Editors' ChoiceMicrobiology

Infections with benefits

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Science Translational Medicine  24 Feb 2016:
Vol. 8, Issue 327, pp. 327ec31
DOI: 10.1126/scitranslmed.aaf3852

Although the majority of the world’s population carry a Helicobacter pylori infection without any symptoms, this bacterium has earned a bad reputation because of its causative association with stomach inflammation and peptic ulcer disease—a discovery that earned Marshall and Warren the 2005 Nobel Prize in Physiology and Medicine. However, accumulating evidence suggests that H. pylori can have unexpected health benefits, particularly in the young, including protection against asthma, certain types of infections, and esophageal diseases. Now, Kienesberger et al. describe some of the details of the complex host response to H. pylori colonization.

The researchers established long-term, stable H. pylori infections in two cohorts of relatively young mice—one 4 weeks of age, just after weaning, and another at sexual maturity (6 weeks). Analysis of the mice at 1, 2, 3, and 6 months after infection showed that infected animals’ stomachs had an inflammatory reaction, which was histologically very similar to that observed in humans. The mouse model also recapitulated the human endocrine response to H. pylori with elevated plasma concentrations of ghrelin, a versatile gut hormone that affects appetite, metabolism, and even the immune system. A comprehensive look at how the infection affected the expression of 547 genes related to the immune response in the stomach showed many changes, including persistent up-regulation of proinflammatory and T cell activation genes, as well as other temporally dynamic responses that may reveal clues about how the immune system adapts to persistent infection in parallel with aging. Kienesberger and colleagues also described a changed composition of the microbiota “ecosystem,” both in the stomach and downstream in the intestines of infected animals. This could be a cause or a consequence of the diverse host responses.

A systemic manifestation of H. pylori infection in the stomach was implied by the change in ghrelin concentration, but by looking at the lung more closely, the authors determined that other organ systems are also affected. Analysis of immune cell populations in the lung revealed modestly more TH17 (proinflammatory T helper) cells, and a trend toward more regulatory T cells in infected mice. As for immune-related gene expression in the lung, there were only a few consistent changes, but early time points showed up-regulation of many potentially influential genes, such as receptors for TGF-β, IL-4, and IL-6.

It is interesting to question whether the systemic and generally immunosuppressive response observed in this study is specific to H. pylori. It also remains to be seen whether this microorganism-triggered immune response, which likely evolved to facilitate bacterial survival, underpins the epidemiological link between H. pylori and reduced susceptibility to other conditions such as asthma.

S. Kienesberger et al., Gastric Helicobacter pylori infection affects local and distant microbial populations and host responses. Cell Rep. 14, 1–13 (2016). [Full Text]

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