title: Fasciola hepatica Surface Tegument: Glycoproteins at the Interface of Parasite and Host.
abstract: Fasciola hepatica, commonly known as liver fluke, is a trematode that causes Fasciolosis in ruminants and humans. The outer tegumental coat of F. hepatica (FhTeg) is a complex metabolically active biological matrix that is continually exposed to the host immune system and therefore makes a good vaccine target. F. hepatica tegumental coat is highly glycosylated and helminth-derived immunogenic oligosaccharide motifs and glycoproteins are currently being investigated as novel vaccine candidates. This report presents the first systematic characterization of FhTeg glycosylation using lectin microarrays to characterize carbohydrates motifs present, and lectin histochemistry to localize these on the F. hepatica tegument. We discovered that FhTeg glycoproteins are predominantly oligomannose oligosaccharides that are expressed on the spines, suckers and tegumental coat of F. hepatica and lectin blot analysis confirmed the abundance of N- glycosylated proteins. Although some oligosaccharides are widely distributed on the fluke surface other subsets are restricted to distinct anatomical regions. We selectively enriched for FhTeg mannosylated glycoprotein subsets using lectin affinity chromatography and identified 369 proteins by mass spectrometric analysis. Among these proteins are a number of potential vaccine candidates with known immune modulatory properties including proteases, protease inhibitors, paramyosin, Venom Allergen-like II, Enolase and two proteins, nardilysin and TRIL, that have not been previously associated with F. hepatica Furthermore, we provide a comprehensive insight regarding the putative glycosylation of FhTeg components that could highlight the importance of further studies examining glycoconjugates in host-parasite interactions in the context of F. hepatica infection and the development of an effective vaccine.
authors.affiliation: From the ‡Fundamental and Translational Immunology, School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin, Dublin 9, Ireland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ravidà
authors.affiliation: §School of Biological Sciences, Medical Biology Centre (MBC), Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Cwiklinski
authors.affiliation: From the ‡Fundamental and Translational Immunology, School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin, Dublin 9, Ireland.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Aldridge
authors.affiliation: ¶Glycoselect, Dublin City University, Glasnevin, Dublin 9.
authors.forename: Paul
authors.initials: P
authors.lastname: Clarke
authors.affiliation: ¶Glycoselect, Dublin City University, Glasnevin, Dublin 9.
authors.forename: Roisin
authors.initials: R
authors.lastname: Thompson
authors.affiliation: ‖Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland Galway, Ireland; **Regenerative Medicine Institute, NUI Galway, Ireland.
authors.forename: Jared Q
authors.initials: JQ
authors.lastname: Gerlach
authors.affiliation: ‖Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland Galway, Ireland; ‡‡Carbohydrate Signalling Group, Microbiology, NUI Galway, Ireland.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kilcoyne
authors.affiliation: §§Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
authors.affiliation: §School of Biological Sciences, Medical Biology Centre (MBC), Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Dalton
authors.affiliation: From the ‡Fundamental and Translational Immunology, School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin, Dublin 9, Ireland; Sandra.ONeill@dcu.ie.
authors.forename: Sandra M
authors.initials: SM
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D005210:Fasciola hepatica / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D015801:Helminth Proteins / Q000378:metabolism; D006790:Host-Parasite Interactions; D037102:Lectins / Q000378:metabolism; D013058:Mass Spectrometry; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics
chemical_list: D006023:Glycoproteins; D015801:Helminth Proteins; D037102:Lectins