Abstract：
Mycobacterium tuberculosis (M. tb) is a significant intracellular pathogen responsible for numerous infectious disease-related deaths worldwide. It uses ESX-1 T7SS to damage phagosomes and to enter the cytosol of host cells after phagocytosis. During infection, M. tb and host mitochondria release dsDNA, which activates the CGAS-STING1 pathway. This pathway leads to the production of type I interferons and proinflammatory cytokines and activates autophagy, which targets and degrades bacteria within autophagosomes. However, the role of type I IFNs in immunity against M. tb is controversial. While previous research has suggested a protective role, recent findings from cgas-sting1 knockout mouse studies have contradicted this. Additionally, a study using knockout mice and non-human primate models uncovered a new mechanism by which neutrophils recruited to lung infections form neutrophil extracellular traps. Activating plasmacytoid dendritic cells causes them to produce type I IFNs, which interfere with the function of interstitial macrophages and increase the likelihood of tuberculosis. Notably, M. tb uses its virulence proteins to disrupt the CGAS-STING1 signaling pathway leading to enhanced pathogenesis. Investigating the CGAS-STING1 pathway can help develop new ways to fight tuberculosis.
摘要：
结核分枝杆菌（M.tb）是一种重要的细胞内病原体，可导致全球许多与传染病相关的死亡。它使用ESX-1T7SS破坏吞噬体并在吞噬作用后进入宿主细胞的细胞质。在感染期间,结核分枝杆菌和宿主线粒体释放dsDNA，激活CGAS-STING1途径。该途径导致I型干扰素和促炎细胞因子的产生，并激活自噬，它靶向和降解自噬体内的细菌。然而,I型IFN在抗结核分枝杆菌免疫中的作用是有争议的。虽然以前的研究表明了保护作用，cgas-sting1基因敲除小鼠研究的最新发现与此相矛盾。此外,一项使用基因敲除小鼠和非人灵长类动物模型的研究发现了一种新的机制，通过该机制，被招募到肺部感染的中性粒细胞形成中性粒细胞胞外陷阱。激活浆细胞样树突状细胞导致它们产生I型IFN，干扰间质巨噬细胞的功能并增加结核病的可能性。值得注意的是,M.tb利用其毒力蛋白破坏CGAS-STING1信号通路，导致发病机制增强。研究CGAS-STING1途径可以帮助开发对抗结核病的新方法。
