Antifungal type 1 responses are upregulated in IL-10-deficient mice

C57BL/b mice are highly resistant to infections caused by Candida albicans and Aspergillus fumigatus. To elucidate the role of IL-10 produced by C57BL /b mice during these infections, parameters of infection and immunity to it were evaluated in IL-10-deficient and wild-type mice with disseminated or gastrointestinal candidiasis or invasive pulmonary aspergillosis. Unlike pa rasitic protozoan infection, C. albicans or A. fumigatus infection did not induce significant acute toxicity in IL-10-deficient mice, who, instead, sh owed reduced fungal burden and fungal-associated inflammatory responses. Th e increased resistance to infections as compared to wild-type mice was asso ciated with upregulation of innate and acquired antifungal Th1 responses, s uch as a dramatically higher production of IL-12, nitric oxide (NO) and TNF -alpha as well as IFN-gamma by CD4(+) T cells. Pharmacological inhibition o f NO production greatly reduced resistance to gastrointestinal candidiasis, thus pointing to the importance of IL-10-dependent NO regulation at mucosa l sites in fungal infections. These results are reminiscent of those obtain ed in genetically susceptible mice, in which IL-10 administration increased , and IL-10 neutralization decreased, susceptibility to C. albicans and A. fumigatus infections. Collectively, these observations indicate that the ab sence of IL-10 augments innate and acquired antifungal immunity by upregula ting type 1 cytokine responses. The resulting protective Th1 responses lead to a prompt reduction of fungal growth, thus preventing tissue destruction and lethal levels of proinflammatory cytokines. (C) 1999 Editions scientif iques et medicales Elsevier SAS.