Targeting DC-SIGN with carbohydrate multivalent systems.

Abstract

DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin), a C-type lectin mainly present at the surface of immature dendritic cells, plays a relevant role activating and tailoring adaptive immune responses against different pathogens. This lectin recognizes, in a multivalent and calcium-dependent manner, highly glycosylated proteins present at the surface of pathogens. Several groups have devoted remarkable efforts to develop carbohydrate multivalent compounds targeting this lectin to modulate its role in pathogen capture and in the generation of an immune response. Most of these approaches have been based on mannosylation of immunogenic proteins such as ovalbumin but new strategies have been envisaged to achieve these goals. Although mannosylated systems cannot provide the required selectivity for a specific lectin at dendritic cells, fucosylated compounds have overcome this problem specifically targeting DC-SIGN and avoiding interferences with other lectins, such as the mannose receptor. The use of these carbohydrate multivalent compounds to target DC-SIGN can be considered a promising strategy to inhibit pathogen entry and to develop new vaccines against pathogen infection or cancer. New studies are required to provide more insights into the complex immune pathway involving DC-SIGN.