Harnessing the hygiene hypothesis to prevent asthma

How do dirty environments protect against asthma?   (bigcityal/Flickr)

Certain infections in young children might shape their immune systems in a way that protects them from developing allergic asthma, says a new study in mice. The study shows how that may happen, and showed that the same effect can be achieved using a compound that can be made synthetically.

“Some infections appear to result in important protective effects against asthma,” says Dale Umetsu, of Children’s Hospital Boston’s Division of Immunology, a senior author of the paper. “But we certainly don’t want to give people dangerous infections to prevent asthma. So if we can understand how infections prevent asthma, we may be able to replicate the good parts and avoid the bad parts of infection and develop new treatments for children to prevent asthma.”

The findings provide a new immunological mechanism in support of the “hygiene hypothesis,” an idea born from surprising findings associating dirtier environments, such as polluted cities and farms, with a lower risk for asthma. The hygiene hypothesis is popularly cited as the reason why asthma has skyrocketed in wealthier countries as childhood infections have plummeted.

In Umetsu’s lab, influenza A infection of very young mice protected them as adults from developing airway hyperreactivity, a hallmark of asthma. Intriguingly, when first author Ya–Jen Chang gave young mice a glycolipid compound isolated from Helicobacter pylori — a bacterium best known for causing stomach ulcers and increasing the risk of gastric cancers — she saw the same protective effect.

Both the influenza A infection and the H. pylori glycolipid appeared to confer their benefits by expanding an immature cell type in the lung known as natural killer T (NKT) cells, among the first responders to many infections. That’s a twist in the story. Four years ago,  Umetsu’s team implicated NKT cells as a cause of asthma. This time, a subset of inhibitory NKT cells seem to prevent allergic reactions in the airways — if stimulated at the right time by the right infectious agents or the right glycolipid.

“Treatments focused on specifically expanding this inhibitory subset of cells in children might prevent the development of asthma,” says Umetsu, also professor of pediatrics at Harvard Medical School. The study was published online this week in the Journal of Clinical Investigation.

In a recent review, Umetsu and his co-authors describe a new era of asthma research that has emerged in the last five years, which may be good news for the 1 in 10 people who suffer from it. Most of the research has focused on the common allergic asthma and the underlying adaptive immune responses, which features immune cells that are slow to respond but are able to develop long-term memory, such as those stimulated by each year’s flu vaccine or those involved in seasonal allergies. Recent research shows that asthma is even more complex, with many environmental causes and different underlying pathways that can develop independently and can also co-exist and interact. The efforts to disentangle and understand these pathways will lead to new and effective therapies that can be targeted and personalized to the different clinical forms, Umetsu wrote.