title: Protective host defense against disseminated candidiasis is impaired in mice expressing human interleukin-37.
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 Candida albicans pseudohyphae, macrophages from hIL-37Tg mice release 39% less TNFα compared to cells from wild-type (WT) 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 WT 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.
authors.affiliation: Department of Medicine, University of Colorado Denver Denver, CO, USA ; Department of Medicine, Radboud University Nijmegen Medical Center Nijmegen, Netherlands ; Radboud Center for Infection Nijmegen, Netherlands.
authors.forename: Frank L
authors.initials: FL
authors.lastname: van de Veerdonk
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Center Nijmegen, Netherlands.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gresnigt
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Center Nijmegen, Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Oosting
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Center Nijmegen, Netherlands.
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Center Nijmegen, Netherlands ; Radboud Center for Infection Nijmegen, Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Center Nijmegen, Netherlands ; Radboud Center for Infection Nijmegen, Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Medicine, University of Colorado Denver Denver, CO, USA ; Department of Medicine, Radboud University Nijmegen Medical Center Nijmegen, Netherlands.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
keywords: Candida; IL-1F7; IL-37; TNFα; antifungal host defense; inflammation; neutrophils