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DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity.
Härtlova, Anetta Erttmann, Saskia F Raffi, Faizal Am Schmalz, Anja M Resch, Ulrike Anugula, Sharath Lienenklaus, Stefan Nilsson, Lisa M Kröger, Andrea Nilsson, Jonas A
Härtlova, Anetta
Erttmann, Saskia F
Raffi, Faizal Am
Schmalz, Anja M
Resch, Ulrike
Anugula, Sharath
Lienenklaus, Stefan
Nilsson, Lisa M
Kröger, Andrea
Nilsson, Jonas A
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2015-02-17
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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.
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DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity. 2015, 42 (2):332-43 Immunity
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en
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1097-4180