DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity - PubMed (original) (raw)

. 2015 Feb 17;42(2):332-343.

doi: 10.1016/j.immuni.2015.01.012.

Saskia F Erttmann 1, Faizal Am Raffi 1, Anja M Schmalz 1, Ulrike Resch 1, Sharath Anugula 1, Stefan Lienenklaus 2, Lisa M Nilsson 3, Andrea Kröger 2, Jonas A Nilsson 3, Torben Ek 4, Siegfried Weiss 2, Nelson O Gekara 5

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DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity

Anetta Härtlova et al. Immunity. 2015.

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Abstract

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

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