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Cytokine-induced fungicidal activity of human polymorphonuclear leukocytes against Penicillium marneffei
N Kudeken1, K Kawakami, A Saito
1The First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, Japan.
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)-gamma and tumor necrosis factor (TNF)-alpha on the activity of PMN. Among these, GM-CSF, G-CSF and IFN-gamma 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.
Insights
Human immune cells called polymorphonuclear leukocytes (PMN) show fungicidal activity against Penicillium marneffei. Cytokines like GM-CSF enhance PMN
Area of Science:
- Immunology
- Mycology
- Cell Biology
Background:
- Penicillium marneffei is an emerging fungal pathogen causing infections in humans.
- Human polymorphonuclear leukocytes (PMN) are key immune cells involved in combating infections.
- The fungicidal mechanisms of PMN against P. marneffei are not fully understood.
Purpose of the Study:
- To investigate the fungicidal activity of human PMN against Penicillium marneffei.
- To determine the effect of PMN-activating cytokines on PMN antifungal activity.
- To elucidate the role of PMN in host resistance to P. marneffei infection.
Main Methods:
- In vitro co-culture of P. marneffei yeast cells with human PMN.
- Microscopic examination of yeast germination and hyphal transformation.
- Assessment of PMN activity with and without various cytokines (GM-CSF, G-CSF, IL-8, IFN-gamma, TNF-alpha).
Main Results:
- Unstimulated PMN inhibited fungal growth and germination in a dose-dependent manner.
- Granulocyte-macrophage colony stimulating factor (GM-CSF), G-CSF, and IFN-gamma enhanced PMN activity from fungistatic to fungicidal.
- All tested cytokines enhanced PMN's inhibitory effects on P. marneffei germination and morphology, with GM-CSF showing the strongest effect.
- Combined cytokine use did not result in synergistic enhancement of PMN antifungal activity.
Conclusions:
- Cytokine-activated PMN exhibit significant antifungal activity against P. marneffei by suppressing growth and germination.
- PMN, particularly when activated by cytokines like GM-CSF, play a crucial role in host defense against P. marneffei infections.
- These findings highlight the potential of PMN-based therapies for managing P. marneffei infections.
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