IL-37 inhibits inflammasome activation and disease severity in murine aspergillosis

• Published in: PLoS pathogens Vol. 10; no. 11; p. e1004462
• Main Authors: Moretti, Silvia, Bozza, Silvia, Oikonomou, Vasilis, Renga, Giorgia, Casagrande, Andrea, Iannitti, Rossana G, Puccetti, Matteo, Garlanda, Cecilia, Kim, Soohyun, Li, Suzhao, van de Veerdonk, Frank L, Dinarello, Charles A, Romani, Luigina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.11.2014; Public Library of Science (PLoS)
• Subjects: Animals; Aspergillosis; Biology and Life Sciences; Carrier Proteins - genetics; Carrier Proteins - immunology; Cystic fibrosis; Cytokines; Disease Models, Animal; Experiments; Female; Health aspects; Histology; Host-parasite relationships; Immune system; Infections; Inflammasomes - genetics; Inflammasomes - immunology; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Inflammatory bowel disease; Interleukin-1 - genetics; Interleukin-1 - immunology; Interleukin-1beta - genetics; Interleukin-1beta - immunology; Interleukins; Mice; Mice, Knockout; Microbiological research; NLR Family, Pyrin Domain-Containing 3 Protein; Physiological aspects; Proteins; Pulmonary Aspergillosis - genetics; Pulmonary Aspergillosis - immunology; Pulmonary Aspergillosis - pathology; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - immunology; Rodents; Transgenic animals
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1004462

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.