DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity.
dc.contributor.author | Härtlova, Anetta | |
dc.contributor.author | Erttmann, Saskia F | |
dc.contributor.author | Raffi, Faizal Am | |
dc.contributor.author | Schmalz, Anja M | |
dc.contributor.author | Resch, Ulrike | |
dc.contributor.author | Anugula, Sharath | |
dc.contributor.author | Lienenklaus, Stefan | |
dc.contributor.author | Nilsson, Lisa M | |
dc.contributor.author | Kröger, Andrea | |
dc.contributor.author | Nilsson, Jonas A | |
dc.contributor.author | Ek, Torben | |
dc.contributor.author | Weiss, Siegfried | |
dc.contributor.author | Gekara, Nelson O | |
dc.date.accessioned | 2015-03-09T14:06:57Z | en |
dc.date.available | 2015-03-09T14:06:57Z | en |
dc.date.issued | 2015-02-17 | en |
dc.identifier.citation | 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 | en |
dc.identifier.issn | 1097-4180 | en |
dc.identifier.pmid | 25692705 | en |
dc.identifier.doi | 10.1016/j.immuni.2015.01.012 | en |
dc.identifier.uri | http://hdl.handle.net/10033/346334 | en |
dc.description.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. | |
dc.language.iso | en | en |
dc.title | DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity. | en |
dc.type | Article | en |
dc.contributor.department | Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. | en |
dc.identifier.journal | Immunity | en |
refterms.dateFOA | 2018-06-13T15:30:33Z | |
html.description.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. |