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Type I Interferon Inhibits Interleukin-1 Production and Inflammasome Activation

2011; Cell Press; Volume: 34; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2011.02.006

1097-4180

Greta Guarda, Marion Braun, Francesco Staehli, Aubry Tardivel, Chantal Mattmann, Irmgard Förster, Matthias Farlik, Thomas Decker, Renaud Du Pasquier, Pedro Romero, Jürg Tschopp,

Cancer-related molecular mechanisms research

Type I interferon (IFN) is a common therapy for autoimmune and inflammatory disorders, yet the mechanisms of action are largely unknown. Here we showed that type I IFN inhibited interleukin-1 (IL-1) production through two distinct mechanisms. Type I IFN signaling, via the STAT1 transcription factor, repressed the activity of the NLRP1 and NLRP3 inflammasomes, thereby suppressing caspase-1-dependent IL-1β maturation. In addition, type I IFN induced IL-10 in a STAT1-dependent manner; autocrine IL-10 then signaled via STAT3 to reduce the abundance of pro-IL-1α and pro-IL-1β. In vivo, poly(I:C)-induced type I IFN diminished IL-1β production in response to alum and Candida albicans, thus increasing susceptibility to this fungal pathogen. Importantly, monocytes from multiple sclerosis patients undergoing IFN-β treatment produced substantially less IL-1β than monocytes derived from healthy donors. Our findings may thus explain the effectiveness of type I IFN in the treatment of inflammatory diseases but also the observed “weakening” of the immune system after viral infection.