Nramp1 gene affects selective early steps in macrophage-mediated anti-cryptococcal defense

Cryptococcus neoformans is an opportunistic fungus responsible for severe a nd often recurrent meningoencephalitis in immunodepressed patients. Initial evidence suggests that C. neoformans is a facultative intracellular pathog en; however, the strategies by which C. neoformans undergoes survival and e ventually proliferation have not been elucidated. We investigated the role of Nramp1 gene in macrophage-mediated anticryptococcal defense. Using cell lines expressing the functional, mutated or knockout gene, it was establish ed that Nramp1 (1) is not involved in the phagocytic event, (2) influences anti-cryptococcal activity in the early steps but not at later times, and ( 3) is unrelated to the biomolecular pathways through which C. neoformans im pairs macrophage secretory response. Although the functional role of Nramp1 is still far from being elucidated, the present data add insight into its involvement in macrophage-mediated antimicrobial defense, particularly in t he initial steps allowing C. neoformans growth inhibition.