线粒体DNA与cGAS-STING通路在抗菌抗病毒免疫中的研究进展

Research progress of mitochondrial DNA and cGAS-STING pathway in antibacterial and antiviral immunity

线粒体除了产生ATP为真核生物提供能量外,还参与抗细菌病毒感染过程。线粒体DNA(mtDNA)在各种细菌病毒感染的刺激下均能引起损伤。细菌病毒感染能够引起线粒体转录因子A蛋白丢失,或通过Ⅶ型分泌系统、线粒体抗病毒信号蛋白和线粒体膜通透性转换孔介导等不同方式将mtDNA释放到细胞质中从而激活环状GMP-AMP合成酶(cGAS)、DEAD盒解旋酶41、NOD样受体热蛋白结构域相关蛋白3和Toll样受体-9等DNA受体多种途径。其中cGAS可通过催化第二信使环鸟苷酸-腺苷酸后激活干扰素基因刺激因子(STING)依赖的信号通路并诱导Ⅰ型干扰素、肿瘤坏死因子-α、白细胞介素-6等炎症因子的表达,并在抵抗病原微生物感染中发挥重要作用。本文综述了mtDNA-cGAS-STING通路在抗菌抗病毒免疫中的研究进展,为开发特异性杀死细菌病毒的新型抗菌药物奠定基础,同时也有助于更好地理解线粒体与宿主免疫系统的相互作用。

Mitochondria contribute to the process of resistance against bacterial and viral infections in addition to generating ATP to provide energy to eukaryotes.Damage to mitochondrial DNA(mtDNA)can occur when specific stimuli associated with bacterial or viral infections are present.A multitude of processes,such as the mitochondrial antiviral signaling protein,mitochondrial permeability transition pore-mediated,typeⅦsecretion system,and loss of mitochondrial transcription factor A proteins,can lead to the release of mtDNA into the cytoplasm,and can consequently activate many DNA receptor pathways,such as GMP-AMP synthase(cGAS),DEAD-box helicase 41,NOD-like receptor protein 3,and Toll-like receptor 9.Among them,cGAS plays a crucial role in preventing pathogenic microbial infections by activating the STING-dependent signaling cascade of interferon-stimulated genes and inducing the expression of inflammatory proteins like interferon type-I,tumor necrosis factor-alpha,interleukin-6,after catalyzing the second messenger cyclic GMP-AMP.We review the progress made in studying the mtDNA-cGAS-STING pathway in antiviral and antibacterial immunity in this paper.This pathway not only helps to better understand the interactions between mitochondria and the host immune system,but also paves the way for the development of novel antimicrobial drugs that target and kill bacterial viruses.