Candida albicanssuppresses nitric oxide (NO) production by interferon-gamma (IFN-γ) and lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages

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Abstract
We examined the in vitro effect of Candida albicans on NO production by macrophages. Candida albicans suppressed not only NO production but also expression of inducible NO synthase (iNOS) mRNA by murine IFN-γ and bacterial LPS-stimulated peritoneal macrophages. The suppression was not associated with inhibition but rather stimulation of IL-1β production. This effect was observed when more than 1 × 103/ml of Candida albicans were added to macrophage cultures (1 × 106 cells/ml) and reached a maximal level at 1 × 106/ml. The NO inhibitory effect of Candida albicans was mediated predominantly by as yet unidentified soluble factor(s) and to a lesser extent by direct contact. In addition, heat- or paraformaldehyde-killed Candida albicans did not show this inhibitory activity. Culture supernatant of Candida albicans also inhibited NO production by activated macrophages in a dose-dependent manner, and increased IL-1β production. Finally, the inhibitory effect was not mediated by IL-10 and transforming growth factor-beta (TGF-β), since neutralizing antibodies to these cytokines did not influence Candida albicans-induced reduction in macrophage NO production. Our results suggest that Candida albicans may evade host defence mechanism(s) through a soluble factor-mediated suppression of NO production by stimulated macrophages, and that the effect is independent of production of immunosuppressive cytokines such as IL-10 and TGF-β.