Reduced host resistance and Th1 response to<i>Cryptococcus neoformans</i>in interleukin-18 deficient mice

Using interleukin (IL)-18 deficient (IL-18−/−) mice, we examined the role of IL-18 in the host resistance and Th1 response against infection with Cryptococcus neoformans. Fungal clearance in the lung was reduced in IL-18−/− mice, although there was no significant change in the level of dissemination to the brain. The DTH response, as determined by footpad swelling, was also diminished in IL-18−/− mice compared to control wild-type (WT) mice. The levels of IL-12 and interferon (IFN)-γ in the sera were significantly lower in IL-18−/− mice than in WT mice. Spleen cells from infected WT mice produced a high level of IFN-γ upon stimulation with the microbe, while only a low level of IFN-γ production was detected in spleen cells from infected IL-18−/− mice. Administration of IL-18 almost completely restored the reduced response in IL-18−/− mice, while IL-12 showed a marginal effect. These results demonstrated the important role of IL-18 in the resistance and Th1 response of mice to C. neoformans by potentiating the production of IFN-γ.