Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Protein Cell. 2016 Nov;7(11):777-791. doi: 10.1007/s13238-016-0320-3. Epub 2016 Sep 30.
The host takes use of pattern recognition receptors (PRRs) to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.
宿主利用模式识别受体(PRRs)来防御病原体入侵或细胞损伤。在宿主 PRRs 检测到的微生物相关分子模式中,细菌或病毒衍生的核酸受到严密监管,为宿主防御提供了一个基本机制。DNA 传感器被认为可以检测到致病性 DNA,从而诱导 NFκB 或 TBK1-IRF3 通路的激活。cGAS 在先天免疫细胞中广泛表达,是几种细胞类型中入侵 DNA 的关键传感器。cGAS 与 DNA 结合,随后发生构象变化,使三磷酸腺苷和三磷酸鸟苷合成环鸟苷酸单磷酸-腺苷酸单磷酸(cGAMP)。cGAMP 是 STING 的强激活剂,可激活 IRF3 并随后产生 I 型干扰素。本文描述了针对致病性 DNA 的先天免疫反应中 DNA 传感器特别是 cGAS 的最新进展。