Cryptococcus neoformans infection in mice previously infected with LP-BM5 MuLV, the agent of murine AIDS (MAIDS)

Abstract

We studied susceptibility to experimental systemic cryptococcosis in mice previously infected with the retroviral complex LP-BM5 (responsible for murine AIDS). LP-BM5 was inoculated to C57B1/6 mice by intravenous (i.v.) injection 8 weeks before an i.v. challenge with 4 x 10(3) CFU of Cryptococcus neoformans. Uninfected and singly infected mice were used as controls. LP-BM5 infection did not result in a significant increase in fungal burdens in the lungs or brains of co-infected animals compared to mice infected with C. neoformans alone. However, mortality was enhanced in the co-infected animals. The kinetics of splenocyte subsets differed in co-infected mice and LP-BM5-infected mice; the increase in CD4+, CD8+ and Ly5+ cells was only moderate in the former. Cytokine production by concanavalin A (Con A)-stimulated splenocytes from co-infected mice showed a marked decrease in the Th1 response (IFN-gamma, IL-2) and an increase in the Th2 response (IL-4, IL-10). Furthermore, cryptococcosis altered the course of MAIDS, inhibiting splenomegaly. This effect was not related to a decrease in ecotropic virus titres in the spleen or to improved in vitro responsiveness of spleen cells to Con A. The marked decrease in IFN-gamma production in co-infected animals could partly explain the inhibition of LP-BM5-induced splenomegaly. This model of murine retroviral infection does not seem to be suitable for studying cryptococcosis in immunosuppressed animals, but remains valuable for investigating in vivo interactions between two pathogens.