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Effective treatment of allergic airway inflammation with Helicobacter pylori immunomodulators requires BATF3-dependent dendritic cells and IL-10.

  • Engler DB Institute of Molecular Cancer Research, University of Zürich, 8057 Zürich, Switzerland;
  • Reuter S Medical Clinic III and.
  • van Wijck Y Department of Pulmonology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;
  • Urban S Institute of Molecular Cancer Research, University of Zürich, 8057 Zürich, Switzerland;
  • Kyburz A Institute of Molecular Cancer Research, University of Zürich, 8057 Zürich, Switzerland;
  • Maxeiner J Medical Clinic III and.
  • Martin H Medical Clinic III and.
  • Yogev N Institute for Molecular Medicine, Johannes Gutenberg University, 55131 Mainz, Germany;
  • Waisman A Institute for Molecular Medicine, Johannes Gutenberg University, 55131 Mainz, Germany;
  • Gerhard M Institute of Microbiology, Immunology and Hygiene, Technical University of Munich and German Center for Infection Research, 81675 Munich, Germany; and.
  • Cover TL Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine and Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232-2358.
  • Taube C Department of Pulmonology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands;
  • Müller A Institute of Molecular Cancer Research, University of Zürich, 8057 Zürich, Switzerland; mueller@imcr.uzh.ch.
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  • 2014-07-31
Published in:
  • Proceedings of the National Academy of Sciences of the United States of America. - 2014
allergy and asthma prevention
bacterial immunomodulation
bacterial persistence determinants
tolerogenic dendritic cells
Allergens
Animals
Antigens, Bacterial
Asthma
Bacterial Proteins
Basic-Leucine Zipper Transcription Factors
Dendritic Cells
Disease Models, Animal
Helicobacter pylori
Humans
Immune Tolerance
Immunologic Factors
Interleukin-10
Interleukin-18
Mice
Mice, Inbred C57BL
Mice, Knockout
Repressor Proteins
T-Lymphocytes, Regulatory
gamma-Glutamyltransferase
English The prevalence of allergic asthma and other atopic diseases has reached epidemic proportions in large parts of the developed world. The gradual loss of the human indigenous microbiota has been held responsible for this trend. The bacterial pathogen Helicobacter pylori is a constituent of the normal gastric microbiota whose presence has been inversely linked to allergy and asthma in humans and experimental models. Here we show that oral or i.p. tolerization with H. pylori extract prevents the airway hyperresponsiveness, bronchoalveolar eosinophilia, pulmonary inflammation, and Th2 cytokine production that are hallmarks of allergen-induced asthma in mice. Asthma protection is not conferred by extracts from other enteropathogens and requires a heat-sensitive H. pylori component and the DC-intrinsic production of IL-10. The basic leucine zipper ATF-like 3 (BATF3)-dependent CD103(+)CD11b(-) dendritic cell lineage is enriched in the lungs of protected mice and strictly required for protection. Two H. pylori persistence determinants, the γ-glutamyl-transpeptidase GGT and the vacuolating cytotoxin VacA, are required and sufficient for asthma protection and can be administered in purified form to prevent asthma. In conclusion, we provide preclinical evidence for the concept that the immunomodulatory properties of H. pylori can be exploited for tolerization strategies aiming to prevent allergen-induced asthma.
Language
  • English
Open access status
bronze
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https://sonar.ch/global/documents/263398
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