Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells

J Clin Invest. 2011 Aug;121(8):3088-93. doi: 10.1172/JCI45041.

Abstract

Atopic asthma is a chronic disease of the airways that has taken on epidemic proportions in the industrialized world. The increase in asthma rates has been linked epidemiologically to the rapid disappearance of Helicobacter pylori, a bacterial pathogen that persistently colonizes the human stomach, from Western societies. In this study, we have utilized mouse models of allergic airway disease induced by ovalbumin or house dust mite allergen to experimentally examine a possible inverse correlation between H. pylori and asthma. H. pylori infection efficiently protected mice from airway hyperresponsiveness, tissue inflammation, and goblet cell metaplasia, which are hallmarks of asthma, and prevented allergen-induced pulmonary and bronchoalveolar infiltration with eosinophils, Th2 cells, and Th17 cells. Protection against asthma was most robust in mice infected neonatally and was abrogated by antibiotic eradication of H. pylori. Asthma protection was further associated with impaired maturation of lung-infiltrating dendritic cells and the accumulation of highly suppressive Tregs in the lungs. Systemic Treg depletion abolished asthma protection; conversely, the adoptive transfer of purified Treg populations was sufficient to transfer protection from infected donor mice to uninfected recipients. Our results thus provide experimental evidence for a beneficial effect of H. pylori colonization on the development of allergen-induced asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / complications
  • Asthma / microbiology*
  • Bronchoalveolar Lavage
  • Dendritic Cells / cytology
  • Disease Models, Animal
  • Helicobacter Infections / complications*
  • Helicobacter Infections / metabolism*
  • Helicobacter pylori / metabolism*
  • Hypersensitivity / complications
  • Hypersensitivity / microbiology*
  • Inflammation
  • Lung / cytology
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / cytology*
  • Th17 Cells / cytology
  • Th2 Cells / cytology