚，巨噬细胞是参与杀死 Mtb 的最重要的效应免疫细胞。在这项研究中，我们使用了耻垢分枝杆菌菌株过表达 Rv1987 蛋白感染肺泡巨噬细胞和巨噬细胞系 RAW264.7，并分析了 Rv1987 蛋白对巨噬细胞极化的影响。Rv1987在体内和体外诱导巨噬细胞 M2 极化. 这些M2极化巨噬细胞的杀菌能力显着下降，导致巨噬细胞中细菌的存活率增加。蛋白质组学、RT-qPCR 和蛋白质印迹结果显示 PI3K/Akt1/mTOR 信号通路在 Rv1987 诱导的 M2 巨噬细胞中被激活。同时，作为 PI3K/Akt1/mTOR 信号通路负调节因子的 SHIP 分子被显着下调。这些结果表明 Rv1987 在调节宿主免疫反应中起着重要作用，可以作为潜在的药物靶点。

更新日期：2021-01-19

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