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Candidacidal activity of monocyte-derived human macrophages: relationship between Candida killing and oxygen radical
Abstract:
Freshly isolated human monocytes ingested and killed Candida albicans, and generated O2- H2O2 and .OH efficiently. When monocytes were cultured in vitro, these cells transformed into macrophages. Cultured monocytes retained their ingestive activity but lost their candidacidal activity almost completely after day 3. The release of O2- by monocytes decreased slightly with culture and that of .OH was markedly decreased on day 3 of culture. The activity of myeloperoxidase in the monocytes decreased with culture. These results suggested that the loss of candidacidal activity is due to the decrease of .OH generation and myeloperoxidase activity in cultured monocytes.
Insights
Freshly isolated human monocytes effectively kill Candida albicans by generating reactive oxygen species. However, in vitro culture leads to macrophages that lose this candidacidal activity due to reduced hydroxyl radical (.OH) generation and myeloperoxidase activity.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Human monocytes are crucial immune cells involved in pathogen defense.
- Candida albicans is a common fungal pathogen that can cause opportunistic infections.
- Monocyte-derived macrophages play a significant role in innate immunity.
Purpose of the Study:
- To investigate the candidacidal activity of human monocytes and their in vitro-derived macrophages.
- To determine the changes in reactive oxygen species (ROS) generation and myeloperoxidase (MPO) activity during monocyte-to-macrophage differentiation.
- To elucidate the mechanisms underlying the loss of candidacidal activity in cultured monocytes.
Main Methods:
- Isolation of human monocytes from peripheral blood.
- In vitro culture of monocytes to induce differentiation into macrophages.
- Assessment of Candida albicans ingestion and killing by monocytes and macrophages.
- Measurement of superoxide (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (.OH) generation.
- Assay of myeloperoxidase (MPO) activity.
Main Results:
- Freshly isolated monocytes efficiently ingested and killed Candida albicans, producing O2-, H2O2, and .OH.
- In vitro cultured monocytes transformed into macrophages, retaining phagocytic capacity but losing candidacidal activity by day 3.
- ROS generation, particularly .OH, decreased significantly in cultured monocytes.
- Myeloperoxidase (MPO) activity also declined during in vitro culture.
Conclusions:
- The loss of candidacidal activity in cultured human monocytes is primarily attributed to diminished .OH generation and reduced MPO activity.
- Monocyte differentiation into macrophages in vitro alters their microbicidal mechanisms.
- Understanding these changes is vital for developing strategies to enhance antifungal immunity.