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Roth et al. (2014); Nature Immunology (Leonhardt lab)


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

Susanne Roth, Andrea Rottach, Amelie S Lotz-Havla, Verana Laux, Andreas Muschaweckh, Soren W Gersting, Ania C Muntau, Karl-Peter Hopfner, Lei Jin, Katelynd Vanness, John H J Petrini, Ingo Drexler, Heinrich Leonhardt and Jürgen Ruland

Nature Immunology (2014) doi: 10.1038/ni.2888

teaser roth et al 130x130Double-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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