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

Abstract

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.

NADPH oxidase of human dendritic cells: Role in Candida albicans killing and regulation by interferons, dectin‐1 and CD206

“…To investigate the receptors involved in NADPH oxidase activation, DC were stimulated with purified biglycan, glucan and Pam 3 CSK4, specific agonists of CD206, dectin-1 and TLR2, respectively [44][45][46]. We found that biglycan and Pam 3 CSK4, alone or in combination, did not activate ROS production (Fig.…”

From Secretome Analysis to Immunology

“…that are sensed by dendritic cells. TLRs have been implicated in the sensing of fungal polysaccharides by monocytes (8,9) and dendritic cells (10). However, there are very few examples in which the TLR involved in fungal polysaccharide recognition has been characterized (11).…”

Genetic analysis of innate immunity in resistance to Candida albicans

“…70 TLR2 and TLR4 are the most well characterized of the TLRs with respect to their involvement in fungal recognition. TLR4, which is expressed on the surface of macrophages, DCs, and endothelial cells, 71,72 recognizes C. albicans-derived mannan, 73 possibly in conjunction with the CD14 receptor. It is involved in the control of fungal replication in the kidneys, likely by inducing the secretion of CXC cytokines such as KC and MIP-2, which subsequently recruit neutrophils to the site of infection.…”