title: The major birch pollen allergen Bet v 1 induces different responses in dendritic cells of birch pollen allergic and healthy individuals.
abstract: Dendritic cells play a fundamental role in shaping the immune response to allergens. The events that lead to allergic sensitization or tolerance induction during the interaction of the major birch pollen allergen Bet v 1 and dendritic cells are not very well studied. Here, we analyzed the uptake of Bet v 1 and the cross-reactive celery allergen Api g 1 by immature monocyte-derived dendritic cells (iMoDCs) of allergic and normal donors. In addition, we characterized the allergen-triggered intracellular signaling and transcriptional events. Uptake kinetics, competitive binding, and internalization pathways of labeled allergens by iMoDCs were visualized by live-cell imaging. Surface-bound IgE was detected by immunofluorescence microscopy and flow cytometry. Allergen- and IgE-induced gene expression of early growth response genes and Th1 and Th2 related cytokines and chemokines were analyzed by real-time PCR. Phosporylation of signaling kinases was analyzed by Western blot. Internalization of Bet v 1 by iMoDCs of both donor groups, likely by receptor-mediated caveolar endocytosis, followed similar kinetics. Bet v 1 outcompeted Api g 1 in cell surface binding and uptake. MoDCs of allergic and healthy donors displayed surface-bound IgE and showed a pronounced upregulation of Th2 cytokine- and NFκB-dependent genes upon non-specific Fcε receptor cross-linking. In contrast to these IgE-mediated responses, Bet v 1-stimulation increased transcript levels of the Th2 cytokines IL-4 and IL-13 but not of NFκB-related genes in MoDCs of BP allergic donors. Cells of healthy donors were either unresponsive or showed elevated mRNA levels of Th1-promoting chemokines. Moreover, Bet v 1 was able to induce Erk1/2 and p38 MAPK activation in BP allergics but only a slight p38 activation in normal donors. In conclusion, our data indicate that Bet v 1 favors the activation of a Th2 program only in DCs of BP allergic individuals.
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria; Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors: Ursula
authors: U
authors: Smole
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Christian
authors: C
authors: Radauer
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Nina
authors: N
authors: Lengger
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Martin
authors: M
authors: Svoboda
authors: Institute of Food Research, Norwich Research Park, Norwich, United Kingdom.
authors: Neil
authors: N
authors: Rigby
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Merima
authors: M
authors: Bublin
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Sonja
authors: S
authors: Gaier
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Karin
authors: K
authors: Hoffmann-Sommergruber
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria; Messerli Research Institute of the Medical University of Vienna, Veterinary University of Vienna and University of Vienna, Austria.
authors: Erika
authors: E
authors: Jensen-Jarolim
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Diana
authors: D
authors: Mechtcheriakova
authors: Department of Pathophysiology and Allergy Research; Center for Pathophysiology, Infectiology, and Immunology, Medical University of Vienna, Vienna, Austria.
authors: Heimo
authors: H
authors: Breiteneder
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology*; D029662:Betula / Q000276:immunology*; D001667:Binding, Competitive; D016022:Case-Control Studies; D003432:Cross-Linking Reagents / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D004789:Enzyme Activation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007700:Kinetics; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D010766:Phosphorylation; D011058:Pollen / Q000276:immunology*; D017455:Receptors, IgE / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D003432:Cross-Linking Reagents; D017455:Receptors, IgE; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E; D020928:Mitogen-Activated Protein Kinases
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