摘要
细胞胞质中存在的游离DNA一直被宿主的固有免疫系统当做潜在的危险信号,但免疫系统识别和清除这些危险信号的机制还不明确.近几年有研究发现,DNA感受器(DNA sensor)是宿主感受DNA和免疫防御的桥梁,目前已经有超过10种DNA感受器被发现,而干扰素刺激基因(stimulator of interferon genes,STING,也称为TMEM173、MPYS、MITA和ERIS)作为一种DNA感受通路下游关键的接头分子,在感受胞质DNA和免疫防御方面起着重要的信号传递作用,胞质中的DNA可通过DNA感受器激活STING,再激活Ⅰ型干扰素和其他细胞因子,进而启动机体的免疫反应.近些年,胞质中游离DNA如何激活STING,进而如何在体内启动免疫反应以产生抗病毒或抗菌作用的机制研究取得了显著进展.最近,在哺乳动物细胞中发现了一种新型的核酸转移酶cGAS(cyclic GMP-AMPsynthase),它能识别DNA并能产生一种内源性的环化二核苷酸cGAMP(cyclic GMP-AMP)激活STING.本文将最近关于cGAS的发现、胞质DNA通过cGAS激活STING及STING活化后激活机体免疫反应的机制进行了综述.
The dangerous signature came from unintegrated DNA or episome in cytoplasm could be detected by innate immunity, but how it works is unclear. Recently, more than 10 DNA sensors have been found to connect with the DNA sensing and immune defense. The cytosolic DNA induces the type I interferon and other cytokines depended on the stimulator of interferon genes, namely STING （also known as ELLIS, MITA, MPYS, and TMEM173）, which functions as a key adaptor protein in the DNA sensing pathways. Surprisingly, some investigators identified a novel nucleotidyl transferase, cGAS, which produces an endogenous second-messenger cGAMP to activate STING in the cytoplasm of mammalian cells. However, how DNA activates STING to induce protective immune responses against virus, protozoa and bacteria need to be explored further. In this review, we discuss the recent research progress regarding the DNA sensing by cGAS and the mechanisms involved in activation of STING and subsequently immune responses.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2014年第9期830-838,共9页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金资助项目(81072213,81271698)
国家临床重点专科建设项目(2011)
江苏省临床医学科技专项(BL2012017)
南京市医学重点实验室建设项目(2012)
南京市医学科技发展项目(YKK09124)~~
