Christine M.C. Bank

Specificity of DC-SIGN for mannose- and fucose-containing glycans.

The dendritic cell specific C‐type lectin dendritic cell specific ICAM‐3 grabbing non‐integrin (DC‐SIGN) binds to “self” glycan ligands found on human cells and to “foreign” glycans of bacterial or parasitic pathogens. Here, we investigated the binding properties of DC‐SIGN to a large array of potential ligands in a glycan array format. Our data indicate that DC‐SIGN binds with K d < 2 μM to a neoglycoconjugate in which Galβ1‐4(Fucα1‐3)GlcNAc (Lex) trisaccharides are expressed multivalently. A lower selective binding was observed to oligomannose‐type N‐glycans, diantennary N‐glycans expressing Lex and GalNAcβ1‐4(Fucα1‐3)GlcNAc (LacdiNAc‐fucose), whereas no binding was observed to N‐glycans expressing core‐fucose linked either α1‐6 or α1‐3 to the Asn‐linked GlcNAc of N‐glycans. These results demonstrate that DC‐SIGN is selective in its recognition of specific types of fucosylated glycans and subsets of oligomannose‐ and complex‐type N‐glycans.

Interaction of Schistosome Glycans with the Host Immune System

Schistosomiasis is a parasitic disease caused by trematodes that affects more than 200 million people worldwide, mostly children in developing countries. Annually, 200 000 deaths are estimated to be associated with schistosomiasis (van der Werf et al., 2002). Until now, attempts to control infection and disease have mostly failed but the disease can be effectively treated by chemotherapy (Praziquantel ). One of the most striking features of schistosomiasis is that the worms are experts in modulation and evasion of the host immune response, to enable their survival, migration and development in different host tissues. It is becoming increasingly clear that schistosome glycoconjugates play a crucial role in the evasion mechanisms that are exploited by the parasites. Here we will summarize our studies that aim to increase our molecular understanding of the role of specific schistosome glycan antigens in immune modulation. We will focus on the interactions of schistosome glycans with the host immune system that result in the mounting of T helper cell 2 (Th2) responses.