Involvement of the mannose receptor in the uptake of Der p 1, a major mite allergen, by human dendritic cells.
BACKGROUND
Immature dendritic cells (DCs) take up antigens in peripheral tissues and, after antigen processing, mature to efficiently stimulate T cells in secondary lymph nodes. In allergic airway diseases DCs have been shown to be involved in the induction and maintenance of a T(H)2-type profile.


OBJECTIVE
The present study was undertaken to determine pathways of Der p 1 (a house dust mite allergen) uptake by human DCs and to compare Der p 1 uptake between DCs from patients with house dust mite allergy and DCs from healthy donors.


METHODS
Monocyte-derived DCs (MD-DCs) were obtained from patients with house dust mite allergy (n = 13) and healthy donors (n = 11). Der p 1 was labeled with rhodamine. Der p 1 uptake by MD-DCs was analyzed by means of flow cytometry and confocal microscopy.


RESULTS
Rhodamine- labeled Der p 1 was demonstrated to be taken up by MD-DCs in a dose-, time-, and temperature- dependent manner. The involvement of the mannose receptor (MR) in the Der p 1 uptake was demonstrated by using (1) inhibitors of the MR- mediated endocytosis (mannan and blocking anti-MR mAb), which inhibited the Der p 1 uptake from 40 % to 50 %, and (2) confocal microscopy showing the colocalization of rhodamine-labeled Der p 1 with FITC-dextran. Interestingly, compared with DCs from healthy donors, DCs from allergic patients expressed more MR and were more efficient in Der p 1 uptake.


CONCLUSIONS
These results suggest that the MR could play a key role in the Der p 1 allergen uptake by DCs and in the pathogenesis of allergic diseases in dust mite -sensitive patients.
Deslée
Gaëtan
G
Unité INSERM U-416, Institut Pasteur de Lille, France.
Charbonnier
Anne-Sophie
AS
Hammad
Hamida
H
Angyalosi
Gerhild
G
Tillie-Leblond
Isabelle
I
Mantovani
Alberto
A
Tonnel
André-Bernard
AB
Pestel
Joël
J
D000328:Adult; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000378:metabolism*; D060829:Arthropod Proteins; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007700:Kinetics; D037181:Lectins, C-Type; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008875:Middle Aged; D008925:Mites / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology*; D013696:Temperature
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1