Characteristics of invasive candidiasis in gamma interferon- and interleukin-4-deficient mice:: Role of macrophages in host defense against Candida albicans

Murine models of invasive candidiasis were used to study the in vivo importance of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) in host defense against Candida albicans and to characterize the tissue inflammatory reactions, with special reference to macrophages (M phi). Knockout (KO) IFN-gamma-deficient (GKO) and IL-4-deficient (IL-4 KO) and C57BL/6 parental mouse strains were challenged intraperitoneally with 10(8) C. albicans blastoconidia, Survival of GKO mice was significantly lower (16.7%) than that of C57BL/6 control (55.5%) and IL-4 KO (61.1%) animals, but was not correlated with the extent of organ colonization, Immunohistological analysis with a panel of myeloid and lymphoid markers revealed multiple renal abscesses, myocarditis, hepatitis, meningoencephalitis, and pneumonia in each strain, with a dominant presence of M phi. In the absence of IFN-gamma, C. albicans induced striking changes in the phenotype of alveolar M phi and extensive perivascular lymphoid infiltrates in the lung, Impairment in nitric oxide production by peritoneal M phi was shown only in GKO mice, and they produced Candida-specific immunoglobulin G (IgG), IgM, IgA, and IgG subclasses in lower titers, Our in vivo studies with KO mice elucidate a critical role for IFN-gamma, but not IL-4, in host defense against C. albicans.