Variable Tnf-α Production By Murine Macrophages to a Cell Wall Extract of Candida Albicans

Murine peritoneal macrophages respond to Candida albicans challenge with the production of the inflammatory cytokine, tumor necrosis factor α (TNF-α). Since mannan is a component of the fungal cell wall that has been indentified as an important virulence factor in the pathogenicity of C. albicans, we examined its ability to stimulate macrophages to produce TNF-α. Mannan was extracted from the yeast phase of C. albicans, purified, and was shown to contain mannose by acid hydrolysis and paper chromatography. Murine peritoneal (PMφ) and alveolar (AMφ) macrophages were collected and treated with varying concentrations (0.05-1000 μg/ml) of mannan. Controls included LPS-treated cells and inhibition studies using 2% D-mannose and methyl-α-D-mannopyranoside. TNF-α concentrations were measured using the L929 fibroblast assay. With mannan alone, both PMφ and AMφ responded with production of TNF-α in a dose-dependent manner. Preincubation with 100 U/ml interferon-γ (IFN-γ for 3 h4 pimed macrophages for enhanced TNF-α production. This data indicated that both PMφ and AMφ responded to the combination of IFN-γ and mannan with production of significantly different amounts of TNF-α. While the results of this study suggest that mannan alone can induce a macrophage response, the nature of the responding macrophage (PMφ or AMφ) determines the final outcome of cytokine production