Chloroquine Induces Human Mononuclear Phagocytes to Inhibit and Kill Cryptococcus neoformans by a Mechanism Independent of Iron Deprivation

Infections due to Cryptococcus neoformans are common in AIDS patients. We investigated the effect of chloroquine, which raises the pH of phagolysosomes, on the anticrypto-coccal activity of mononuclear phagocytes. C. neoformans multiplied within monocyte-derived macrophages (MDM) in the absence of chloroquine but were killed with the addi-tion of chloroquine. Ammonium chloride was also benefi-cial, suggesting that effects were mediated by alkalinizing the phagolysosome. Chloroquine inhibits growth of other in-tracellular pathogens by limiting iron availability. However, chloroquine-induced augmentation of MDM anticryptococ