IFN-GAMMA IS REQUIRED FOR IL-12 RESPONSIVENESS IN MICE WITH CANDIDA-ALBICANS INFECTION

To elucidate the role of IFN-gamma in antifungal CD4(+) Th-dependent i mmunity, 129/Sv/Ev mice deficient for IFN-gamma receptor (IFN-gamma R- /-) were assessed for susceptibility to gastrointestinal or systemic C andida albicans infection and for parameters of innate and adaptive T helper immunity. IFN-gamma R-/- mice failed to mount protective Th1-me diated acquired immunity upon mucosal immunization or in response to a live vaccine strain of the yeast, The impaired Th1-mediated resistanc e correlated with defective IL-12 responsiveness, but not IL-12 produc tion, and occurred in the presence of an increased innate antifungal r esistance. The development of nonprotective Th2 responses was observed in IFN-gamma R-/- mice upon mucosal infection and subsequent reinfect ion. However, under experimental conditions of Th2 cell activation, th e occurrence of Th2 cell responses was similar in IFN-gamma R-/- and i n IFN-gamma R+/+ mice. These results indicate the complex immunoregula tory role of IFN-gamma in the induction of mucosal and nonmucosal anti candidal Th cell responses; IFN-gamma is not essential far the occurre nce of Th2 responses but is required for development of IL-li-dependen t protective Th1-dependent immunity.