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Iron limitation and the gamma interferon-mediated antihistoplasma state of murine macrophages
T E Lane1, B A Wu-Hsieh, D H Howard
1Department of Microbiology and Immunology, University of California School of Medicine, Los Angeles 90024.
Abstract:
The zoopathogenic fungus Histoplasma capsulatum requires iron for growth. Intracellular growth of the fungus within mouse peritoneal macrophages is inhibited by recombinant murine gamma interferon (IFN-gamma). Such treatment of mouse peritoneal macrophages induces a marked downshift in transferrin receptors. We tested whether the antihistoplasma effect of IFN-gamma-treated macrophages is the result of iron deprivation. Treatment of mouse peritoneal macrophages with the intracellular iron chelator deferoxamine inhibits the intracellular growth of H. capsulatum. Exposure of macrophages to holotransferrin antagonizes the effect of both recombinant murine IFN-gamma and deferoxamine treatments. These results suggest that iron restriction may be one of the bases for the IFN-gamma-induced antihistoplasma effect of mouse macrophages.
Insights
Iron restriction inhibits Histoplasma capsulatum growth in macrophages. Gamma interferon (IFN-γ) triggers this iron deprivation, suggesting it underlies the antifungal effect against this fungus.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Histoplasma capsulatum is an opportunistic fungal pathogen.
- Iron is essential for fungal growth.
- Gamma interferon (IFN-γ) inhibits intracellular fungal growth in macrophages.
Purpose of the Study:
- To investigate if iron deprivation mediates the antifungal effect of IFN-γ on macrophages against H. capsulatum.
Main Methods:
- Macrophages were treated with recombinant murine IFN-γ or deferoxamine (an iron chelator).
- Intracellular growth of H. capsulatum was assessed.
- Effects of holotransferrin on fungal growth were evaluated.
Main Results:
- IFN-γ treatment of macrophages reduced transferrin receptor expression.
- Deferoxamine treatment inhibited intracellular H. capsulatum growth.
- Holotransferrin reversed the inhibitory effects of both IFN-γ and deferoxamine.
Conclusions:
- Iron restriction is a key mechanism behind the IFN-γ-induced inhibition of H. capsulatum in macrophages.
- Targeting iron availability presents a potential therapeutic strategy against histoplasmosis.