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=5

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=<p>The effect of the anti-inflammatory cytokine interleukin-37 (IL-37) on host defense against <italic>Candida</italic> 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 <italic>Candida albicans</italic> pseudohyphae, macrophages from hIL-37Tg mice release 39% less TNFα compared to cells from wild-type (WT) mice (<italic>p</italic> = 0.01). <italic>In vivo</italic>, 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 WT mice. We conclude that IL-37 interferes with the innate protective anti-<italic>Candida</italic> host response by reducing the production of proinflammatory cytokines and suppressing neutrophil recruitment in response to <italic>Candida,</italic> resulting in an increased susceptibility to disseminated candidiasis.</p>