Schistosoma mansoni egg glycoproteins : glycan structures and host immune responses

Meevissen, M.H.J. (2012)

Doctoral Thesis

Schistosomes are parasitic helminths that cause chronic infections in over 200 million people in tropical and sub-tropical areas around the world. Glycoproteins from the eggs of the parasite Schistosoma mansoni induce various immune responses in the human host, including T-cell modulation and granuloma formation. Three major, immunogenic egg glycoproteins have been identified; omega-1, IPSE/_1 and kappa-5. The studies in this thesis have unraveled structural and molecular details of the interaction between these three glycoproteins and innate immune cells of the host. Firstly, we have studied the structural details of the N-glycans expressed on these three glycoproteins. Most notably, omega-1 and IPSE/_1 carry diantennary N-glycans which mainly display Lewis X motifs, while kappa-5 expresses triantennary N-glycans with LDN motifs. Then, we have investigated the interaction of the egg glycoproteins with C-type lectin receptors on antigen-presenting immune cells. We show that specific glycan motifs on the egg glycoproteins determine differential binding to these lectin receptors. Finally, we have investigated functional effects of omega-1 and kappa-5. We show that the Th2-modulating capacity of omega-1 is dependent on both glycan-lectin interactions as well as its RNase activity. We found that kappa-5 contains granuloma-inducing properties, which are partly mediated by its LDN motifs.

• T helper 2 polarization
• Schistosoma mansoni
• Mass spectrometry
• Granuloma formation
• Glycosylation
• Glycoproteins
• C-type lectins
• Antigen-presenting cells

• All authors: Meevissen, M.H.J.
• Supervisor: Deelder, A.M.; Yazdanbakhsh, M.
• Co-supervisor: Hokke, C.H.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2012-06-13
• ISBN (print): 9789461821089
• Sponsorship: J.E. Jurriaanse stichting Beckman Coulter