Mycobacterium bovis Bacillus Calmette-Guérin Killed by Extended Freeze-Drying Targets Plasmacytoid Dendritic Cells To Regulate Lung Inflammation
| Autor: | Micheline Lagranderie, Mohammad Abolhassani, Gilles Marchal, Carla Lima, A.-M. Balazuc, Jeroen Vanoirbeek, B. Boris Vargaftig |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Ovalbumin T cell Immunology Peroxisome proliferator-activated receptor Mice Inbred Strains Inflammation Spleen Biology T-Lymphocytes Regulatory complex mixtures Allergic inflammation Mice Downregulation and upregulation RAR-related orphan receptor gamma medicine Animals Immunology and Allergy Lung chemistry.chemical_classification hemic and immune systems Dendritic Cells Pneumonia Mycobacterium bovis PPAR gamma Freeze Drying Treatment Outcome medicine.anatomical_structure chemistry BCG Vaccine medicine.symptom BCG vaccine Transcription Factors |
| Zdroj: | The Journal of Immunology. 184:1062-1070 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | We have previously shown that bacillus Calmette-Guérin (BCG) inactivated by extended freeze-drying (EFD) reduces airway hyperresponsiveness, whereas live and heat-killed BCG fail to do so. However, the cells involved in the protective effect and the signaling and transcriptional networks that could reprogram T cell commitment after EFD BCG treatment remained to be elucidated. We investigated whether EFD BCG targets plasmacytoid dendritic cells (pDCs) potentially involved in the polarization of regulatory T cells (Tregs) and the transcriptional factors that regulate allergic inflammation. OVA-sensitized mice were s.c. injected with EFD, live, or heat-killed BCG. We analyzed after the injection of the various BCG preparations: 1) pDCs recruited in the draining lymph nodes (day 4); 2) transcription factors involved in inflammation and T cell commitment in spleen and lungs after OVA challenge (day 28). Airway hyperresponsiveness and transcription factors were determined after in vivo depletion of pDCs or Tregs in EFD BCG-treated and OVA-challenged mice. EFD BCG reduced inflammation via the recruitment of pDCs polarizing the differentiation of naive CD4+ T lymphocytes into Tregs. In vivo, pDC or Treg depletion at the time of EFD BCG treatment abrogated the protection against inflammation. EFD BCG treatment upregulated Forkhead-winged helix transcription factor (Treg signature) and downregulated GATA-3 and RORγt (Th2 and Th17 signatures) more efficiently than live and heat-killed BCG. Moreover, only EFD BCG enhanced peroxisome proliferator-activated receptor γ expression and blocked NF-κB activation, cyclooxygenase expression, and p38 MAPK phosphorylation. EFD BCG reduced allergic inflammation by recruiting pDCs that promoted Tregs; EFD BCG acted as a peroxisome proliferator-activated receptor γ agonist and thus could be used in asthma and other inflammatory diseases. |
| Databáze: | OpenAIRE |
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