title: Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion.
abstract: Mucins are heavily glycosylated proteins that give mucus its gel-like properties. Moreover, the glycans decorating the mucin protein core can alter the protective properties of the mucus barrier. To investigate whether these alterations could be parasite-induced we utilized the Trichuris muris (T. muris) infection model, using different infection doses and strains of mice that are resistant (high dose infection in BALB/c and C57BL6 mice) or susceptible (high dose infection in AKR and low dose infection in BALB/c mice) to chronic infection by T. muris. During chronicity, within the immediate vicinity of the T. muris helminth the goblet cell thecae contained mainly sialylated mucins. In contrast, the goblet cells within the epithelial crypts in the resistant models contained mainly sulphated mucins. Maintained mucin sulphation was promoted by TH2-immune responses, in particular IL-13, and contributed to the protective properties of the mucus layer, making it less vulnerable to degradation by T. muris excretory secretory products. Mucin sulphation was markedly reduced in the caecal goblet cells in the sulphate anion transporter-1 (Sat-1) deficient mice. We found that Sat-1 deficient mice were susceptible to chronic infection despite a strong TH2-immune response. Lower sulphation levels lead to decreased efficiency of establishment of T. muris infection, independent of egg hatching. This study highlights the complex process by which immune-regulated alterations in mucin glycosylation occur following T. muris infection, which contributes to clearance of parasitic infection.
authors.affiliation: Inflammatory Disease Biology and Therapeutics Group, Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Sumaira Z
authors.identifier: 0000-0001-8577-8628
authors.initials: SZ
authors.lastname: Hasnain
authors.affiliation: Inflammatory Disease Biology and Therapeutics Group, Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Dawson
authors.affiliation: Inflammatory Disease Biology and Therapeutics Group, Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Australia.|Mater Pathology Services, Mater Hospitals, South Brisbane, Queensland, Australia.
authors.forename: Rohan
authors.initials: R
authors.lastname: Lourie
authors.affiliation: Mater Pathology Services, Mater Hospitals, South Brisbane, Queensland, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Hutson
authors.affiliation: Inflammatory Disease Biology and Therapeutics Group, Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Tong
authors.affiliation: Manchester Immunology Group Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom.|Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Grencis
authors.affiliation: Inflammatory Disease Biology and Therapeutics Group, Mater Research Institute - The University of Queensland, Translational Research Institute, Brisbane, Australia.
authors.forename: Michael A
authors.identifier: 0000-0002-8375-2675
authors.initials: MA
authors.lastname: McGuckin
authors.affiliation: Manchester Immunology Group Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom.|Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: David J
authors.identifier: 0000-0001-7148-1970
authors.initials: DJ
authors.lastname: Thornton
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006031:Glycosylation; D020397:Goblet Cells / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009077:Mucins / Q000737:chemistry* / Q000276:immunology*; D016133:Polymerase Chain Reaction; D014257:Trichuriasis / Q000276:immunology*; D014258:Trichuris / Q000276:immunology
chemical_list: D009077:Mucins