The major birch pollen allergen Bet v 1 induces different responses in dendritic cells of birch pollen allergic and healthy individuals

• Published in: PloS one Vol. 10; no. 1; p. e0117904
• Main Authors: Smole, Ursula, Radauer, Christian, Lengger, Nina, Svoboda, Martin, Rigby, Neil, Bublin, Merima, Gaier, Sonja, Hoffmann-Sommergruber, Karin, Jensen-Jarolim, Erika, Mechtcheriakova, Diana, Breiteneder, Heimo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.01.2015; Public Library of Science (PLoS)
• Subjects: Activation; Adult; Allergens; Allergens - immunology; Allergy; Antigens; Antigens, Plant - immunology; B cells; Bet v 1 antigen; Betula - immunology; Binding; Binding, Competitive; Case-Control Studies; Celery; Cell surface; Chemokines; Cross-Linking Reagents - metabolism; Crosslinking; Cytokines; Cytometry; Dendritic cells; Dendritic Cells - immunology; Endocytosis; Enzyme Activation; Ethics; Extracellular signal-regulated kinase; Female; Flow cytometry; Food allergies; Gene expression; Gene Expression Regulation; Genes; Humans; Hypersensitivity - genetics; Hypersensitivity - immunology; Immune response; Immune system; Immunofluorescence; Immunoglobulin E; Immunoglobulin E - immunology; Immunological tolerance; Immunology; Interleukin 13; Interleukin 4; Internalization; Intracellular signalling; Kinases; Kinetics; Lymphocytes T; Male; MAP kinase; Microscopy; Mitogen-Activated Protein Kinases - metabolism; Monocytes; Monocytes - cytology; NF-κB protein; Phosphorylation; Pollen; Pollen - immunology; Proteins; Reaction kinetics; Receptors, IgE - metabolism; Research parks; RNA; Rodents; T cell receptors; Th2 Cells - immunology; Transcription; Transcription, Genetic
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0117904

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.