beta-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 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.
Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. roberto.nisini@iss.it
Roberto
R
Nisini
Antonella
A
Torosantucci
Giulia
G
Romagnoli
Paola
P
Chiani
Simona
S
Donati
Maria Cristina
MC
Gagliardi
Raffaela
R
Teloni
Valeria
V
Sargentini
Sabrina
S
Mariotti
Egidio
E
Iorio
Antonio
A
Cassone
D017951:Antigen Presentation; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002473:Cell Wall / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000502:physiology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology*
D016207:Cytokines; D047071:beta-Glucans