Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1 beta production Journal Article

Authors: 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. J.; Drexler, I.; Leonhardt, H.; Ruland, J.
Article Title: Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1 beta production
Abstract: Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1 beta (IL-1 beta) 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-kappa B and the generation of pro-IL-1 beta. Primary cells conditionally deficient in Rad50 or lacking CARD9 consequently exhibited defective DNA-induced production of IL-1 beta, 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.
Keywords: immunity; cells; receptors; damage response; dendritic; i interferon; innate; rig-i; vaccinia virus ankara; adapter protein card9; cyclic gmp-amp; aim2 inflammasome
Journal Title: Nature Immunology
Volume: 15
Issue: 6
ISSN: 1529-2908
Publisher: Nature Publishing Group  
Date Published: 2014-06-01
Start Page: 538
End Page: 545
Language: English
ACCESSION: WOS:000336419300010
DOI: 10.1038/ni.2888
PUBMED: 24777530
PMCID: PMC4309842
Notes: Article -- Source: Wos
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MSK Authors
  1. John Petrini
    87 Petrini