Colonization and pathogenesis of Cryptococcus neoformans in gnotobiotic mice

Congenitally immunodeficient nude (nu/nu) mice and their immunocompetent littermates (nu/+) 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 nu/nu mice. Scanning electron microscopy showed that C. neoformans adhered to the epithelial surfaces of the oral cavities, esophagi, and gastrointestinal tracts of monoassociated nu/nu and nu/+ mice, and culture data showed that there were more viable C. neoformans cells in the alimentary tracts of nu/nu mice than of nu/+ mice. Tetracycline-treated conventional nu/nu, but not nu/+, mice were also colonized with C. neoformans following intragastric challenge. C. neoformans-monoassociated and tetracycline-treated conventional nu/nu mice succumbed to disseminated cryptococcosis with cerebral involvement 3 to 4 weeks after oral challenge, whereas no mortality was observed for similarily challenged nu/+ mice. These results demonstrate that an encapsulated strain of C. neoformans can colonize mucosal surfaces and cause systemic cryptococcosis in immunodeficient nu/nu 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.