title: Glycans of Schistosoma mansoni and keyhole limpet haemocyanin induce hepatic granulomas in vivo.
abstract: Schistosoma mansoni eggs trapped in the liver of an infected host cause the major pathological manifestations of schistosomiasis. Miracidia within the deposited eggs secrete soluble egg antigens (SEA) that induce periovular granuloma formation, which may lead to severe hepatic fibrosis. Several reports have highlighted the immunomodulatory capacities of carbohydrate determinants present in the glycoproteins of SEA. These glycans contain among others the immunogenic Galbeta1-4(Fucalpha1-3)GlcNAc (LewisX) and GalNAcbeta1-4(Fucalpha1-2Fucalpha1-3)GlcNAc (LDN-DF) elements. Due to cross-reactivity with schistosomal glycan antigens, keyhole limpet haemocyanin (KLH) has been used extensively for diagnostic and therapeutic studies on schistosomiasis. In the present study, a granulomatous response with numerous eosinophils towards SEA- and KLH-coated beads implanted in the liver by mesenteric injection was observed. Immunophenotyping of these experimentally induced granulomas for cellular recruitment, chemokines, adhesion and extracellular matrix proteins revealed very close resemblance with hepatic lesions evoked by native schistosome eggs, hence demonstrating the usefulness of the bead model, in general, as well as of KLH as a model antigen to study the immunopathological mechanisms of schistosome infections. While trypsin digestion of KLH did not alter its antigenic characteristics, beads coated with SEA or KLH treated with sodium periodate to destroy the immunological properties of their carbohydrate chains, yielded only a monolayer of macrophages similar to negative control beads. Up-regulation of ICAM-1, LFA-1 and fibronectin in SEA-induced granulomas and in native and trypsinised KLH-induced granulomas indicates a major role of the carbohydrate elements of SEA and KLH in the initiation and homeostasis of the inflammatory response. These data provide new insights in the complex and multifactorial carbohydrate-dependent host-parasite immunological interactions.
authors.affiliation: Department of Pathology, University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.
authors.forename: Koen K
authors.initials: KK
authors.lastname: van de Vijver
authors.forename: Cornelis H
authors.initials: CH
authors.lastname: Hokke
authors.forename: Alexandra
authors.initials: A
authors.lastname: van Remoortere
authors.forename: Werner
authors.initials: W
authors.lastname: Jacobs
authors.forename: André M
authors.initials: AM
authors.lastname: Deelder
authors.forename: Eric A
authors.initials: EA
authors.lastname: Van Marck
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006099:Granuloma / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology*; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008109:Liver Diseases, Parasitic / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010270:Parasite Egg Count; D011134:Polysaccharides / Q000032:analysis / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D012995:Solubility; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D000947:Antigens, Helminth; D005353:Fibronectins; D006023:Glycoproteins; D016169:Lymphocyte Function-Associated Antigen-1; D011134:Polysaccharides; D018799:Intercellular Adhesion Molecule-1; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin