Editors' ChoiceAsthma

A Gut Check for Asthma

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Science Translational Medicine  31 Aug 2011:
Vol. 3, Issue 98, pp. 98ec142
DOI: 10.1126/scitranslmed.3003109

Asthma—airway inflammation characterized by wheezing, coughing, and shortness of breath—affects 22 million people in the United States. It has been postulated that the rise of asthma in Western countries is due to a decrease in the exposure of infants to “germs” required to properly “educate” the immune system, the so-called hygiene hypothesis. In support of this theory, epidemiological studies have documented an inverse association between the presence of the gastric pathogen, Helicobacter pylori, and the risk of developing asthma. Given the widespread use of antibiotic therapy in industrialized countries, there has been a dramatic reduction in the prevalence of H. pylori in the human gut microbiota. Now, Arnold et al. demonstrate that mice infected with H. pylori are protected against asthma through induction of suppressive regulatory T cells (Treg cells) in the lungs.

First, the investigators infected neonatal and adult mice with H. pylori. Then, they exposed the animals to ovalbumin followed by an ovalbumin challenge 4 weeks later, which is a well-established technique for inducing asthma in animal models. They found that compared with uninfected mice, animals infected with H. pylori showed a reduction in several hallmarks of allergic airway inflammation, including lung eosinophil count, the cytokines interleukin-5 (IL-5) and IL-13, and airway hyperresponsiveness. Next, the authors demonstrated that eradicating H. pylori infection in neonatal mice by using antibiotics resulted in the mice developing asthma after ovalbumin exposure and challenge. In order to identify a cellular mechanism for this process, they examined Treg cells in their mouse model because these cells have a known role in reducing allergic airway inflammation. They demonstrated that infected neonatal mice had the highest numbers of Treg cells in their lungs and also the highest numbers of semi-mature dendritic cells, an immune cell population that is believed to boost peripheral Treg cell expansion. Last, to confirm an important functional role for Treg cells, they showed that depleting infected mice of Treg cells worsened allergic inflammation after ovalbumin exposure and challenge, and that adoptively transferring Treg cells into mice conferred protection against allergic airway disease. H. pylori is an important component of the human gut microbiota that is often singled out for its role in causing stomach ulcers and in some cases gastric cancer. The interesting study of Arnold et al. now highlights a potential beneficial role for H. pylori in protecting against allergic airway disease and suggests that overuse of antibiotics has helped to eradicate H. pylori, thus potentially contributing to the rise in asthma.

I. C. Arnold et al., Helicobacter pylori infection prevents allergic asthma in mouse models through the induction of regulatory T cells. J. Clin. Invest. 121, 3088–3093 (2011). [Full Text]

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