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Intracellular survival of Candida albicans in peritoneal macrophages from chronic peritoneal dialysis patients
Abstract:
Candidal peritonitis is a tenacious infection in patients undergoing chronic peritoneal dialysis. Since little is known about host defenses of the human peritoneal cavity against fungi, we investigated the interaction of peritoneal macrophages (PM phi) from uninfected dialysis patients with Candida albicans blastospores. Chemiluminescence (CL) techniques were used to assess the respiratory burst activity of these cells, and candidacidal activity was evaluated with a fluorochrome microassay. In sharp contrast to peripheral blood polymorphonuclear leukocytes (PMNs) from healthy donors, which gave a brisk luminol-enhanced CL response to opsonized blastospores and killed 35% of cell-associated organisms, PM phi produced barely detectable luminol-enhanced CL and killed only 13% of intracellular Candida. These findings appeared to be associated with a decreased level of myeloperoxidase in PM phi. The mechanism of intracellular survival of C albicans also appeared to be related to relatively poor triggering of superoxide production during phagocytosis of viable blastospores. The CL response of PMNs to C albicans was opsonin-dependent, and peritoneal dialysis effluent was devoid of opsonic activity. These studies suggest that local cellular and humoral mechanisms of defense are inadequate for protection of peritoneal dialysis patients against candidal peritonitis.
Insights
Peritoneal macrophages in dialysis patients show impaired defense against Candida albicans, leading to poor fungal killing. Dialysis fluid lacks immune factors, increasing candidal peritonitis risk.
Area of Science:
- Immunology
- Microbiology
- Nephrology
Background:
- Candidal peritonitis is a severe complication in chronic peritoneal dialysis patients.
- Host defense mechanisms in the human peritoneal cavity against fungal infections are poorly understood.
Purpose of the Study:
- To investigate the interaction between peritoneal macrophages (PM phi) from dialysis patients and Candida albicans.
- To assess the candidacidal activity and respiratory burst of these macrophages.
Main Methods:
- Chemiluminescence (CL) techniques were used to measure respiratory burst activity.
- A fluorochrome microassay evaluated candidacidal activity.
- Comparison of peritoneal macrophages with peripheral blood polymorphonuclear leukocytes (PMNs) from healthy donors.
Main Results:
- Peritoneal macrophages (PM phi) exhibited significantly lower luminol-enhanced CL and killed fewer Candida cells (13%) compared to PMNs (35%).
- Reduced myeloperoxidase levels and poor superoxide production were observed in PM phi during phagocytosis.
- Peritoneal dialysis effluent lacked opsonic activity, which is crucial for PMN response to Candida.
Conclusions:
- Local cellular and humoral defense mechanisms in the peritoneal cavity are inadequate in dialysis patients.
- These deficiencies contribute to the susceptibility of patients to candidal peritonitis.