-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 -glucan—a major microbial pathogen associated molecular pattern—on their differentiation into dendritic cells (DC) were investigated. We show here that -glucan-treated monocytes differentiated into mature DC (Glu-MoDC) with altered phenotype and functional behavior, similarly to DC derived from C. 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 -glucan is a mixture of both -(1,3) and -(1,6) glucan, we investigated their relative contribution by the use of non-Candida -glucan structural analogs. We found that high molecular weight (MW) glucans (1,6) pustulan and -(1,3) curdlan totally mimicked the effect of C. albicans -glucan, while the low MW -(1,3) glucan laminarin did not have any effect. Because -glucan is a common constituent of all fungi and is abundantly released in vivo during systemic fungal infection, this novel effect of -glucan has potential implications for a host-parasite relationship in candidiasis and other mycoses. In particular, our data suggest that -glucan could bias noninfected, bystander monocytes, thus aggravating the general immunodeficiency, predisposing them to systemic fungal infection. J. Leukoc. Biol. 82: 000–000; 2007.