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 |
| PROVIDER: | wos |
| PUBMED: | 24777530 |
| PMCID: | PMC4309842 |
| Notes: | Article -- Source: Wos |
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