IL-37 Inhibits Inflammasome Activation and Disease Severity in Murine Aspergillosis

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalPLoS Pathogens
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

ASJC Scopus subject areas

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology
  • Medicine(all)

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    Moretti, S., Bozza, S., Oikonomou, V., Renga, G., Casagrande, A., Iannitti, R. G., Puccetti, M., Garlanda, C., Kim, S., Li, S., van de Veerdonk, F. L., Dinarello, C. A., & Romani, L. (2014). IL-37 Inhibits Inflammasome Activation and Disease Severity in Murine Aspergillosis. PLoS Pathogens, 10(11). https://doi.org/10.1371/journal.ppat.1004462