Wang Qiang, Liu Xing, Zhou Qin, Wang Chen
a 1 Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, State Key Laboratory of Cell Biology, Innovation Center for Cell Signaling Network, Chinese Academy of Sciences , Shanghai 200031, China
b 2 Chongqing Medical University, The College of Laboratory Medicine , 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, China
Expert Opin Ther Targets. 2015;19(10):1397-409. doi: 10.1517/14728222.2015.1067303. Epub 2015 Jul 28.
Detection of pathogen-derived nucleic acids is a general and effective strategy used by the host to perceive the presence of invading microorganisms and initiate an innate immune response. However, inappropriate detection of aberrant self nucleic acids is implicated in the development of autoimmune diseases. Recently, ER-resident stimulator of interferon genes (STING) has been uncovered as a key component in the innate immune response to cytosolic nucleic acids and a direct sensor for bacterial cyclic dinucleotides. The elucidation of STING-mediated signaling will provide insight into host-microbial interactions and contribute to the development of novel strategies for anti-infection therapies.
This review summarizes the cellular and molecular processes of host sensing and responding to microbial or endogenous aberrant DNA species, highlighting the essential function of STING and the corresponding regulatory mechanisms. The authors also attempt to delineate the role for the DNA-sensing signaling during the onset and progression of autoimmune diseases and suggest improvements in the immunogenicity of DNA vaccines.
It is essential to elucidate how the STING-dependent signaling mediates the DNA vaccines action as well as the pathogenesis of autoimmune diseases. The relevant knowledge will greatly benefit the treatment of infectious diseases and identify potential targets for effective drug design.
检测病原体衍生的核酸是宿主感知入侵微生物存在并启动固有免疫反应的一种常用有效策略。然而，对异常自身核酸的不适当检测与自身免疫性疾病的发生有关。最近，内质网驻留的干扰素基因刺激物（STING）已被发现是对胞质核酸固有免疫反应的关键组成部分以及细菌环二核苷酸的直接传感器。对STING介导信号传导的阐明将为宿主-微生物相互作用提供见解，并有助于开发新的抗感染治疗策略。
本综述总结了宿主感知和响应微生物或内源性异常DNA种类的细胞和分子过程，强调了STING的基本功能及相应的调节机制。作者还试图阐明DNA传感信号在自身免疫性疾病发生和发展过程中的作用，并提出改进DNA疫苗免疫原性的建议。
阐明STING依赖性信号传导如何介导DNA疫苗作用以及自身免疫性疾病的发病机制至关重要。相关知识将极大地有益于传染病的治疗，并为有效药物设计确定潜在靶点。
