Differential effects of IL-17 pathway in disseminated candidiasis and zymosan-induced multiple organ failure.
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.
van de Veerdonk
Frank L
FL
Department of Medicine, Radboud University Nijmegen Medical Centre, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Kullberg
Bart Jan
BJ
Verschueren
Ineke C
IC
Hendriks
Thijs
T
van der Meer
Jos W M
JW
Joosten
Leo A B
LA
Netea
Mihai G
MG
D000818:Animals; D002177:Candidiasis / Q000276:immunology* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan / Q000633:toxicity*
D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D015054:Zymosan