title: The Role of Alveolar Epithelial Type II-Like Cells in Uptake of Structurally Different Antigens and in Polarisation of Local Immune Responses.
abstract: BACKGROUND
  Our previous studies on intranasal tolerance induction demonstrated reduction of allergic responses with different allergen constructs. The underlying mechanisms varied depending on their conformation or size.
  
  
  OBJECTIVE
  The aim of the present study was to compare the uptake of two structurally different allergen molecules within the respiratory tract following intranasal application.
  
  
  METHODS
  The three-dimensional Bet v 1 (Bv1-Protein) and the T cell epitope peptide of Bet v 1 (Bv1-Peptide) were labelled with 5,6-Carboxyfluorescein (FAM) and their uptake was investigated in lung cells and cells of the nasal associated lymphoid tissue from naive and sensitised BALB/c mice. Phenotypic characterisation of FAM+ lung cells after antigen incubation in vitro and after intranasal application was performed by flow cytometry. Impact of Bv1-Protein and Bv1-Peptide on cytokine profiles and gene expression in vivo or in an alveolar epithelial type II (ATII) cell line were assessed in mono- and co-cultures with monocytes using ELISA and quantitative real-time PCR.
  
  
  RESULTS
  Both antigens were taken up preferably by ATII-like cells (ATII-LCs) in naive mice, and by macrophages in sensitised mice. After intranasal application, Bv1-Peptide was taken up faster and more efficiently than Bv1-Protein. In vivo and in vitro experiments revealed that Bv1-Protein induced the transcription of thymic stromal lymphopoietin mRNA while Bv1-Peptide induced the transcription of IL-10 and MCP1 mRNA in ATII-LCs.
  
  
  CONCLUSIONS
  Both tested antigens were taken up by ATII-LCs under steady state conditions and induced different polarisation of the immune responses. These data may have an important impact for the generation of novel and more effective prophylactic or therapeutic tools targeting the respiratory mucosa.
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Johnnie
authors.initials: J
authors.lastname: Akgün
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Irma
authors.initials: I
authors.lastname: Schabussova
authors.affiliation: Laboratory of Gnotobiology, Institute of Microbiology, v.v.i., Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Schwarzer
authors.affiliation: Laboratory of Gnotobiology, Institute of Microbiology, v.v.i., Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Kozakova
authors.affiliation: Institute of Environmental Health, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.affiliation: Institute of Specific Prophylaxis and Tropical Medicine, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Göteborg, Göteborg, Sweden.
authors.forename: Ursula
authors.initials: U
authors.lastname: Wiedermann
mesh_terms: D000485:Allergens / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D052179:Antigens, Plant / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D000939:Epitopes / Q000737:chemistry; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D005452:Fluoresceins / Q000737:chemistry; D006967:Hypersensitivity; D007107:Immune System; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011650:Pulmonary Alveoli / Q000166:cytology*; D060888:Real-Time Polymerase Chain Reaction; D012137:Respiratory System / Q000276:immunology*
chemical_list: D000485:Allergens; D000941:Antigens; D052179:Antigens, Plant; D016207:Cytokines; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D005452:Fluoresceins; C061312:Bet v 1 allergen, Betula; C041126:5,6-dicarboxyfluorescein