Differential role of IL‐18 and IL‐12 in the host defense against disseminated Candida albicans infection

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Abstract
IFN‐γ plays a crucial role in the defense against infection with Candida albicans. Since IL‐18 and IL‐12 are strong stimuli of IFN‐γ production, we investigated whether endogenous IL‐18 and IL‐12 are involved in the host defense during disseminated candidiasis. IL‐18 knockout (IL‐18‐/‐) mice, but not IL‐12‐/‐ mice, displayed an increased mortality due to C. albicans infection, accompanied by a decreased clearance of the yeasts from the kidneys late during the course of infection. Histopathology of the organs, combined with phagocyte recruitment experiments, showed a decreased influx of monocytes at the sites of Candida infection, mainly in the IL‐18‐/‐ mice. Whereas production of the chemokine KC was decreased in both IL‐18‐/‐ and IL‐12‐/‐ mice, MIP‐2 production was deficient only in IL‐18‐/‐ animals, which may explain the differences in phagocyte recruitment. In addition, although IFN‐γ production capacity, as a parameter of the Th1‐protective immunity, was reduced by 65 to 80% in the IL‐12‐/‐ mice, this defect was even more pronounced in the IL‐18‐/‐ mice (85 to 95% downmodulation). In conclusion, the anticandidal effects of endogenous IL‐18 are mediated late during the infection by assuring a proper IFN‐γ response and promoting the infiltration of the site of infection by monocytes.

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