抗Mtb免疫信号通路环鸟苷酸-腺苷酸合成酶-干扰素基因刺激蛋白的研究进展

Research advance in cGAS-STING pathway： a pathway with anti-tuberculosis function of immune system

Mtb作为一种胞内寄生菌，细胞内如何识别其产物并启动固有免疫反应对Mtb的控制具有重要意义。干扰素基因刺激蛋白（stimulatorofinterferongenes，STING）是天然免疫反应信号通路中重要的衔接分子，Mtb感染过程中STING-TANK结合激酶1（TANK—bindingkinase1，TBK-1）一干扰素调节因子3（interferonregula—toryfactor3，IRF-3）信号通路在介导I型干扰素表达及诱导吞噬细胞自噬过程中发挥重要作用。最近的研究表明，环鸟苷酸一腺苷酸合成酶（cyclicGMP-AMPsynthase，cGAS）参与Mtb诱导的天然免疫反应，Mtb通过早期分泌抗原靶蛋白-6系统1（ESAT-6systeml，ESX-1）分泌系统介导的细菌DNA释放，从而激活cGAS-STING通路。笔者将对该信号通路在Mtb感染过程中发挥作用的机制及相关研究进行综述，以期增强我们对结核病的病理过程和机体免疫机制的理解，为更好地开拓新的抗结核药物提供新的思路。

Mycobacterium tuberculosis （Mtb） is an intracellular bacterium, it is of great significance for Mtb control to know how to identify the intracellular product and trigger the innate immune response. Stimulator of in- terferon genes （STING） is an important signal adapter molecule in innate immune system. STING-TANK-binding kinase 1-interferon regulatory factor 3 （STINC-TBKI-IRF3） signaling pathways play an important role in the process of expression of type I interferon and autophagy induction in phagocytes infected by Mtb. Recent studies have shown that cyclic GMP-AMP synthase （cGAS） participates in the innate immune response induced by Mtb. Through secreting bacterial DNA release mediated by ESAT-6 system 1 （ESX 1） secretion system, Mtb activates eGAS-STING pathway. This article will summarize the mechanism and the related studies of this signaling pathway in the process of Mtb infection. It will help to enhance our understanding of pathological process of tuberculosis and the host immune mechanism, and provide some new idea for developing new anti tuberculosis drugs as well.