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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Allergens / metabolism
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Allergens / physiology*
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Animals
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Antigens, Dermatophagoides / immunology*
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Antigens, Dermatophagoides / metabolism
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Arthropod Proteins
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Cell Polarity / immunology*
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Coculture Techniques
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Cysteine Endopeptidases
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Dendritic Cells / enzymology*
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Female
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Humans
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Hypersensitivity / immunology
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Hypersensitivity / therapy
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Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis
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Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
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Lectins, C-Type / antagonists & inhibitors
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Lectins, C-Type / metabolism
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Lectins, C-Type / physiology*
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Male
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Mannose Receptor
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Mannose-Binding Lectins / antagonists & inhibitors
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Mannose-Binding Lectins / metabolism
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Mannose-Binding Lectins / physiology*
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Protein Binding / immunology
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Pyroglyphidae / immunology
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Pyroglyphidae / metabolism
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Receptors, Cell Surface / antagonists & inhibitors
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Receptors, Cell Surface / metabolism
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Receptors, Cell Surface / physiology*
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Th2 Cells / enzymology
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Th2 Cells / immunology*
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Up-Regulation / immunology
Substances
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Allergens
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Antigens, Dermatophagoides
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Arthropod Proteins
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Lectins, C-Type
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Mannose Receptor
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Mannose-Binding Lectins
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Receptors, Cell Surface
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Cysteine Endopeptidases
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Dermatophagoides pteronyssinus antigen p 1