IL-37 inhibits inflammasome activation and disease severity in murine aspergillosis.
Since IL-37 transgenic mice possesses broad anti-inflammatory properties, we assessed whether recombinant IL-37 affects inflammation in a murine model of invasive pulmonary aspergillosis. Recombinant human IL-37 was injected intraperitoneally into mice prior to infection and the effects on lung inflammation and inflammasome activation were evaluated. IL-37 markedly reduced NLRP3-dependent neutrophil recruitment and steady state mRNA levels of IL-1β production and mitigated lung inflammation and damage in a relevant clinical model, namely aspergillosis in mice with cystic fibrosis. The anti-inflammatory activity of IL-37 requires the IL-1 family decoy receptor TIR-8/SIGIRR. Thus, by preventing activation of the NLRP3 inflammasome and reducing IL-1β secretion, IL-37 functions as a broad spectrum inhibitor of the innate response to infection-mediated inflammation, and could be considered to be therapeutic in reducing the pulmonary damage due to non-resolving Aspergillus infection and disease.
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Silvia
S
Moretti
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Silvia
S
Bozza
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Vasilis
V
Oikonomou
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Giorgia
G
Renga
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy; Istituto Superiore di Sanità, Roma, Italy.
Andrea
A
Casagrande
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Rossana G
RG
Iannitti
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Matteo
M
Puccetti
Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Cecilia
C
Garlanda
Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
Soohyun
S
Kim
Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.
Suzhao
S
Li
Department of Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Frank L
FL
van de Veerdonk
Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America; Department of Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
Charles A
CA
Dinarello
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Luigina
L
Romani
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D055732:Pulmonary Aspergillosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology
D002352:Carrier Proteins; D058847:Inflammasomes; D007375:Interleukin-1; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017472:Receptors, Interleukin-1; C587672:IL1B protein, mouse; C492716:Nlrp3 protein, mouse; C484529:SIGIRR protein, mouse