Germ-free C57BL/6 x 129 interferon-gamma knockout (IFN-gamma(-/-)) mic
e and their immunocompetent (+/-, +/+) counterparts were colonized wit
h a pure culture of Candida albicans to assess their natural susceptib
ility to mucosal and systemic candidiasis of endogenous origin. Coloni
zation with a pure culture of C. albicans was not lethal for adult or
neonatal IFN-gamma(-/-) gnotobiotic mice over the 15-week study. The I
FN-gamma(-/-) mice were more susceptible to gastric (cardia-antrum sec
tion), anorectal, and acute systemic (intravenous challenge) candidias
is than immunocompetent controls, and some IFN-gamma(-/-) mice develop
ed intestinal adenomas after colonization with C. albicans. The enhanc
ed susceptibility of IFN-gamma(-/-) mice, compared with immunocompeten
t controls, may be associated with a poor proliferative response of sp
leen cells to C. albicans antigens and a T helper 2 (IgG1) serum antib
ody response to C. albicans antigens. Thus, IFN-gamma is important for
murine resistance to gastric, anorectal, and acute systemic candidias
is.