HUMAN ASTROCYTES INHIBIT CRYPTOCOCCUS-NEOFORMANS GROWTH BY A NITRIC OXIDE-MEDIATED MECHANISM

Cryptococcus neoformans is an opportunistic fungus that causes life-th reatening meningoencephalitis in 5-10% of patients with acquired immun e deficiency syndrome. Cryptococcal meningoencephalitis is characteriz ed by a lymphohistiocytic infiltrate, accumulation of encapsulated for ms of C. neoformans, and varying degrees of glial reaction. Little is known about the contribution of endogenous central nervous system cell s to the pathogenesis of cryptococcal infections. In this study, we in vestigated the role of astrocytes as potential effector cells against C. neoformans. Primary cultures of human fetal astrocytes, activated w ith interleukin 1 beta plus interferon gamma inhibited the growth of C . neoformans. The inhibition of C. neoformans growth was paralleled by production of nitrite, and reversed by the inhibitors of nitric oxide (NO.) synthase, N-G-methyl-mono-arginine and N-G-nitro-arginine methy l ester. The results suggest a novel function for human astrocytes in host defence and provide a precedent for the use of NO. as an antimicr obial effector molecule by human cells.