Human astrocytes inhibit Cryptococcus neoformans growth by a nitric oxide-mediated mechanism

Sunhee C. Lee, Dennis W Dickson, Celia F. Brosnan, Arturo Casadevall

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Cryptococcus neoformans is an opportunistic fungus that causes life-threatening meningoencephalitis in 5-10% of patients with acquired immune deficiency syndrome. Cryptococcal meningoencephalitis is characterized by a lymphohistiocytic infiltrate, accumulation of encapsulated forms of C. neoformans, and varying degrees of glial reaction. Little is known about the contribution of endogenous central nervous system cells to the pathogenesis of cryptococcal infections. In this study, we investigated the role of astrocytes as potential effector cells against C. neoformans. Primary cultures of human fetal astrocytes, activated with interleukin 1β plus interferon γ 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, NG-methyl-mono-arginine and NG-nitro-arginine methyl ester. The results suggest a novel function for human astrocytes in host defence and provide a precedent for the use of NO· as an antimicrobial effector molecule by human cells.

Original languageEnglish (US)
Pages (from-to)365-369
Number of pages5
JournalJournal of Experimental Medicine
Volume180
Issue number1
StatePublished - Jul 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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