CRYPTOCOCCUS-NEOFORMANS INHIBITS NITRIC-OXIDE PRODUCTION BY MURINE PERITONEAL-MACROPHAGES STIMULATED WITH INTERFERON-GAMMA AND LIPOPOLYSACCHARIDE

We examined the effect of Cryptococcus neoformans on nitric oxide (NO) production by activated cultured macrophages. C. neoformans suppresse d NO production by murine peritoneal macrophages stimulated with bacte rial lipopolysaccharide (LPS) and interferon (IFN)-gamma, while it did not influence the production of IL-1 beta. This effect was observed w hen 1 X 10(6) or 10(7) of C. neoformans was added to macrophage cultur es. A direct contact of C. neoformans with macrophages was essential f or this inhibitory effect, since placement of a 0.45-mu m-pore membran e between the organism and macrophages prevented such effect. In addit ion, C. neoformans killed by heat or paraformaldehyde did not shaw thi s inhibitory activity. Capsular polysaccharide did not mediate the inh ibitory effect, since two nonencapsulated mutant strains of C. neoform ans showed an inhibitory activity similar to that of encapsulated wild strains, and culture supernatants of C. neoformans, rich in polysacch aride antigens, did not inhibit macrophage NO production compared with control culture medium. The inhibitory effect was also not mediated b y interleukin (IL)-10 and transforming growth factor (TGF)-beta since neutralizing specific antibodies to these cytokines did not influence C. neoformans-induced reductions in macrophage NO production. Our resu lts suggest that C. neoformans may cause a direct suppression of NO-me diated fungicidal activity of macrophages, and the effect is independe nt of the capsular polysaccharide and production of IL-10 and TGF-beta . (C) 1997 Academic Press.