title: The Human Glycoprotein Salivary Agglutinin Inhibits the Interaction of DC-SIGN and Langerin with Oral Micro-Organisms.
abstract: Salivary agglutinin (SAG), also known as gp340 or SALSA, is a glycoprotein encoded by the Deleted in Malignant Brain Tumours 1 gene and is abundantly present in human saliva. SAG aggregates bacteria and viruses, thereby promoting their clearance from the oral cavity. The mucosa lining the oral cavity contains dendritic cells (DC) and Langerhans cells (LC), which express the C-type lectin receptors (CLR) DC-SIGN and Langerin, respectively. Both DC-SIGN and Langerin recognise mannose and fucose carbohydrate structures on pathogens and self-glycoproteins to regulate immunity and homeostasis. The purpose of this study was to investigate whether SAG interacts with these CLR and whether this interferes with the binding to oral pathogens. We show that whole parotid saliva and SAG, when coated to microplates, strongly interact with DC-SIGN and Langerin, probably via mannose and fucose structures. Also, primary human DC and LC bind parotid saliva and SAG via DC-SIGN and Langerin, respectively. Furthermore, SAG binding to DC-SIGN or Langerin prevented binding to the micro-organisms Candida albicans and Escherichia coli which express mannose and fucose-containing glycan structures. Thus, binding of saliva glycoprotein SAG to DC-SIGN and Langerin may inhibit pathogen-DC/LC interactions, and could prove to be a new immunomodulatory mechanism of SAG.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center (VUmc), Amsterdam, The Netherlands.
authors.forename: Martine A
authors.initials: MA
authors.lastname: Boks
authors.forename: Sabrina T G
authors.initials: ST
authors.lastname: Gunput
authors.forename: Ilona
authors.initials: I
authors.lastname: Kosten
authors.forename: Susan
authors.initials: S
authors.lastname: Gibbs
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: Ligtenberg
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001422:Bacterial Adhesion; D002135:Calcium-Binding Proteins; D002176:Candida albicans / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000378:metabolism; D009061:Mouth Mucosa / Q000276:immunology*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology*; D025521:Tumor Suppressor Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C121916:CD207 protein, human; C108174:DMBT1 protein, human