title: The mannose receptor mediates the uptake of diverse native allergens by dendritic cells and determines allergen-induced T cell polarization through modulation of IDO activity.
abstract: The mannose receptor (MR) is a C-type lectin expressed by dendritic cells (DCs). We have investigated the ability of MR to recognize glycosylated allergens. Using a gene silencing strategy, we have specifically inhibited the expression of MR on human monocyte-derived DCs. We show that MR mediates internalization of diverse allergens from mite (Der p 1 and Der p 2), dog (Can f 1), cockroach (Bla g 2), and peanut (Ara h 1) through their carbohydrate moieties. All of these allergens bind to the C-type lectin-like carbohydrate recognition domains 4-7 of MR. We have also assessed the contribution of MR to T cell polarization after allergen exposure. We show that silencing MR expression on monocyte-derived DCs reverses the Th2 cell polarization bias, driven by Der p 1 allergen exposure, through upregulation of IDO activity. In conclusion, our work demonstrates a major role for MR in glycoallergen recognition and in the development of Th2 responses.
authors.affiliation: School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, United Kingdom.
authors.forename: Pierre-Joseph
authors.initials: PJ
authors.lastname: Royer
authors.forename: Mohamed
authors.initials: M
authors.lastname: Emara
authors.forename: Chaoxing
authors.initials: C
authors.lastname: Yang
authors.forename: Abeer
authors.initials: A
authors.lastname: Al-Ghouleh
authors.forename: Paddy
authors.initials: P
authors.lastname: Tighe
authors.forename: Nick
authors.initials: N
authors.lastname: Jones
authors.forename: Herb F
authors.initials: HF
authors.lastname: Sewell
authors.forename: Farouk
authors.initials: F
authors.lastname: Shakib
authors.forename: Luisa
authors.initials: L
authors.lastname: Martinez-Pomares
authors.forename: Amir M
authors.initials: AM
authors.lastname: Ghaemmaghami
mesh_terms: D000328:Adult; D000485:Allergens / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology* / Q000378:metabolism; D060829:Arthropod Proteins; D016764:Cell Polarity / Q000276:immunology*; D018920:Coculture Techniques; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000378:metabolism*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1