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

• Penicillium marneffei induced a rise in [Ca2+]c in human macrophages.
• Effect of [Ca2+]c on TNF-α production in P. marneffei-infected macrophages.
• Elevation of Ca2+ promotes phagosome maturation in P. marneffei-infected macrophages.
• Elevation of macrophage [Ca2+]c is associated with reduced survival of P. marneffei.

Increases in cytosolic Ca2+ concentration ([Ca2+]c) promote phagocyte antimicrobial responses. Here, we investigated macrophages stimulated by Penicillium marneffei (P. marneffei). [Ca2+]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 [Ca2+]c in human macrophages. Further, increased [Ca2+]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 [Ca2+]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 Ca2+ signaling may play an important role in controlling the replication of P. marneffei within macrophages.