C-type lectin interactions with Schistosoma mansoni SEA : Molecular basis and function
Liempt, P.A.G. van
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Outline of this thesis The studies described in this thesis have been performed to gain more insight in the recognition of Schistosoma mansoni glycans by C-type lectins and the consequences for dendritic cell mediated immune responses. As a first approach to understand the molecular interactions of schistosome glycans and dendritic cells that lead to TH2 cell polarization, the recognition of schistosome glycan antigens by DCs were investigated. In chapter 2 and 3 we describe the carbohydrate specificity of DC-SIGN and MGL respectively, by performing a glycan array using an Fc-chimera. Next, the molecular basis of differences in carbohydrate binding properties of DC-SIGN and its homologue L-SIGN were investigated in chapter 4. The interaction of DC-SIGN with self- glycoproteins was analyzed in chapter 5, by determining the DC-SIGN ligands that are crucial for the adhesion and rolling of dendritic cells on endothelial cells, a prerequisite for migration of DCs to the lymph node. The interactions of DC-SIGN with glycolipids of different life stages of the human parasite Schistosoma mansoni were investigated in chapter 6. In chapter 7 we demonstrate that Schistosoma mansoni soluble egg antigens are recognized by several C-type lectins on dendritic cells and suppress TLR- induced DC maturation. Finally, the results presented in this thesis are integrated in a general discussion and main perspectives for future studies are discussed in chapter 8.