Cell wall components of fungi involved in induction of host immune response are predominantly proteins and glycoproteins, the latter being mainly mannoproteins (MP). In this study we analyse the interaction of the MP from Candida albicans (MP65) with dendritic cells (DC) and demonstrate that MP65 stimulates DC and induces the release of TNF-α, IL-6 and the activation of IL-12 gene, with maximal value 6 h post treatment. MP65 induces DC maturation by increasing costimulatory molecules and decreasing CD14 and Fc γ R molecule expression. The latter effect is partly mediated by toll-like receptor 2 (TLR2) and TLR4, and the MyD88-dependent pathway is involved in the process. MP65 enables DC to activate T cell response, its protein core is essential for induction of T cell activation, while its glycosylated portion primarily promotes cytokine production. The mechanisms involved in induction of protective response against C. albicans could be mediated by the MP65 antigen, suggesting that MP65 may be a suitable candidate vaccine.
Candida albicans mannoprotein influences the biological function of dendritic cells
PIETRELLA, Donatella;BISTONI, GIOVANNI;CORBUCCI, CRISTINA;PERITO, Stefano;VECCHIARELLI, Anna
2006
Abstract
Cell wall components of fungi involved in induction of host immune response are predominantly proteins and glycoproteins, the latter being mainly mannoproteins (MP). In this study we analyse the interaction of the MP from Candida albicans (MP65) with dendritic cells (DC) and demonstrate that MP65 stimulates DC and induces the release of TNF-α, IL-6 and the activation of IL-12 gene, with maximal value 6 h post treatment. MP65 induces DC maturation by increasing costimulatory molecules and decreasing CD14 and Fc γ R molecule expression. The latter effect is partly mediated by toll-like receptor 2 (TLR2) and TLR4, and the MyD88-dependent pathway is involved in the process. MP65 enables DC to activate T cell response, its protein core is essential for induction of T cell activation, while its glycosylated portion primarily promotes cytokine production. The mechanisms involved in induction of protective response against C. albicans could be mediated by the MP65 antigen, suggesting that MP65 may be a suitable candidate vaccine.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.