Loading...
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
Kyburz, Andreas
Fallegger, Angela
Zhang, Xiaozhou
Altobelli, Aleksandra
Artola-Boran, Mariela
Borbet, Timothy
Urban, Sabine
Paul, Petra
Münz, Christian
Floess, Stefan
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2018-09-19
Submitted date
Files
Loading...
free HHS manuscript
Adobe PDF, 1.34 MB
Other Titles
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.
Citation
J Allergy Clin Immunol. 2019;143(4):1496-1512.e11. doi:10.1016/j.jaci.2018.07.046.
Publisher
PubMed ID
PubMed Central ID
PMC6592617
Additional Links
Embedded video
Type
Article
Other
Other
Language
en
Description
Series/Report no.
ISSN
EISSN
1097-6825
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 4.0 International