Early resistance of interleukin-10 knockout mice to acute systemic candidiasis

In contrast to immunocompetent controls, interleukin-10 (IL-10) knockout (K O) mice eliminated an experimental intravenous inoculation with Candida alb icans from their kidneys. Improved clearance of C. albicans from the kidney s of IL-10 KO mice was evident at 24 h after intravenous challenge with the fungus. Conversely, mice with a deletion of the IL-4 cytokine gene were mo re susceptible to systemic candidiasis than were immunocompetent controls. The hyperresistance of IL-10 KO mice to acute systemic candidiasis did not seem to correlate with nitric oxide-mediated immunity, but rather, it appea red to be associated with more efficient effector function of innate cells, possibly neutrophils. In support of the latter hypothesis, we observed tha t neutrophils from IL-10 KO mice were more efficient at killing C. albicans blastoconidia and hyphae than were neutrophils from immunocompetent contro l mice. Neither IL-10 KO nor IL-4 KO mice that were monoassociated,vith C. albicans for 4 weeks showed any histologic evidence of systemic candidiasis of endogenous origin. In contrast to systemic candidiasis, we observed no significant (P < 0.05) differences in susceptibility among IL-10 KO, IL-4 K O, and wild-type (immunocompetent) mice to orogastric candidiasis. Our resu lts suggest that IL-10 exerts a negative effect on the early, innate respon se to acute systemic candidiasis; however, in comparison to immunocompetent control (wild-type) mice, neither IL-10 nor IL-4 deficiency enhanced susce ptibility to orogastric candidiasis.