Helicobacter pylori immunotherapy protects mice from the development of allergic asthma

Abstract

Background: Helicobacter pylori are the dominant member of the gastric microbiota and have intimately co-evolved with humans since their migration out of Africa. Epidemiological studies show that this bacterium could be beneficial to the host with increasing evidence of H. pylori-mediated protection against inflammatory conditions such as childhood asthma and allergies and inflammatory bowel disease. H. pylori is associated with a reduced risk of allergic disease and this correlation is greater for infection acquired early in life suggesting that H. pylori have a favourable effect on immune system development. Methods: Live or inactivated H. pylori were administered to adult or neonate mice prior to the induction of ovalbumin (OVA)-induced allergic airways disease. Assessment of airway hyper-responsiveness, OVA-specific IgE and pro-inflammatory cytokines was performed. Results: Our data confirmed epidemiological findings and shows that H. pylori protects mice against the development of allergic asthma in adult and neonate models. Furthermore, we show that inactivated H. pylori retain their immune-suppressive features and also confer protection from allergic disease in mice, demonstrating that constituents of H. pylori are sufficient to confer the protective effects. Administration of live or inactivated H. pylori resulted in reduced airway hyper-responsiveness, reduced OVA-specific IgE in the serum and lower levels of pro-inflammatory cytokines in the lungs. Although the mechanisms underlying the protective effects of live or inactivated H. pylori remain unclear, in accordance with others, we observed that H. pylori-mediated immune suppression renders dendritic cells semimature and promotes a tolerogenic state. Conclusions: Our findings support the notion that early-life exposure to H. pylori can contribute to balanced immune system development and function and warrants further investigation into the underlying mechanisms of H. pylori-mediated immune modulation of its host particularly in the context of immunotherapy for the treatment of inflammatory diseases such as allergy.