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J Allergy Clin Immunol. 2019 Apr;143(4):1496-1512.e11. doi: 10.1016/j.jaci.2018.07.046. Epub 2018 Sep 19.

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

Author information

1
Institute of Molecular Cancer Research, University of Zürich, Zurich, Switzerland.
2
Human Microbiome Program, New York University Langone Medical Center, New York, NY.
3
Institute of Experimental Immunology, University of Zürich, Zurich, Switzerland.
4
Department Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
5
Vanderbilt University Medical Center and Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tenn.
6
Department of Pulmonary Medicine, University Hospital Essen-Ruhrlandklinik, Essen, Germany.
7
Institute of Molecular Cancer Research, University of Zürich, Zurich, Switzerland. Electronic address: mueller@imcr.uzh.ch.

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.

KEYWORDS:

Allergic airway inflammation; epigenetic regulation of allergy and asthma; immune regulation; immune tolerance; metagenomics; microbial interventions during pregnancy

PMID:
30240703
PMCID:
PMC6592617
[Available on 2020-04-01]
DOI:
10.1016/j.jaci.2018.07.046

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