Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells
Isabelle C. Arnold, … , Christian Taube, Anne Müller
Isabelle C. Arnold, … , Christian Taube, Anne Müller
Published August 1, 2011; First published July 1, 2011
Citation Information: J Clin Invest. 2011;121(8):3088-3093. https://doi.org/10.1172/JCI45041.
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Brief Report

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

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.

Authors

Isabelle C. Arnold, Nina Dehzad, Sebastian Reuter, Helen Martin, Burkhard Becher, Christian Taube, Anne Müller

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Figure 1

Experimentally induced asthma is alleviated by H. pylori infection.

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Experimentally induced asthma is alleviated by H. pylori infection. ...
Mice were orally infected as neonates (iN) or adults (iA) with H. pylori and sensitized with alum-adjuvanted OVA (A–G) or HDM (H–M) 4 and 6 weeks after infection along with an uninfected (uninf) group. 1 group of neonatally infected mice received antibiotic therapy between the first and second allergen doses. 2 weeks after the second sensitization, all mice (including a mock-sensitized control group [PBS]) were exposed to 3 consecutive daily doses of aerosolized OVA or intranasal HDM. (A, H) Airway hyperresponsiveness in response to increasing doses of methacholine and the highest dose of 100 mg/ml, respectively (upper and lower panels in A). (B, C, I, and J) Tissue inflammation and goblet cell metaplasia as assessed on H&E- and PAS-stained tissue sections. Representative micrographs are shown in B and I; inflammation and PAS scores are shown in C and J. Original magnification, ×100 (H&E); ×400 (PAS). (D and K) Total cells contained in 1 ml of BALF. (E) Relative representation of the indicated cell types in BALF. (F and L) Absolute numbers of eosinophils in 1 ml of BALF. (G and M) IL-5 and/or IL-13 secretion as assessed by cytometric bead array. *P < 0.05 and **P < 0.01 in comparison with uninfected, but allergen-treated, controls. All group data of methacholine measurements are presented as mean ± SEM. Total cell and eosinophil counts in BALF are presented for individual mice, with horizontal bars indicating group medians. Inflammation scores and PAS+ cells are represented by box and whisker plots, with horizontal bars representing medians and whisker ends indicating minimal and maximal values. Cytokine measurements and PCR results are presented as group mean ± SD.