DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity.

2.50
Hdl Handle:
http://hdl.handle.net/10033/346334
Title:
DNA Damage Primes the Type I Interferon System via the Cytosolic DNA Sensor STING to Promote Anti-Microbial Innate Immunity.
Authors:
Härtlova, Anetta; Erttmann, Saskia F; Raffi, Faizal Am; Schmalz, Anja M; Resch, Ulrike; Anugula, Sharath; Lienenklaus, Stefan; Nilsson, Lisa M; Kröger, Andrea ( 0000-0002-3131-6580 ) ; Nilsson, Jonas A; Ek, Torben; Weiss, Siegfried; Gekara, Nelson O
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
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
Journal:
Immunity
Issue Date:
17-Feb-2015
URI:
http://hdl.handle.net/10033/346334
DOI:
10.1016/j.immuni.2015.01.012
PubMed ID:
25692705
Type:
Article
Language:
en
ISSN:
1097-4180
Appears in Collections:
publications of the research group immunity and infection (IMMI)

Full metadata record

DC FieldValue Language
dc.contributor.authorHärtlova, Anettaen
dc.contributor.authorErttmann, Saskia Fen
dc.contributor.authorRaffi, Faizal Amen
dc.contributor.authorSchmalz, Anja Men
dc.contributor.authorResch, Ulrikeen
dc.contributor.authorAnugula, Sharathen
dc.contributor.authorLienenklaus, Stefanen
dc.contributor.authorNilsson, Lisa Men
dc.contributor.authorKröger, Andreaen
dc.contributor.authorNilsson, Jonas Aen
dc.contributor.authorEk, Torbenen
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorGekara, Nelson Oen
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.en
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

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