Cytokine-induced fungicidal activity of human polymorphonuclear leukocytes against Penicillium marneffei

Abstract

We investigated the fungicidal activity of human polymorphonuclear leukocytes (PMN) against Penicillium marneffei. The yeast cells were cocultured in vitro with PMN for 24 h. Microscopic examination was also performed to examine the germination of yeast cells and their transformation to hyphal form during culture. Unstimulated PMN inhibited fungal growth when used at a higher effector/target (E/T) ratio but inhibited germination at a lower E/T ratio. We also examined the effects of various PMN-activating cytokines, including granulocyte-macrophage colony stimulating factor (GM-CSF), G-CSF, interleukin (IL)-8, interferon (IFN)-γ and tumor necrosis factor (TNF)-α on the activity of PMN. Among these, GM-CSF, G-CSF and IFN-γ enhanced PMN activity from being fungistatic to fungicidal. However, the other cytokines had little or no effect on PMN activity. In contrast, all tested cytokines enhanced PMN inhibitory effects on germination and morphological changes of P. marneffei. These antifungal activities were most strongly induced by GM-CSF. The combined use of any of the above cytokines failed to synergistically enhance antifungal PMN activity. Our results demonstrated that cytokine-activated PMN exert a significant antifungal activity, by suppressing the growth and germination of P. marneffei. Our results suggest that PMN may contribute to host resistance to infection against this fungal pathogen.