PLoS Pathogens (Nov 2014)

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

DOI
https://doi.org/10.1371/journal.ppat.1004462
Journal volume & issue
Vol. 10, no. 11
p. e1004462

Abstract

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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.