Titel
Type I Interferon Inhibits Interleukin-1 Production and Inflammasome Activation
Autor*in
Greta Guarda
University of Lausanne
Jürg Tschopp
University of Lausanne
Marion Braun
University of Lausanne
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Abstract
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-1 beta 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-1 alpha and pro-IL-1 beta. In vivo, poly(I:C)-induced type I IFN diminished IL-1 13 production in response to alum and Candida albicans, thus increasing susceptibility to this fungal pathogen. Importantly, monocytes from multiple sclerosis patients undergoing IFN-beta treatment produced substantially less IL-1 beta 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.
Stichwort
FAMILIAL MEDITERRANEAN FEVERMULTIPLE-SCLEROSISHOST-DEFENSERECOMBINANT INTERLEUKIN-1BACTERIAL-INFECTIONRECEPTOR ANTAGONISTCASPASE-1INNATEMICECRYSTALS
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Immunity
Band
34
Ausgabe
2
Seitenanfang
213
Seitenende
223
Erscheinungsdatum
01.01.2011
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