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DNA Damage Primes t...
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Härtlova, AnettaUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Umeå Centre for Microbial Research (UCMR)
(author)
DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity.
- Article/chapterEnglish2015
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LIBRIS-ID:oai:gup.ub.gu.se/214495
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https://gup.ub.gu.se/publication/214495URI
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https://doi.org/10.1016/j.immuni.2015.01.012DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-101396URI
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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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Erttmann, Saskia F.Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR)(Swepub:umu)saer0053
(author)
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Raffi, Faizal AmUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
(author)
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Schmalz, Anja M.Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)(Swepub:umu)ansc0060
(author)
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Resch, UlrikeUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
(author)
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Anugula, SharathUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för molekylärbiologi (Medicinska fakulteten)
(author)
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Lienenklaus, Stefan
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Nilsson, Lisa M,1976Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center(Swepub:gu)xnilis
(author)
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Kröger, Andrea
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Nilsson, Jonas A,1971Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center(Swepub:gu)xnijon
(author)
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Ek, Torben
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Weiss, Siegfried
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Gekara, Nelson O.Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS)(Swepub:umu)fepe0003
(author)
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Umeå universitetMolekylär Infektionsmedicin, Sverige (MIMS)
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In:Immunity: Elsevier BV42:2, s. 332-431097-41801074-7613
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Härtlova, Anetta
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Raffi, Faizal Am
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Schmalz, Anja M.
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Resch, Ulrike
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Anugula, Sharath
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