Frontiers in Microbiology (Jan 2015)

Protective host defense against disseminated candidiasis is impaired in mice expressing human interleukin-37

  • Frank L. Van De Veerdonk,
  • Frank L. Van De Veerdonk,
  • Frank L. Van De Veerdonk,
  • Mark S Gresnigt,
  • Jos WM Van Der Meer,
  • Leo eJoosten,
  • Leo eJoosten,
  • Mihai eNetea,
  • Mihai eNetea,
  • Charles eDinarello,
  • Charles eDinarello

DOI
https://doi.org/10.3389/fmicb.2014.00762
Journal volume & issue
Vol. 5

Abstract

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The effect of the anti-inflammatory cytokine interleukin-37 (IL 37) on host defense against Candida infections remains unknown. We assessed the role of IL 37 in a murine model of disseminated candidiasis using mice transgenic for human IL 37 (hIL 37Tg). Upon exposure to C. albicans pseudohyphae, macrophages from hIL-37Tg mice release 39% less TNFα compared to cells from wild-type mice (P=0.01). In vivo, hIL 37Tg mice displayed a decreased capacity to recruit neutrophils to the site of infection. These defects were associated with increased mortality and organ fungal growth in hIL-37Tg compared to wild-type mice. We conclude that IL-37 interferes with the innate protective anti-Candida host response by reducing the production of proinflammatory cytokines and suppressing neutrophil recruitment in response to Candida, resulting in an increased susceptibility to disseminated candidiasis.

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