Dendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, the ability to activate DCs is considered a key tool to enhance the efficacy and quality of vaccination. Here we report a novel immunomodulatory sulfolipid named beta-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune response in vivo. Beta-SQDG18 induces maturation of DC with the upregulation of MHC II molecules and co-stimulatory proteins (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-gamma). Mice immunized with OVA associated to beta-SQDG18 (1:500) produced a titer of anti-OVA Ig comparable to traditional adjuvants. In an experimental model of melanoma, vaccination of C57BL/6 mice with beta-SQDG18-adjuvanted hgp10 peptide elicited a protective response with a reduction in tumour growth and increase in survival.
A new marine-derived sulfoglycolipid triggers dendritic cell activation and immune adjuvant response
Manzo E;Cutignano A;Pagano D;Gallo C;Nuzzo G;Fontana A
2017
Abstract
Dendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, the ability to activate DCs is considered a key tool to enhance the efficacy and quality of vaccination. Here we report a novel immunomodulatory sulfolipid named beta-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune response in vivo. Beta-SQDG18 induces maturation of DC with the upregulation of MHC II molecules and co-stimulatory proteins (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-gamma). Mice immunized with OVA associated to beta-SQDG18 (1:500) produced a titer of anti-OVA Ig comparable to traditional adjuvants. In an experimental model of melanoma, vaccination of C57BL/6 mice with beta-SQDG18-adjuvanted hgp10 peptide elicited a protective response with a reduction in tumour growth and increase in survival.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.