生物
先天免疫系统
干扰素基因刺激剂
刺
共济失调毛细血管扩张
DNA损伤
Ⅰ型干扰素
干扰素
DNA
细胞生物学
信号转导
钻机-I
中性粒细胞胞外陷阱
启动(农业)
免疫学
免疫系统
效应器
内部收益率3
遗传学
航空航天工程
工程类
发芽
植物
作者
Anetta Härtlová,Saskia F. Erttmann,Faizal A.M. Raffi,Anja M. Schmalz,Ulrike Resch,Sharath Anugula,Stefan Lienenklaus,Lisa M. Nilsson,Andrea Kröger,Jonas A. Nilsson,Torben Ek,Nelson O. Gekara
出处
期刊:Immunity
[Elsevier]
日期:2015-02-01
卷期号:42 (2): 332-343
被引量:546
标识
DOI:10.1016/j.immuni.2015.01.012
摘要
Dysfunction in Ataxia-telangiectasia mutated (ATM), a central component of the DNA repair machinery, results in Ataxia Telangiectasia (AT), a cancer-prone disease with a variety of inflammatory manifestations. By analyzing AT patient samples and Atm(-/-) mice, we found that unrepaired DNA lesions induce type I interferons (IFNs), resulting in enhanced anti-viral and anti-bacterial responses in Atm(-/-) mice. Priming of the type I interferon system by DNA damage involved release of DNA into the cytoplasm where it activated the cytosolic DNA sensing STING-mediated pathway, which in turn enhanced responses to innate stimuli by activating the expression of Toll-like receptors, RIG-I-like receptors, cytoplasmic DNA sensors, and their downstream signaling partners. This study provides a potential explanation for the inflammatory phenotype of AT patients and establishes damaged DNA as a cell intrinsic danger signal that primes the innate immune system for a rapid and amplified response to microbial and environmental threats.
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