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Modulation of the macrophage oxidative burst by Histoplasma capsulatum
Abstract:
The production of reactive oxygen species by phagocytic cells is an important host defense against invading microorganisms. Because pathogens that achieve intracellular survival escape destruction by reactive oxidants, we investigated the relationship between the intracellular survival of H. capsulatum and the macrophage oxidative burst. H. capsulatum yeast failed to stimulate the release of reactive oxygen metabolites in unprimed murine macrophages despite extensive phagocytosis of the microorganisms. This effect was observed with live as well as heat-killed fungi over a wide range of yeast-to-macrophage ratios. Preincubation of murine macrophages with heat-killed H. capsulatum (but not with latex spheres), followed by incubation with unopsonized zymosan, resulted in inhibition of oxidative burst triggering without inhibition of zymosan phagocytosis. Ingestion of H. capsulatum yeast opsonized with the cognate mouse antibody resulted in significant oxidant release, suggesting that suppression of the respiratory burst may be circumvented through Fc-mediated phagocytosis.
Insights
Histoplasma capsulatum (H. capsulatum) evades macrophage defenses by suppressing the oxidative burst. However, antibody opsonization can restore reactive oxygen species release, aiding pathogen destruction.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Phagocytic cells produce reactive oxygen species (ROS) as a crucial defense mechanism against microbial pathogens.
- Intracellular pathogens that evade ROS-mediated destruction can lead to persistent infections.
Purpose of the Study:
- To investigate the interaction between intracellular survival of Histoplasma capsulatum (H. capsulatum) and the macrophage oxidative burst.
- To determine if H. capsulatum actively suppresses the macrophage respiratory burst.
Main Methods:
- Murine macrophages were incubated with live or heat-killed H. capsulatum yeast.
- The release of reactive oxygen metabolites was measured.
- Macrophages were preincubated with H. capsulatum before stimulation with zymosan.
- Phagocytosis and oxidative burst were assessed with and without antibody opsonization.
Main Results:
- Unprimed murine macrophages failed to release significant reactive oxygen metabolites upon phagocytosis of H. capsulatum, irrespective of viability or yeast-to-macrophage ratio.
- Preincubation with H. capsulatum inhibited the oxidative burst triggered by zymosan, without affecting zymosan phagocytosis.
- Antibody opsonization of H. capsulatum led to significant oxidant release, indicating Fc-mediated phagocytosis can overcome suppression.
Conclusions:
- H. capsulatum actively suppresses the macrophage oxidative burst, contributing to its intracellular survival.
- Fc-mediated phagocytosis represents a mechanism to circumvent H. capsulatum-induced suppression of the respiratory burst.