Differential effects of IL-17 pathway in disseminated candidiasis and zymosan-induced multiple organ failure.

Abstract

The role of the IL-17 pathway in antifungal host defense is controversial. Several studies suggested that IL-17 is crucial for the protection against Candida infection, whereas other studies reported that IL-17 may contribute to inflammatory pathology and worsening of fungal disease. To address these discrepancies, we assessed the differential role of IL-17 pathway in two models of fungal sepsis: intravenous infection with live Candida albicans, in which fungal growth is the main cause of mortality, and zymosan-induced multiple organ failure, in which the inflammatory pathology drives the mortality. First, IL-17 receptor-deficient (IL-17RA) mice showed increased mortality and higher fungal loads in the kidneys in the model of disseminated candidiasis, partly caused by lower neutrophil recruitment in the IL-17RA mice. Second, IL-17RA mice were not protected against the multiorgan failure induced by zymosan. These data demonstrate that IL-17 does not have a major contribution to the inflammatory pathology leading to organ failure in fungal sepsis and support the concept that the IL-17 pathway is protective in antifungal host defense.