Type I Interferon Inhibits Interleukin-1 Production and Inflammasome Activation

被引：928

作者：

Guarda, Greta ^{[1
]}

Braun, Marion ^{[2
]}

Staehli, Francesco ^{[1
]}

Tardivel, Aubry ^{[1
]}

Mattmann, Chantal ^{[1
]}

Foerster, Irmgard ^{[3
]}

Farlik, Matthias ^{[4
]}

Decker, Thomas ^{[4
]}

Du Pasquier, Renaud A. ^{[5
,6
]}

Romero, Pedro ^{[2
]}

Tschopp, Juerg ^{[1
]}

机构：

[1] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[2] Ludwig Inst Canc Res, CH-1011 Lausanne, Switzerland

[3] Univ Dusseldorf, Inst Umweltmed Forsch gGmbH, D-40225 Dusseldorf, Germany

[4] Univ Vienna, Max F Perutz Labs, Dept Genet Microbiol & Immunobiol, A-1030 Vienna, Austria

[5] Univ Lausanne Hosp, Serv Neurol, Dept Clin Neurosci, CH-1011 Lausanne, Switzerland

[6] Univ Lausanne Hosp, Serv Immunol, CH-1011 Lausanne, Switzerland

来源：

IMMUNITY | 2011年 / 34卷 / 02期

基金：

瑞士国家科学基金会;

关键词：

FAMILIAL MEDITERRANEAN FEVER; MULTIPLE-SCLEROSIS; HOST-DEFENSE; RECOMBINANT INTERLEUKIN-1; BACTERIAL-INFECTION; RECEPTOR ANTAGONIST; CASPASE-1; INNATE; MICE; CRYSTALS;

D O I：

10.1016/j.immuni.2011.02.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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.

引用

页码：213 / 223

页数：11

共 44 条

[1]

The NLRP3 Inflammasome Mediates In Vivo Innate Immunity to Influenza A Virus through Recognition of Viral RNA [J].