Susceptibility of congenitally immunodeficient mice to a nonencapsulated strain of Cryptococcus neoformans

The susceptibility of congenitally immunodeficient mice to a nonencapsulated strain of Cryptococcus neoformans (strain M7) was evaluated. Gnotobiotic mice with defined congenital defects in innate immunity (beige) or cell-mediated immunity (athymic) or with combined defects in innate and cellular immunity (beige athymic) were i.v. challenged with C. neoformans M7. The nonencapsulated strain of C. neoformans produced a persistent low-grade infection in the brains of all immunodeficient and immunocompetent mice used in this study. Immunocompetent mice (nu/+;bg/+) and immunodeficient bg/bg mice readily cleared nonencapsulated cryptococci from their kidneys, liver, lungs, and spleen. In contrast to nu/+ mice, nu/nu mice had a reduced capacity to clear nonencapsulated cryptococci from their kidneys and liver after i.v. challenge. Both bg/bg-nu/nu and bg/bg-nu/+ mice developed a low-grade infection in their kidneys, liver, lungs, and spleen, which was maintained throughout the 21-day study. Persistent infections were not due to reversion to an encapsulated state. These data indicate that a capsule may not always be necessary for C. neoformans to survive, in vivo, in tissues of immunodeficient and immunocompetent mice.