Candida albicans mannoprotein influences the biological function of dendritic cells.
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-alpha, 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 FcgammaR 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.
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06123 Perugia, Italy.
Donatella
D
Pietrella
Giovanni
G
Bistoni
Cristina
C
Corbucci
Stefano
S
Perito
Anna
A
Vecchiarelli
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017951:Antigen Presentation; D002176:Candida albicans / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000382:microbiology / Q000502:physiology*; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88; D017452:Receptors, IgG / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D017452:Receptors, IgG; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C025363:mannoproteins; D018664:Interleukin-12