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Roth, S.* ; Rottach, A.* ; Lotz-Havla, A.S.* ; Laux, V.* ; Muschaweckh, A. ; Gersting, S.W.* ; Muntau, A.C.* ; Hopfner, K.P.* ; Jin, L.* ; Vanness, K.* ; Petrini, J.H.* ; Drexler, I. ; Leonhardt, H.* ; Ruland, J.*

Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production.

Nat. Immunol. 15, 538-545 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1β (IL-1β) as an antiviral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune system adaptor CARD9. Transfection of dendritic cells with dsDNA or infection of dendritic cells with a DNA virus induced the formation of dsDNA-Rad50-CARD9 signaling complexes for activation of the transcription factor NF-κB and the generation of pro-IL-1β. Primary cells conditionally deficient in Rad50 or lacking CARD9 consequently exhibited defective DNA-induced production of IL-1β, and Card9(-/-) mice had impaired inflammatory responses after infection with a DNA virus in vivo. Our results define a cytosolic DNA-recognition pathway for inflammation and a physical and functional connection between a conserved DNA-damage sensor and the innate immune response to pathogens.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Vaccinia Virus Ankara; Adapter Protein Card9; Cyclic Gmp-amp; Innate Immunity; I Interferon; Aim2 Inflammasome; Damage Response; Dendritic Cells; Rig-i; Receptors
Language english
Publication Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Journal Nature Immunology
Quellenangaben Volume: 15, Issue: 6, Pages: 538-545 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-502700-002
PubMed ID 24777530
DOI 10.1038/ni.2888
WOS ID WOS:000336419300010
Erfassungsdatum 2014-05-01
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