IL-37 Inhibits Inflammasome Activation and Disease Severity in Murine Aspergillosis |
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| Authors: | Silvia Moretti Silvia Bozza Vasilis Oikonomou Giorgia Renga Andrea Casagrande Rossana G Iannitti Matteo Puccetti Cecilia Garlanda Soohyun Kim Suzhao Li Frank L van de Veerdonk Charles A Dinarello Luigina Romani |
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| Institution: | 1. Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.; 2. Istituto Superiore di Sanità, Roma, Italy.; 3. Humanitas Clinical and Research Center, Rozzano, Milan, Italy.; 4. Department of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America.; 5. Department of Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.; University of Wisconsin-Madison, United States of America, |
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| Abstract: | 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. |
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