DC-SIGN mediates binding of dendritic cells to authentic pseudo-LewisY glycolipids of Schistosoma mansoni cercariae, the first parasite-specific ligand of DC-SIGN

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Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation

In schistosomiasis, a parasitic disease caused by helminths, the parasite eggs induce a T helper 2 cell (T(H)2) response in the host. Here, the specific role of human monocyte-derived dendritic cells (DCs) in initiation and polarization of the egg-specific T cell responses was examined. We demonstrate that immature DCs (iDCs) pulsed with schistosome soluble egg antigens (SEA) do not show an increase in expression of co-stimulatory molecules or cytokines, indicating that no conventional maturation was induced. The ability of SEA to affect the Toll-like receptor (TLR) induced maturation of iDCs was examined by copulsing the DCs with SEA and TLR-ligands. SEA suppressed both the maturation of iDCs induced by poly-I:C and LPS, as indicated by a decrease in co-stimulatory molecule expression and production of IL-12, IL-6 and TNF-alpha. In addition, SEA suppressed T(H)1 responses induced by the poly-I:C-pulsed DCs, and skewed the LPS-induced mixed response towards a T(H)2 response. Immature DCs rapidly internalized SEA through the C-type lectins DC-SIGN, MGL and the mannose receptor and the antigens were targeted to MHC class II-positive lysosomal compartments. The internalization of SEA by multiple C-type lectins may be important to regulate the response of the iDCs to TLR-induced signals

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)<2muM to a neoglycoconjugate in which Galbeta1-4(Fucalpha1-3)GlcNAc (Le(x)) trisaccharides are expressed multivalently. A lower selective binding was observed to oligomannose-type N-glycans, diantennary N-glycans expressing Le(x) and GalNAcbeta1-4(Fucalpha1-3)GlcNAc (LacdiNAc-fucose), whereas no binding was observed to N-glycans expressing core-fucose linked either alpha1-6 or alpha1-3 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

DC-SIGN mediates adhesion and rolling of dendritic cells on primary human umbilical vein endothelial cells through LewisY antigen expressed on ICAM-2

Immature dendritic cells (DCs) are recruited from blood into tissues to patrol for foreign antigens. After antigen uptake and processing, DCs mature and migrate to the secondary lymphoid organs where they initiate immune responses. DC-SIGN is a DC-specific C-type lectin that acts both as a pattern recognition receptor and as an adhesion molecule. As an adhesion molecule, DC-SIGN is able to mediate rolling and adhesion over endothelial cells under shear flow. In this study, we show that the binding partner of DC-SIGN on endothelial cells is the glycan epitope Lewis(Y) (Le(Y)), expressed on ICAM-2. The interaction between DC-SIGN on dendritic cells and ICAM-2 on endothelial cells is strictly glycan-specific. ICAM-2 expressed on CHO cells only served as a ligand for DC-SIGN when properly glycosylated, underscoring its function as a scaffolding protein. The expression of Le(Y) in endothelial cells is directed by the enzyme FUT1. Silencing of FUT1 results in a decrease in the rolling and adhesion of immature DCs over endothelial cells. The identification of Le(Y) as the carbohydrate ligand of DC-SIGN in endothelial cells opens new possibilities for the manipulation of DC migratio

Luanda-Holanda; irregular migration from Angola to the Netherlands

Against the backdrop of push-pull and social network theories on migration and criminological theory on human smuggling, this article tries to answer the questions of why and how Angolan asylum-seekers migrated to the Netherlands since the end of the 1990s. The study shows that the migrants can be described as opportunity seeking migrants, rather than survival migrants. Most migrants made no use of typical human smugglers during their travel. They rather used assistance from their social network and made use of the services of middlemen, called esquemas, on an ad-hoc basis. In this article it is argued that "archetypal" large smuggling organisations in Angola have not evolved because of the existence of these highly informal networks. Support is found that both push-pull and social network theories can contribute to explaining irregular, asylum migration. © 2008 The Author. Journal Compilation © 2008 IOM