title: BCG priming of dendritic cells enhances T regulatory and Th1 function and suppresses allergen-induced Th2 function in vitro and in vivo.
abstract: BACKGROUND
  The inverse correlation of mycobacterial infection with asthma prevalence and the inhibitory effects of vaccination with Bacille Calmette-Guérin (BCG) on airway hyperreactivity in asthma models suggest modulation of dendritic cell (DC) and T cell functions by mycobacterial compounds.
  
  
  METHODS
  To delineate these immunological effects, the immunogenicity of BCG Copenhagen, BCG Chicago and BCG Pasteur was compared in a mouse model. Bone marrow-derived dendritic cells (BMDCs) from BALB/c mice were stimulated with ovalbumin (OVA) with or without BCG. BMDCs were phenotypically characterized by flow cytometry, and we used ELISA to measure the cytokine production of BMDCs as well as of co-cultivated allergen-specific T cells in response to OVA-pulsed. Immunomodulatory effects of BCG were studied in a model of allergic airway inflammation by adoptive transfer of allergen-pulsed BMDCs.
  
  
  RESULTS
  Immunomodulation with BCG induced production of IL-10 and IL-12 by BMDCs. Co-cultured allergen-specific T cells produced less IL-5, IL-13 and IFN-gamma but more IL-10. Also the number of FoxP3(+) regulatory T cells was enhanced. Strongest effects were seen with BCG Chicago and BCG Pasteur. In vivo, administration of BCG modulated OVA-pulsed BMDCs then reduced eosinophilic airway inflammation but enhanced infiltration with granulocytes. Airway hyperreactivity and mucus production were reduced and more FoxP3(+) T cells were observed.
  
  
  CONCLUSIONS
  BCG-induced suppression of Th2-type allergic airway inflammation was associated with enhancement of regulatory T cell function but also of Th1-associated neutrophilic airway inflammation. These findings raise concerns regarding the safety profile of BCG as a potential tool for prevention and therapy of allergic airway disease.
authors.affiliation: Department of Paediatric Pneumology and Immunology, Charité Universitatsmedizin Berlin, Berlin, Germany. birgit.ahrens@charite.de
authors.forename: B
authors.initials: B
authors.lastname: Ahrens
authors.forename: C
authors.initials: C
authors.lastname: Gruber
authors.forename: R-D
authors.initials: RD
authors.lastname: Rha
authors.forename: T
authors.initials: T
authors.lastname: Freund
authors.forename: D
authors.initials: D
authors.lastname: Quarcoo
authors.forename: A
authors.initials: A
authors.lastname: Awagyan
authors.forename: A
authors.initials: A
authors.lastname: Hutloff
authors.forename: A M
authors.initials: AM
authors.lastname: Dittrich
authors.forename: U
authors.initials: U
authors.lastname: Wahn
authors.forename: E
authors.initials: E
authors.lastname: Hamelmann
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001500:BCG Vaccine / Q000494:pharmacology / Q000592:standards / Q000627:therapeutic use*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000188:drug therapy*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control
chemical_list: D000485:Allergens; D001500:BCG Vaccine; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin