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

Daniela B. Engler; Sebastian Reuter; Yolanda van WijckSabine UrbanAndreas KyburzJoachim MaxeinerHelen MartinNir YogevAri WaismanMarkus GerhardTimothy L. CoverChristian TaubeAnne Müller

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

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

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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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第32期|11810-11815|共6页
作者
Daniela B. Engler; Sebastian Reuter; Yolanda van WijckSabine UrbanAndreas KyburzJoachim MaxeinerHelen MartinNir YogevAri WaismanMarkus GerhardTimothy L. CoverChristian TaubeAnne Müller;
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作者单位

Institute of Molecular Cancer Research, University of Zürich, 8057 Zürich, Switzerland;

Medical Clinic III, Johannes Gutenberg University, 55131 Mainz, Germany;

Department of Pulmonology, Leiden University Medical Center, 2333 ZA, Leiden, The NetherlandsInstitute for Molecular Medicine, Johannes Gutenberg University, 55131 Mainz, GermanyInstitute of Microbiology, Immunology and Hygiene, Technical University of Munich and German Center for Infection Research, 81675 Munich, GermanyDivision of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine and Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232-2358;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
bacterial immunomodulation; allergy and asthma prevention; tolerogenic dendritic cells; bacterial persistence determinants;

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

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