β-Glucan of Candida albicans cell wall causes the subversion of human monocyte differentiation into dendritic cells

The functional consequences of treating human monocytes with purified and chemically characterized Candida albicans β‐glucan—a major microbial pathogen associated molecular pattern—on their differentiation into dendritic cells (DC) were investigated. We show here that β‐glucan‐treated monocytes differentiated into mature DC (Glu‐MoDC) with altered phenotype and functional behavior, similarly to DC derived from C. albicans germ‐tubes‐infected monocytes (Gt‐MoDC). They failed to express CD1a and to up‐regulate CD80 and DR molecules. Moreover, they produced IL‐10 but not IL‐12 and primed naive T cells without inducing their functional polarization into effector cells. Since C. albicans β‐glucan is a mixture of both β‐(1,3) and β‐(1,6) glucan, we investigated their relative contribution by the use of non‐Candida β‐glucan structural analogs. We found that high molecular weight (MW) glucans β−(1,6) pustulan and β‐(1,3) curdlan totally mimicked the effect of C. albicans β‐glucan, while the low MW β‐(1,3) glucan laminarin did not have any effect. Because β‐glucan is a common constituent of all fungi and is abundantly released in vivo during systemic fungal infection, this novel effect of β‐glucan has potential implications for host‐parasite relationship in candidiasis and other mycoses. In particular, our data suggest that β‐glucan could bias noninfected, bystander monocytes, thus aggravating the general immunodeficiency, predisposing to systemic fungal infection.