Alteration of polymorphonuclear leukocyte activity by viable Candida albicans
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Abstract:
The response of human polymorphonuclear leukocytes (PMN) to blastospores and pseudo-hyphae of the opportunistic fungus Candida albicans has been studied in vitro and in vivo. Of the fungicidal mechanisms elucidated thus far, the myeloperoxidase-hydrogen peroxide-halide system appears to be most effective against cells of this fungus. In our studies on the interaction between murine PMN and blastospores, we assayed the release of H2O2 by PMN incubated with viable or killed, unopsonized or opsonized blastospores by using two assay systems, lysis of murine erythrocytes and oxidation of scopoletin. Our results showed that PMN released increasing amounts of H2O2 when incubated with increasing numbers of opsonized or unopsonized killed blastospores, but released decreasing amounts of H2O2 when incubated with increasing numbers of opsonized or unopsonized viable blastospores. The oxidative metabolic burst by PMN in the presence of viable or killed blastospores was also measured by using reduction of nitroblue tetrazolium and chemiluminescence. Viable blastospores stimulated a stronger metabolic burst than killed blastospores, suggesting that PMN respond to live blastospores more vigorously than killed blastospores; however, live blastospores appear to alter or inhibit the release of H2O2 by PMN.
Insights
Human white blood cells (polymorphonuclear leukocytes or PMN) release more hydrogen peroxide (H2O2) when encountering killed Candida albicans. Live fungi trigger a stronger overall response but paradoxically reduce H2O2 release.
Area of Science:
- Immunology
- Mycology
- Microbiology
Background:
- Candida albicans is an opportunistic fungal pathogen.
- Human polymorphonuclear leukocytes (PMN) are key immune cells involved in fighting fungal infections.
- The myeloperoxidase-hydrogen peroxide-halide system is a primary fungicidal mechanism.
Purpose of the Study:
- To investigate the in vitro and in vivo response of PMN to Candida albicans blastospores.
- To quantify hydrogen peroxide (H2O2) release by PMN upon interaction with viable and killed C. albicans.
- To assess the oxidative metabolic burst of PMN in response to C. albicans.
Main Methods:
- Murine PMN were incubated with viable or killed, opsonized or unopsonized C. albicans blastospores.
- Hydrogen peroxide (H2O2) release was measured using erythrocyte lysis and scopoletin oxidation assays.
- Oxidative metabolic burst was assessed via nitroblue tetrazolium reduction and chemiluminescence.
Main Results:
- PMN released increasing amounts of H2O2 with increasing numbers of killed C. albicans blastospores.
- PMN released decreasing amounts of H2O2 with increasing numbers of viable C. albicans blastospores.
- Viable C. albicans induced a stronger oxidative metabolic burst than killed blastospores, yet appeared to inhibit H2O2 release.
Conclusions:
- PMN exhibit a complex response to C. albicans, with viable fungi modulating H2O2 release.
- The interaction dynamics suggest that live C. albicans may evade or interfere with key PMN fungicidal mechanisms.
- Further research is needed to fully elucidate the mechanisms of PMN- C. albicans interaction and host defense.