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Treatment with Helicobacter pylori-derived VacA attenuates allergic airway disease

BACKGROUND: Asthma is an incurable heterogeneous disease with variations in clinical and underlying immunological phenotype. New approaches could help to support existing therapy concepts. Neonatal infection of mice with Helicobacter pylori or administration of H. pylori-derived extracts or molecule...

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Autores principales: Reuter, Sebastian, Raspe, Jonas, Uebner, Hendrik, Contoyannis, Alexandros, Pastille, Eva, Westendorf, Astrid M., Caso, Georgia C., Cover, Timothy L., Müller, Anne, Taube, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902502/
https://www.ncbi.nlm.nih.gov/pubmed/36761723
http://dx.doi.org/10.3389/fimmu.2023.1092801
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author Reuter, Sebastian
Raspe, Jonas
Uebner, Hendrik
Contoyannis, Alexandros
Pastille, Eva
Westendorf, Astrid M.
Caso, Georgia C.
Cover, Timothy L.
Müller, Anne
Taube, Christian
author_facet Reuter, Sebastian
Raspe, Jonas
Uebner, Hendrik
Contoyannis, Alexandros
Pastille, Eva
Westendorf, Astrid M.
Caso, Georgia C.
Cover, Timothy L.
Müller, Anne
Taube, Christian
author_sort Reuter, Sebastian
collection PubMed
description BACKGROUND: Asthma is an incurable heterogeneous disease with variations in clinical and underlying immunological phenotype. New approaches could help to support existing therapy concepts. Neonatal infection of mice with Helicobacter pylori or administration of H. pylori-derived extracts or molecules after birth have been shown to prevent the development of allergic airway disease later in life. This study evaluated the potential therapeutic efficacy of H. pylori vacuolating cytotoxin A (VacA) in allergic airway inflammation and investigated the underlying immunological mechanisms for its actions. METHODS: Murine models of allergic airway diseases, and murine and human in vitro models were used. RESULTS: In both an acute model and a therapeutic house dust mite model of allergic airway disease, treatment with H. pylori-derived VacA reduced several asthma hallmarks, including airway hyperresponsiveness, inflammation and goblet cell metaplasia. Flow cytometry and ELISA analyses revealed induction of tolerogenic dendritic cells (DC) and FoxP3 positive regulatory T cells (Tregs), and a shift in the composition of allergen-specific immunoglobulins. Depletion of Tregs during treatment with VacA reversed treatment-mediated suppression of allergic airway disease. Human monocyte derived DCs (moDC) that were exposed to VacA induced Tregs in co-cultured naïve autologous T cells, replicating key observations made in vivo. CONCLUSION: H. pylori-derived VacA suppressed allergic airway inflammation via induction of Tregs in both allergic airway disease models. These data suggest that the immunomodulatory activity of VacA could potentially be exploited for the prevention and treatment of allergic airway disease.
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spelling pubmed-99025022023-02-08 Treatment with Helicobacter pylori-derived VacA attenuates allergic airway disease Reuter, Sebastian Raspe, Jonas Uebner, Hendrik Contoyannis, Alexandros Pastille, Eva Westendorf, Astrid M. Caso, Georgia C. Cover, Timothy L. Müller, Anne Taube, Christian Front Immunol Immunology BACKGROUND: Asthma is an incurable heterogeneous disease with variations in clinical and underlying immunological phenotype. New approaches could help to support existing therapy concepts. Neonatal infection of mice with Helicobacter pylori or administration of H. pylori-derived extracts or molecules after birth have been shown to prevent the development of allergic airway disease later in life. This study evaluated the potential therapeutic efficacy of H. pylori vacuolating cytotoxin A (VacA) in allergic airway inflammation and investigated the underlying immunological mechanisms for its actions. METHODS: Murine models of allergic airway diseases, and murine and human in vitro models were used. RESULTS: In both an acute model and a therapeutic house dust mite model of allergic airway disease, treatment with H. pylori-derived VacA reduced several asthma hallmarks, including airway hyperresponsiveness, inflammation and goblet cell metaplasia. Flow cytometry and ELISA analyses revealed induction of tolerogenic dendritic cells (DC) and FoxP3 positive regulatory T cells (Tregs), and a shift in the composition of allergen-specific immunoglobulins. Depletion of Tregs during treatment with VacA reversed treatment-mediated suppression of allergic airway disease. Human monocyte derived DCs (moDC) that were exposed to VacA induced Tregs in co-cultured naïve autologous T cells, replicating key observations made in vivo. CONCLUSION: H. pylori-derived VacA suppressed allergic airway inflammation via induction of Tregs in both allergic airway disease models. These data suggest that the immunomodulatory activity of VacA could potentially be exploited for the prevention and treatment of allergic airway disease. Frontiers Media S.A. 2023-01-24 /pmc/articles/PMC9902502/ /pubmed/36761723 http://dx.doi.org/10.3389/fimmu.2023.1092801 Text en Copyright © 2023 Reuter, Raspe, Uebner, Contoyannis, Pastille, Westendorf, Caso, Cover, Müller and Taube https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Reuter, Sebastian
Raspe, Jonas
Uebner, Hendrik
Contoyannis, Alexandros
Pastille, Eva
Westendorf, Astrid M.
Caso, Georgia C.
Cover, Timothy L.
Müller, Anne
Taube, Christian
Treatment with Helicobacter pylori-derived VacA attenuates allergic airway disease
title Treatment with Helicobacter pylori-derived VacA attenuates allergic airway disease
title_full Treatment with Helicobacter pylori-derived VacA attenuates allergic airway disease
title_fullStr Treatment with Helicobacter pylori-derived VacA attenuates allergic airway disease
title_full_unstemmed Treatment with Helicobacter pylori-derived VacA attenuates allergic airway disease
title_short Treatment with Helicobacter pylori-derived VacA attenuates allergic airway disease
title_sort treatment with helicobacter pylori-derived vaca attenuates allergic airway disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9902502/
https://www.ncbi.nlm.nih.gov/pubmed/36761723
http://dx.doi.org/10.3389/fimmu.2023.1092801
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