Colony counts, scanning electron microscopy, and light microscopy were used to assess the capacity of Candida albicans to colonize (naturally) and infect the alimentary tract of adult and neonatal (athymic [nu/nu] or heterozygous [+/nu] littermates) germfree BALB/c mice. When exposed to yeast-phase C. albicans, the alimentary tract of adult germfree mice (nu/nu or +/nu) is quickly (within 24 to 48 h) colonized with yeast cells. Neither morbidity nor mortality was evident in any mice that were colonized with a pure culture of C. albicans for 6 months. Yeast cells of C. albicans predominated on mucosal surfaces in the oral cavities and vaginas of adult athymic and heterozygous mice. In both genotypes, C. albicans hyphae were observed in keratinized tissue on the dorsal posterior tongue surface and in the cardial-atrium section of the stomach. Conversely, neonatal athymic or heterozygous mice, born to germfree or C. albicans-colonized mothers, do not become heavily colonized or infected with C. albicans until 11 to 15 days after birth. Although yeast cells adhered to some mucosal surfaces in vivo, neither widespread mucocutaneous candidiasis, i.e., invasion of mucosal surfaces with C. albicans hyphae, nor overwhelming systemic candidiasis was evident in neonatal (nu/nu or +/nu) mice. Thus, even in the absence of functional T-cells and a viable bacterial flora, athymic and heterozygous littermate mice (adult or neonatal BALB/c) that are colonized with a pure culture of C. albicans manifest resistance to extensive mucocutaneous and systemic candidiasis.

Congenitally immunodeficient nude (nulnu) mice and their immunocompetent littermates (nul+) were used to determine whether the absence of thymus-matured T cells would alter the capacity of Cryptococcus neoformans to colonize their mucosal surfaces or enhance their susceptibility to systemic cryptococcosis, or both, following oral challenge. We present data demonstrating that an encapsulated strain of C. neoformans serotype A colonized the alimentary tracts of germfree, conventional, and antibiotic-treated conventional nulnu mice. Scanning electron microscopy showed that C. neoformans adhered to the epithelial surfaces of the oral cavities, esophagi, and gastrointestinal tracts of monoassociated nulnu and nul+ mice, and culture data showed that there were more viable C. neoformans cells in the alimentary tracts of nulnu mice than of nul+ mice. Tetracycline-treated conventional nulnu, but not nul+, mice were also colonized with C. neoformans following intragastric challenge. C. neoformans-monoassociated and tetracycline-treated conventional nulnu mice succumbed to disseminated cryptococcosis with cerebral involvement 3 to 4 weeks after oral challenge, whereas no mortality was observed for similarily challenged nul+ mice. These results demonstrate that an encapsulated strain of C. neoformans can colonize mucosal surfaces and cause systemic cryptococcosis in immunodeficient nulnu mice, suggesting that the alimentary tract can be a portal of entry for C. neoformans in an immunodeficient host. These data also indicate that functional T cells play an important role in resistance to systemic cryptococcosis of endogenous origin.