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Histoplasma capsulatum inhibits apoptosis and Mac-1 expression in leucocytes
A I Medeiros1, V L D Bonato, A Malheiro
1Department of Clinical Analyses, Toxicology and Bromatology, School of Pharmaceutical Sciences of Ribeirão Preto, SP, Brazil.
Abstract:
Histoplasma capsulatum is a fungus found intracellularly in neutrophils and peripheral blood mononuclear cells (PBMCs), suggesting that it is capable of evading damage and survives inside these cells. In this study, we report that neutrophils from H. capsulatum-infected mice, and human neutrophils and mononuclear cells exposed to H. capsulatum presented less apoptosis than those from noninfected animals or cells exposed to medium only. Moreover, cells harvested from infected animals are resistant to apoptosis induced by dexamethasone - a proapoptotic stimulant. We also show that neutrophils harvested from infected mice and PBMCs from humans exposed to the fungus had a greatly decreased Mac-1 expression. We conclude that H. capsulatum induces an antiapoptotic state on leucocytes, which correlates with decreased cell-surface Mac-1 expression. These facts may represent an escape mechanism for the fungus by delaying cell death and allowing the fungus to survive inside leucocytes.
Insights
Histoplasma capsulatum infection reduces white blood cell (leukocyte) apoptosis, enhancing fungal survival. This antiapoptotic effect correlates with decreased Mac-1 expression on these immune cells.
Area of Science:
- Mycology
- Immunology
- Cell Biology
Background:
- Histoplasma capsulatum is an intracellular fungal pathogen.
- It resides within neutrophils and peripheral blood mononuclear cells (PBMCs).
- Fungal survival suggests evasion of host cell damage.
Purpose of the Study:
- To investigate the effect of H. capsulatum infection on leukocyte apoptosis.
- To determine if H. capsulatum influences the expression of Mac-1 on leukocytes.
- To elucidate potential fungal escape mechanisms.
Main Methods:
- Exposure of mouse neutrophils and human leukocytes to H. capsulatum.
- Assessment of apoptosis rates in infected vs. uninfected cells.
- Induction of apoptosis using dexamethasone.
- Measurement of Mac-1 expression on cell surfaces.
Main Results:
- H. capsulatum-infected leukocytes exhibited reduced apoptosis compared to controls.
- Infected cells showed resistance to dexamethasone-induced apoptosis.
- A significant decrease in Mac-1 expression was observed on infected neutrophils and PBMCs.
Conclusions:
- H. capsulatum induces an antiapoptotic state in leukocytes.
- This antiapoptotic effect is linked to reduced Mac-1 expression.
- These findings suggest a fungal survival strategy involving delayed leukocyte death.