Schistosoma mansoni egg glycoproteins : glycan structures and host immune responses

Leiden Repository

Schistosoma mansoni egg glycoproteins : glycan structures and host immune responses

Title: Schistosoma mansoni egg glycoproteins : glycan structures and host immune responses
Author: Meevissen, Moniek Hubertina Joanna
Publisher: Division of Glycobiology and Glyco-immunology of Parasitic infections, Department of Parasitology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2012-06-13
Keywords: Antigen-presenting cells
C-type lectins
Glycoproteins
Glycosylation
Granuloma formation
Mass spectrometry
Schistosoma mansoni
T helper 2 polarization
Abstract: 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/α1 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/α1 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.
Description: Promotores: A.M. Deelder, M. Yazdanbakhsh, Co-Promotor: C.H. Hokke
With Summary in Dutch
Faculty: LUMC
Citation: Meevissen, M.H.J., 2012, Doctoral Thesis, Leiden University
ISBN: 9789461821089
Sponsor: J.E. Jurriaanse stichting Beckman Coulter
Handle: http://hdl.handle.net/1887/19067
 

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