Saccharomyces cerevisiae‐ and Candida albicans‐Derived Mannan Induced Production of Tumor Necrosis Factor Alpha by Human Monocytes in a CD14‐ and Toll‐Like Receptor 4‐Dependent Manner

The cytokine‐inducing activities of fungal polysaccharides were examined in human monocytes in culture, with special reference to CD14 and Toll‐like receptors (TLRs). Tumor necrosis factor alpha (TNF‐α) production by monocytes was markedly induced in a dose‐dependent manner upon stimulation with cell walls from Candida albicans and mannan from Saccharomyces cerevisiae and C. albicans, although relatively high concentrations (10 to 100 μg/ml) of stimulants were required for activation as compared with the reference lipopolysaccharide (LPS) (1 to 10 ng/ml). The yeast form C. albicans and its mannan and cell wall fractions exhibited higher TNF‐α production than respective preparations from the hyphal form. Only slight TNF‐α production was induced by the S. cerevisiae glucan. The TNF‐α production triggered by reference LPS and purified fungal mannans required the presence of LPS‐binding protein (LBP), and these responses were inhibited by anti‐CD14 and anti‐TLR4 antibodies, but not by anti‐TLR2 antibody. In contrast to the activity of LPS, the activity of purified S. cerevisiae mannan was not inhibited by polymyxin B. These findings suggested that the mannan‐LBP complex is recognized by CD14 on monocytes and that signaling through TLR4 leads to the production of proinflammatory cytokines in a manner similar to that induced by LPS.