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.
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.
Royer
Pierre-Joseph
PJ
School of Molecular Medical Sciences, University of Nottingham, Queen's Medical Centre, United Kingdom.
Emara
Mohamed
M
Yang
Chaoxing
C
Al-Ghouleh
Abeer
A
Tighe
Paddy
P
Jones
Nick
N
Sewell
Herb F
HF
Shakib
Farouk
F
Martinez-Pomares
Luisa
L
Ghaemmaghami
Amir M
AM
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
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