Glycomic analysis of life stages of the human parasite Schistosoma mansoni reveals developmental expression profiles of functional and antigenic glycan motifs

Authors Organisations
  • Cornelis H. Smit(Author)
    Leiden University Medical Center
  • Angela van Diepen(Author)
    Leiden University Medical Center
  • D. Linh Nguyen(Author)
    Leiden University Medical Center
  • Manfred Wuhrer(Author)
    Leiden University Medical Center
  • Karl Hoffmann(Author)
  • André M Deelder(Author)
    Leiden University Medical Center
  • Cornelis H. Hokke(Author)
    Leiden University Medical Center
Type Article
Original languageEnglish
Pages (from-to)1750-1769
JournalMolecular and Cellular Proteomics
Volume14
Issue number7
DOI
Publication statusPublished - 16 Apr 2015
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Abstract

Glycans present on glycoproteins and glycolipids of the major human parasite Schistosoma mansoni induce innate as well as adaptive immune responses in the host. To be able to study the molecular characteristics of schistosome infections it is therefore required to determine the expression profiles of glycans and antigenic glycan-motifs during a range of critical stages of the complex schistosome lifecycle. We performed a longitudinal profiling study covering schistosome glycosylation throughout worm- and egg-development using a mass spectrometry-based glycomics approach. Our study revealed that during worm development N-glycans with Galβ1-4(Fucα1-3)GlcNAc (LeX) and core-xylose motifs were rapidly lost after cercariae to schistosomula transformation, while GalNAcβ1-4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to two weeks of schistosomula development, while glycolipids with mono- and multi-fucosylated LDN-motifs remained present up to the adult worm stage. In contrast, expression of complex O-glycans diminished to undetectable levels within days after transformation. During egg development, a rich diversity of N-glycans with fucosylated motifs was expressed, but with α3-core fucose and a high degree of multi-fucosylated antennae only in mature eggs and miracidia. N-glycan antennae were exclusively LDN-based in miracidia. O-glycans in the mature eggs were also diverse and contained LeX- and multi-fucosylated LDN, but none of these were associated with miracidia in which we detected only the Galβ1-3(Galβ1-6)GalNAc core glycan. Immature eggs also exhibited short O-glycan core structures only, suggesting that complex fucosylated O-glycans of schistosome eggs are derived primarily from glycoproteins produced by the sub-shell envelope in the developed egg. Lipid glycans with multi-fucosylated GlcNAc repeats were present throughout egg development, but with the longer highly fucosylated stretches enriched in mature eggs and miracidia. This global analysis of the developing schistosome glycome provides new insights into how stage-specifically expressed glycans may contribute to different aspects of schistosome-host interactions.

Keywords

  • glycomics, glycosylation, host-pathogen interaction, mass spectrometry, parasite, glycan antigen, helminth, schistosome