Differential susceptibility of yeast and hyphal forms of Candida albicans to macrophage-derived nitrogen-containing compounds

Abstract

Candida albicans is a dimorphic fungus capable of transition from the yeast form (Y-Candida) to the hyphal form (H-Candida). Both Y-Candida and H- Candida are known to be growth inhibited by murine macrophages (Mφ) in vitro. In the present report, we demonstrate that Mφ exposed to interferon gamma (IFN-γ) plus lipopolysaccharide (LPS) show enhanced anti-Y-Candida and anti-H-Candida activities. To further investigate the phenomenon, Y-Candida and H-Candida were assessed for susceptibilities to Mφ-derived supernatants. Only the growth of H-Candida, and not that of Y-Candida, is impaired by cell- free supernatants from Mφ treated with IFN-γ plus LPS. In contrast, no H- Candida growth inhibition occurs when supernatants from Mφ exposed to IFN- γ plus LPS in the presence of N(G)-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, are employed. Finally, supernatants from Mφ incubated with sodium nitroprusside, an NO-generating agent, also show anti- H-Candida activity. In conclusion, these results indicate that H-Candida but not Y-Candida is susceptible to extracellular antifungal mechanisms employed by Mφ, which likely involve stable nitrogen-containing compounds.