beta-Glucan of Candida albicans cell wall causes the subversion of human monocyte differentiation into dendritic...

The functional consequences of treating human monocytes with purified and chemically characterized Candida albicans beta-glucan -- a major microbial pathogen associated molecular pattern -- on their differentiation into dendritic cells (DC) were investigated. We show here that beta-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 beta-glucan is a mixture of both beta-(1,3) and beta-(1,6) glucan, we investigated their relative contribution by the use of non-Candida beta-glucan structural analogs. We found that high molecular weight (MW) glucans beta-(1,6) pustulan and beta-(1,3) curdlan totally mimicked the effect of C. albicans beta-glucan, while the low MW beta-(1,3) glucan laminarin did not have any effect. Because beta-glucan is a common constituent of all fungi and is abundantly released in vivo during systemic fungal infection, this novel effect of beta-glucan has potential implications for host-parasite relationship in candidiasis and other mycoses. In particular, our data suggest that beta-glucan could bias noninfected, bystander monocytes, thus aggravating the general immunodeficiency, predisposing to systemic fungal infection.