title: Glycomic Analysis of Life Stages of the Human Parasite Schistosoma mansoni Reveals Developmental Expression Profiles of Functional and Antigenic Glycan Motifs.
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, whereas GalNAcβ1-4GlcNAc (LDN)-motifs gradually became abundant and predominated in adult worms. LeX-motifs were present on glycolipids up to 2 weeks of schistosomula development, whereas glycolipids with mono- and multifucosylated 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 multifucosylated 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 multifucosylated 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 subshell envelope in the developed egg. Lipid glycans with multifucosylated 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's glycome provides new insights into how stage-specifically expressed glycans may contribute to different aspects of schistosome-host interactions.
authors.affiliation: From the ‡Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Smit
authors.affiliation: From the ‡Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Angela
authors.initials: A
authors.lastname: van Diepen
authors.affiliation: From the ‡Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: D Linh
authors.initials: DL
authors.lastname: Nguyen
authors.affiliation: §Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
authors.affiliation: ¶Institute of Biological Environmental and Rural Sciences (IBERS), Aberystwyth University, Penglais Campus, Aberystwyth SY23 3FG, United Kingdom.
authors.forename: Karl F
authors.initials: KF
authors.lastname: Hoffmann
authors.affiliation: §Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
authors.affiliation: From the ‡Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; c.h.hokke@lumc.nl.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D000939:Epitopes / Q000378:metabolism; D054794:Glycomics / Q000379:methods*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008018:Life Cycle Stages; D008055:Lipids / Q000737:chemistry; D010063:Ovum / Q000378:metabolism; D010271:Parasites / Q000254:growth & development / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D012550:Schistosoma mansoni / Q000254:growth & development* / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; D006023:Glycoproteins; D008055:Lipids; D011134:Polysaccharides; D015800:Protozoan Proteins