Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells

Andreas Kyburz, Angela Fallegger, Xiaozhou Zhang, Aleksandra Altobelli, Mariela Artola-Boran, Timothy Borbet, Sabine Urban, Petra Paul, Christian Münz, Stefan Floess, Jochen Huehn, Timothy L. Cover, Martin Blaser, Christian Taube, Anne Müller

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Transmaternal exposure to tobacco, microbes, nutrients, and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand and is inversely associated with allergies and chronic inflammatory conditions on the other. Objective: Here we investigate the consequences of transmaternal exposure to H pylori in utero and/or during lactation for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and development of immune cell populations in the lungs and lymphoid organs. Methods: We use experimental models of house dust mite– or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter rodentium infection along with metagenomics analyses, multicolor flow cytometry, and bisulfite pyrosequencing, to study the effects of H pylori on allergy severity and immunologic and microbiome correlates thereof. Results: Perinatal exposure to H pylori extract or its immunomodulator vacuolating cytotoxin confers robust protective effects against allergic airway inflammation not only in first- but also second-generation offspring but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T cells, expansion of regulatory T-cell subsets expressing CXCR3 or retinoic acid–related orphan receptor γt, and demethylation of the forkhead box P3 (FOXP3) locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H pylori exposure. Conclusion: We conclude that exposure to H pylori has consequences not only for the carrier but also for subsequent generations that can be exploited for interventional purposes.

Original languageEnglish (US)
Pages (from-to)1496-1512.e11
JournalJournal of Allergy and Clinical Immunology
Volume143
Issue number4
DOIs
StatePublished - Apr 1 2019
Externally publishedYes

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Pylorus
Regulatory T-Lymphocytes
Helicobacter pylori
Inflammation
Hypersensitivity
Microbiota
Virus Diseases
Bacterial Infections
Stomach
Citrobacter rodentium
Genetic Epigenesis
Metagenomics
Pyroglyphidae
Influenza A virus
Cytotoxins
Ovalbumin
Immunologic Factors
T-Lymphocyte Subsets
Lactation
Tobacco

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Kyburz, Andreas ; Fallegger, Angela ; Zhang, Xiaozhou ; Altobelli, Aleksandra ; Artola-Boran, Mariela ; Borbet, Timothy ; Urban, Sabine ; Paul, Petra ; Münz, Christian ; Floess, Stefan ; Huehn, Jochen ; Cover, Timothy L. ; Blaser, Martin ; Taube, Christian ; Müller, Anne. / Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells. In: Journal of Allergy and Clinical Immunology. 2019 ; Vol. 143, No. 4. pp. 1496-1512.e11.
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title = "Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells",
abstract = "Background: Transmaternal exposure to tobacco, microbes, nutrients, and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand and is inversely associated with allergies and chronic inflammatory conditions on the other. Objective: Here we investigate the consequences of transmaternal exposure to H pylori in utero and/or during lactation for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and development of immune cell populations in the lungs and lymphoid organs. Methods: We use experimental models of house dust mite– or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter rodentium infection along with metagenomics analyses, multicolor flow cytometry, and bisulfite pyrosequencing, to study the effects of H pylori on allergy severity and immunologic and microbiome correlates thereof. Results: Perinatal exposure to H pylori extract or its immunomodulator vacuolating cytotoxin confers robust protective effects against allergic airway inflammation not only in first- but also second-generation offspring but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T cells, expansion of regulatory T-cell subsets expressing CXCR3 or retinoic acid–related orphan receptor γt, and demethylation of the forkhead box P3 (FOXP3) locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H pylori exposure. Conclusion: We conclude that exposure to H pylori has consequences not only for the carrier but also for subsequent generations that can be exploited for interventional purposes.",
author = "Andreas Kyburz and Angela Fallegger and Xiaozhou Zhang and Aleksandra Altobelli and Mariela Artola-Boran and Timothy Borbet and Sabine Urban and Petra Paul and Christian M{\"u}nz and Stefan Floess and Jochen Huehn and Cover, {Timothy L.} and Martin Blaser and Christian Taube and Anne M{\"u}ller",
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Kyburz, A, Fallegger, A, Zhang, X, Altobelli, A, Artola-Boran, M, Borbet, T, Urban, S, Paul, P, Münz, C, Floess, S, Huehn, J, Cover, TL, Blaser, M, Taube, C & Müller, A 2019, 'Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells', Journal of Allergy and Clinical Immunology, vol. 143, no. 4, pp. 1496-1512.e11. https://doi.org/10.1016/j.jaci.2018.07.046

Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells. / Kyburz, Andreas; Fallegger, Angela; Zhang, Xiaozhou; Altobelli, Aleksandra; Artola-Boran, Mariela; Borbet, Timothy; Urban, Sabine; Paul, Petra; Münz, Christian; Floess, Stefan; Huehn, Jochen; Cover, Timothy L.; Blaser, Martin; Taube, Christian; Müller, Anne.

In: Journal of Allergy and Clinical Immunology, Vol. 143, No. 4, 01.04.2019, p. 1496-1512.e11.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells

AU - Kyburz, Andreas

AU - Fallegger, Angela

AU - Zhang, Xiaozhou

AU - Altobelli, Aleksandra

AU - Artola-Boran, Mariela

AU - Borbet, Timothy

AU - Urban, Sabine

AU - Paul, Petra

AU - Münz, Christian

AU - Floess, Stefan

AU - Huehn, Jochen

AU - Cover, Timothy L.

AU - Blaser, Martin

AU - Taube, Christian

AU - Müller, Anne

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Background: Transmaternal exposure to tobacco, microbes, nutrients, and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand and is inversely associated with allergies and chronic inflammatory conditions on the other. Objective: Here we investigate the consequences of transmaternal exposure to H pylori in utero and/or during lactation for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and development of immune cell populations in the lungs and lymphoid organs. Methods: We use experimental models of house dust mite– or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter rodentium infection along with metagenomics analyses, multicolor flow cytometry, and bisulfite pyrosequencing, to study the effects of H pylori on allergy severity and immunologic and microbiome correlates thereof. Results: Perinatal exposure to H pylori extract or its immunomodulator vacuolating cytotoxin confers robust protective effects against allergic airway inflammation not only in first- but also second-generation offspring but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T cells, expansion of regulatory T-cell subsets expressing CXCR3 or retinoic acid–related orphan receptor γt, and demethylation of the forkhead box P3 (FOXP3) locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H pylori exposure. Conclusion: We conclude that exposure to H pylori has consequences not only for the carrier but also for subsequent generations that can be exploited for interventional purposes.

AB - Background: Transmaternal exposure to tobacco, microbes, nutrients, and other environmental factors shapes the fetal immune system through epigenetic processes. The gastric microbe Helicobacter pylori represents an ancestral constituent of the human microbiota that causes gastric disorders on the one hand and is inversely associated with allergies and chronic inflammatory conditions on the other. Objective: Here we investigate the consequences of transmaternal exposure to H pylori in utero and/or during lactation for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and development of immune cell populations in the lungs and lymphoid organs. Methods: We use experimental models of house dust mite– or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter rodentium infection along with metagenomics analyses, multicolor flow cytometry, and bisulfite pyrosequencing, to study the effects of H pylori on allergy severity and immunologic and microbiome correlates thereof. Results: Perinatal exposure to H pylori extract or its immunomodulator vacuolating cytotoxin confers robust protective effects against allergic airway inflammation not only in first- but also second-generation offspring but does not increase susceptibility to viral or bacterial infection. Immune correlates of allergy protection include skewing of regulatory over effector T cells, expansion of regulatory T-cell subsets expressing CXCR3 or retinoic acid–related orphan receptor γt, and demethylation of the forkhead box P3 (FOXP3) locus. The composition and diversity of the gastrointestinal microbiota is measurably affected by perinatal H pylori exposure. Conclusion: We conclude that exposure to H pylori has consequences not only for the carrier but also for subsequent generations that can be exploited for interventional purposes.

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