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dc.contributor.authorHärtlova, Anetta
dc.contributor.authorErttmann, Saskia F
dc.contributor.authorRaffi, Faizal Am
dc.contributor.authorSchmalz, Anja M
dc.contributor.authorResch, Ulrike
dc.contributor.authorAnugula, Sharath
dc.contributor.authorLienenklaus, Stefan
dc.contributor.authorNilsson, Lisa M
dc.contributor.authorKröger, Andrea
dc.contributor.authorNilsson, Jonas A
dc.contributor.authorEk, Torben
dc.contributor.authorWeiss, Siegfried
dc.contributor.authorGekara, Nelson O
dc.date.accessioned2015-03-09T14:06:57Zen
dc.date.available2015-03-09T14:06:57Zen
dc.date.issued2015-02-17en
dc.identifier.citationDNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity. 2015, 42 (2):332-43 Immunityen
dc.identifier.issn1097-4180en
dc.identifier.pmid25692705en
dc.identifier.doi10.1016/j.immuni.2015.01.012en
dc.identifier.urihttp://hdl.handle.net/10033/346334en
dc.description.abstractDysfunction 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.isoenen
dc.titleDNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalImmunityen
refterms.dateFOA2018-06-13T15:30:33Z
html.description.abstractDysfunction 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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