Role of intracellular free calcium in killing Penicillium marneffei within human macrophages

Abstract Increases in cytosolic Ca 2+ concentration ([Ca 2+ ] c ) promote phagocyte antimicrobial responses. Here, we investigated macrophages stimulated by Penicillium marneffei ( P. marneffei ). [Ca 2+ ] c was determined in macrophages loaded with the fluorescent calcium probe Fura 2/AM as they were stimulated by P. marneffei . We found that P. marneffei induced an increase in [Ca 2+ ] c in human macrophages. Further, increased [Ca 2+ ] c with the ionophore A23187 promoted phagosomal acidification and maturation and reduced intracellular replication of P. marneffei in P. marneffei -infected human macrophages, whereas decreased [Ca 2+ ] c with the chelation MAPTAM decreased TNF-α production, inhibited phagosomal acidification and maturation and increased intracellular replication of P. marneffei . These data indicate that Ca 2+ signaling may play an important role in controlling the replication of P. marneffei within macrophages.