Beta-1,2-linked oligomannosides from Candida albicans act as signals for tumor necrosis factor alpha production

Different cell wall components from Candida albicans have been shown to stimulate murine macrophages for tumor necrosis factor alpha (TNF-alpha) secretion. All of these molecules contain beta-1,2-oligomannosides. In order to examine their role in TNF-alpha production, acid-labile oligosaccharides, released from C. albicans VW32 cell wall phosphopeptidomannan by mild acid hydrolysis, and previously shown to correspond to homopolymers of beta-1,2-linked mannopyranosyl units, were separated by gel filtration chromatography according to their degree of polymerization. Murine macrophages incubated with purified oligomannosides (M2 to M8) released TNF-alpha to an extent which was dependent on, although not directly correlated with, the length of the mannosyl chain. Slight activity was observed with M4 and M5; M6 and M7 had virtually no effect, whereas M8 was associated with strong TNF-alpha release. This effect of M8 was dose dependent and was not altered by polymyxin B, known to interfere with lipopolysaccharide-induced TNF-alpha production. These results suggest that stimulation of TNF-alpha release by C. albicans glycoconjugates containing beta-1,2-linked oligomannosides may be due, at least in part, to the presence of these components.