AUTHOR=van de Veerdonk Frank L. , Gresnigt Mark S. , Oosting Marije , van der Meer Jos W. M. , Joosten Leo A. B. , Netea Mihai G. , Dinarello Charles A. TITLE=Protective host defense against disseminated candidiasis is impaired in mice expressing human interleukin-37 JOURNAL=Frontiers in Microbiology VOLUME=Volume 5 - 2014 YEAR=2015 URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2014.00762 DOI=10.3389/fmicb.2014.00762 ISSN=1664-302X ABSTRACT=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.