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Differential effects of IL-17 pathway in disseminated candidiasis and zymosan-induced multiple organ failure
Critical Care volume 13, Article number: P30 (2009)
The role of the IL-17 pathway in fungal sepsis remains controversial. Several studies suggested that IL-17 is crucial for the protection against Candida sepsis, while 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.
IL-17 receptor-deficient (IL-17RA-/-) and control mice were intravenously infected with 2 × 105 CFU live C. albicans UC820 per mouse. Mortality, fungal loads in the kidneys, neutrophil recruitment and phagocytosis and killing were assessed. IL-17RA-/- and control mice were also assessed for mortality in a multiorgan failure sepsis model induced by the fungal component zymosan.
On the one hand, IL-17RA-/- mice showed increased mortality and higher fungal loads in the kidneys in the model of disseminated candidiasis. On the other hand, the absence of IL-17RA in the knockout mice did not protect the mice against the multiorgan failure induced by zymosan. Furthermore, no reduction in neutrophil recruitment and defects in phagocytosis and killing in the first few hours of Candida infection were found. A significantly lower TNF production in response to Candida in cells from IL-17RA-/- mice was observed.
These data demonstrate that the IL-17 pathway 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 during fungal sepsis. In addition, IL-17 deficiency does not appear to reflect a pure innate defect, since it did not result in loss of neutrophil recruitment and function during the first few hours of fungal sepsis. Furthermore, the lower TNF production in response to Candida in cells from IL-17RA-/- mice could contribute to susceptibility to disseminated candidiasis.