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

J Leukoc Biol. 2007 Nov;82(5):1136-42. doi: 10.1189/jlb.0307160. Epub 2007 Jul 26.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Candida albicans / immunology*
  • Candidiasis / immunology
  • Candidiasis / metabolism
  • Candidiasis / pathology
  • Cell Differentiation*
  • Cell Proliferation
  • Cell Wall / immunology
  • Cell Wall / metabolism*
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / cytology*
  • Dendritic Cells / physiology
  • Humans
  • Monocytes / cytology*
  • Monocytes / physiology
  • Phenotype
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • beta-Glucans / pharmacology*

Substances

  • Cytokines
  • beta-Glucans