Trans-maternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T-cells

Publication date: Available online 19 September 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): 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 J. Blaser, Christian Taube, Anne Müller

Abstract

Background

The trans-maternal 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 trans-maternal exposure to H. pylori, in utero and/or during lactation, for susceptibility to viral and bacterial infection, predisposition to allergic airway inflammation, and the development of immune cell populations in the lung and lymphoid organs.

Methods

We use experimental models of house dust mite- or ovalbumin-induced airway inflammation and influenza A virus or Citrobacter infection along with metagenomics analyses, multi-color flow cytometry and bilsufite pyrosequencing to study the effects of H. pylori on allergy severity and immunological and microbiome correlates thereof.

Results

Perinatal exposure to H. pylori extract, or its immunomodulator VacA, confers robust protective effects against allergic airway inflammation not only in the first, but also the second offspring generation, 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 Treg subsets expressing CXCR3 or RORγt, and demethylation of the 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 may be exploited for interventional purposes.

Graphical abstract

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