IFN-γ Is Required for IL-12 Responsiveness in Mice with Candida albicans Infection

To elucidate the role of IFN-γ in antifungal CD4+ Th-dependent immunity, 129/Sv/Ev mice deficient for IFN-γ receptor (IFN-γR−/−) were assessed for susceptibility to gastrointestinal or systemic Candida albicans infection and for parameters of innate and adaptive T helper immunity. IFN-γR−/− mice failed to mount protective Th1-mediated acquired immunity upon mucosal immunization or in response to a live vaccine strain of the yeast. The impaired Th1-mediated resistance correlated with defective IL-12 responsiveness, but not IL-12 production, and occurred in the presence of an increased innate antifungal resistance. The development of nonprotective Th2 responses was observed in IFN-γR−/− mice upon mucosal infection and subsequent reinfection. However, under experimental conditions of Th2 cell activation, the occurrence of Th2 cell responses was similar in IFN-γR−/− and in IFN-γR+/+ mice. These results indicate the complex immunoregulatory role of IFN-γ in the induction of mucosal and nonmucosal anticandidal Th cell responses; IFN-γ is not essential for the occurrence of Th2 responses but is required for development of IL-12-dependent protective Th1-dependent immunity.