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.