The in vitro fungicidal activity of human macrophages against Penicillium marneffei is suppressed by dexamethasone

- Dexamethasone decreases TNF-α yields of P. marneffei infected macrophages.
- Dexamethasone reduces acidification of P. marneffei conidia-containing phagosome.
- Dexamethasone enhances red pigment secretion after infected macrophages lysis.
- Our findings partly explain persistence of P. marneffei in immunosuppressed hosts.

Penicillium marneffei (P. marneffei) is a pathogenic fungus that can persist in macrophages and cause a life-threatening systemic mycosis in immunocompromised hosts. To elucidate the mechanisms underlying this opportunistic fungal infection, we established the co-culture system of P. marneffei conidia and human monocyte-derived macrophages (MDM) for investigating the interactions between them. And, we impaired the immune state of MDM by the addition of dexamethasone (DEX). Compared with immunocompetent MDM without DEX treatment in response to P. marneffei, DEX could damage MDM function in initiating the innate immune response through decreasing TNF-α production and the proportion of P. marneffei conidia in mature phagolysosomes, while the red pigment secretion by P. marneffei conidia was promoted by DEX following MDM lysis. Our data provide the evidence that DEX-treated MDM have a low fungicidal activity against P. marneffei that causes penicilliosis in immunocompromised hosts.