HUMAN MICROGLIA MEDIATE ANTI-CRYPTOCOCCUS NEOFORMANS ACTIVITY IN THE PRESENCE OF SPECIFIC ANTIBODY

The interaction of the opportunistic fungus Cryptococcus neoformans wi th human microglia was studied in vitro in the presence and absence of capsule binding antibody. In the absence of capsule binding antibody there was little or no phagocytosis. Addition of the murine monoclonal antibody (mAb) 2H1 (IgG1, kappa) to the capsular glucuronoxylomannan (GXM) produced a dose-dependent enhancement of C. neoformans phagocyto sis by microglia. Phagocytosis resulted in marked inhibition of fungal proliferation. Microglial antifungal activity was studied by colony f orming unit assay, L-[H-3]leucine incorporation assay, and phase contr ast microscopy. At microglia: C. neoformans ratios of 10:1 to 80:1 fun gal growth was reduced by 61-95%. Inhibitors of nitric oxide synthase and reactive oxygen intermediates did not prevent antifungal activity mediated by human microglia. Transmission electron microscopic studies revealed that although some internalized yeast cells were killed, the majority were intact consistent with fungistasis. Human microglia cel ls are potent effector cells against C. neoformans in vitro in the pre sence of specific antibody. Enhancement of microglial activity in vivo by opsonins may be a useful therapeutic strategy.