| First Author | Roth S | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 6 | Pages | 538-45 |
| PubMed ID | 24777530 | Mgi Jnum | J:259153 |
| Mgi Id | MGI:6142457 | Doi | 10.1038/ni.2888 |
| Citation | Roth S, et al. (2014) Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1beta production. Nat Immunol 15(6):538-45 |
| abstractText | Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1beta (IL-1beta) 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-kappaB and the generation of pro-IL-1beta. Primary cells conditionally deficient in Rad50 or lacking CARD9 consequently exhibited defective DNA-induced production of IL-1beta, 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. |
