Innate Immune Response to Cytoplasmic DNA: Mechanisms and Diseases.

IF 26.9 1区医学 Q1 IMMUNOLOGY

Annual review of immunology Pub Date : 2019-12-04 DOI:10.1146/annurev-immunol-070119-115052

Ming-Ming Hu, H. Shu

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引用次数: 72

Abstract

DNA has been known to be a potent immune stimulus for more than half a century. However, the underlying molecular mechanisms of DNA-triggered immune response have remained elusive until recent years. Cyclic GMP-AMP synthase (cGAS) is a major cytoplasmic DNA senor in various types of cells that detect either invaded foreign DNA or aberrantly located self-DNA. Upon sensing of DNA, cGAS catalyzes the formation of cyclic GMP-AMP (cGAMP), which in turn activates the ER-localized adaptor protein MITA (also named STING) to elicit the innate immune response. The cGAS-MITA axis not only plays a central role in host defense against pathogen-derived DNA but also acts as a cellular stress response pathway by sensing aberrantly located self-DNA, which is linked to the pathogenesis of various human diseases. In this review, we summarize the spatial and temporal mechanisms of host defense to cytoplasmic DNA mediated by the cGAS-MITA axis and discuss the association of malfunctions of this axis with autoimmune and other diseases. Expected final online publication date for the Annual Review of Immunology, Volume 38 is April 26, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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细胞质DNA的先天免疫反应：机制和疾病。

半个多世纪以来，DNA一直被认为是一种强大的免疫刺激物。然而，直到最近几年，DNA引发免疫反应的潜在分子机制仍然难以捉摸。环状GMP-AMP合成酶（cGAS）是各种类型细胞中的主要细胞质DNA传感器，可检测入侵的外源DNA或定位异常的自身DNA。在感知DNA时，cGAS催化环状GMP-AMP（cGAMP）的形成，进而激活ER定位的衔接蛋白MITA（也称为STING）以引发先天免疫反应。cGAS-MITA轴不仅在宿主防御病原体来源的DNA中发挥核心作用，而且通过感应异常定位的自身DNA作为细胞应激反应途径，这与各种人类疾病的发病机制有关。在这篇综述中，我们总结了由cGAS-MITA轴介导的宿主对细胞质DNA防御的空间和时间机制，并讨论了该轴的功能障碍与自身免疫和其他疾病的关系。《免疫学年度评论》第38卷预计最终在线出版日期为2020年4月26日。请参阅http://www.annualreviews.org/page/journal/pubdates用于修订估算。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annual review of immunology 医学-免疫学

CiteScore

57.20

自引率

0.70%

发文量

期刊介绍： The Annual Review of Immunology, in publication since 1983, focuses on basic immune mechanisms and molecular basis of immune diseases in humans. Topics include innate and adaptive immunity; immune cell development and differentiation; immune control of pathogens (viruses, bacteria, parasites) and cancer; and human immunodeficiency and autoimmune diseases. The current volume of this journal has been converted from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.