Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1ß production.
Nat Immunol
; 15(6): 538-45, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24777530
ABSTRACT
Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1ß (IL-1ß) 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-1ß. Primary cells conditionally deficient in Rad50 or lacking CARD9 consequently exhibited defective DNA-induced production of IL-1ß, 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vaccinia virus
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DNA Viral
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Enzimas Reparadoras do DNA
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Proteínas de Ligação a DNA
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Interleucina-1beta
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Proteínas Adaptadoras de Sinalização CARD
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article