Protein-calorie malnutrition impairs host defense against Candida albicans

Protein-calorie malnutrition (PCM) impairs immune responsiveness predisposing to Candida albicans sepsis, but mechanisms are unclear. This study examined the effect of PCM on enteric-derived C. albicans intestinal translocation and the ability of in vivo interferon-gamma (IFN-gamma) to upregulate macrophage (MO) candidacidal mechanisms in PCM mice. Control (24% casein) and low protein (2.5%) diets were given for 4 weeks. Mice (n = 160) were fed C. albicans in their drinking water for 3 days and C. albicans translocation (mean colony-forming units (CFU)/g tissue +/- SEM) to the GI tract, liver, spleen, and kidney was assessed at 1 and 5 days following endotoxin challenge of 1, 5, and 10 mg/kg body wt. In a separate study (n = 100 mice), IFN-gamma (1000-10,000 U/day ip) vs saline was given for 3 days prior to harvesting peritoneal macrophages for assay of superoxide anion (O2-), percentage macrophage phagocytosis of C. albicans, and percentage killing of C. albicans. On Day 1, fungal translocation to the intestinal wall and systemic organs in the PCM group was significantly higher. On Day 5, mean CFU were significantly higher in the PCM group, indicating impaired organ clearance. Mean O2-, phagocytosis, and killing were significantly impaired in the PCM group (P less than 0.05), but IFN-gamma improved all functions. PCM significantly depressed host responses to C. albicans. IFN-gamma treatment enhanced candidacidal mechanisms, suggesting a therapeutic role in the malnourished host predisposed to C. albicans sepsis.