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Enhancement of macrophage candidacidal activity by interferon-gamma
1Department of Pediatrics, University School of Medicine, Debrecen, Hungary.
Abstract:
In previous studies, we have reported that opsonized candida species are ingested by monocytes and monocyte-derived macrophages (MDM), but uptake of unopsonized candida is mediated only by MDM, primarily through the mannose receptor (MR). This study examines the effects of recombinant IFN-gamma on the uptake and killing of unopsonized C. albicans by MDM. We report here that MDM treated with IFN-gamma developed an increase in their capacity to ingest and kill unopsonized C. albicans and to release O2- upon stimulation with candida. Mannan (0.1 to 5 mg/ml) inhibited uptake of candida in a dose-dependent manner, but glucan (5 mg/ml) did not. These data suggest that mannose receptors may be involved in the increased phagocytosis and killing of unopsonized candida by human macrophages treated with IFN-gamma.
Insights
Interferon-gamma enhances the ability of human monocyte-derived macrophages (MDM) to ingest and kill unopsonized Candida albicans. This increased phagocytosis is likely mediated by mannose receptors, suggesting a new therapeutic target.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Monocyte-derived macrophages (MDM) phagocytose opsonized Candida species.
- Uptake of unopsonized Candida by MDM primarily involves the mannose receptor (MR).
- The role of IFN-gamma in this process requires further investigation.
Purpose of the Study:
- To investigate the effects of recombinant IFN-gamma on the phagocytosis and killing of unopsonized Candida albicans by MDM.
- To elucidate the mechanism underlying IFN-gamma-mediated enhancement of Candida clearance.
Main Methods:
- MDM were treated with recombinant IFN-gamma.
- Phagocytosis and killing assays using unopsonized C. albicans were performed.
- Superoxide anion (O2-) release upon Candida stimulation was measured.
- Inhibition assays using mannan and glucan were conducted.
Main Results:
- IFN-gamma treatment significantly increased MDM's capacity to ingest and kill unopsonized C. albicans.
- IFN-gamma-treated MDM exhibited enhanced O2- release upon Candida stimulation.
- Mannan dose-dependently inhibited Candida uptake, while glucan did not.
Conclusions:
- Recombinant IFN-gamma enhances the phagocytic and microbicidal activity of human MDM against unopsonized C. albicans.
- The findings suggest a significant role for mannose receptors in IFN-gamma-induced enhancement of phagocytosis and killing of Candida.
- IFN-gamma may represent a therapeutic agent to boost macrophage defense against Candida infections.