More farm, less pharma (Image: Julia Christe/plainpicture)
Dirt is good for you: kids on farms are less likely to develop allergies and asthma than urban children, for example. But the protective effects of friendly microbes seem to depend equally on a person’s genetic make-up.
The idea that a lack of exposure to dirt and microbes is to blame for increases in childhood allergies and asthma is known as the hygiene hypothesis. As for the underlying mechanism, there’s evidence that a bacterial protein called endotoxin is important for damping down overactive immune systems.
Endotoxin is found on the surface of many species of common bacteria, like Escherichia coli. These common bacteria are even more abundant in farm environments, especially dairy farms. But new experiments in mice suggest that one of our own enzymes, A20, is also essential for protecting against allergies, and those who lack this enzyme don’t benefit from exposure to endotoxin.
Dust mite test
A20 plays a role in controlling inflammation and is activated in newborn babies when they come into contact with benign bacteria in the birth canal. Evidence suggests the enzyme helps teach a baby’s immune system not to overreact to harmless microbes.
Children with gene mutations that disrupt the functioning of A20 are more likely to have asthma and allergies, so Bart Lambrecht of Ghent University in Belgium and his team wondered whether A20 may be involved helping endotoxins to train our immune systems.
They decided to look at the effects of endotoxin in normal mice, and in those who had been genetically engineered to lack the enzyme. After exposing both types of mice to endotoxin for two weeks, they tested their sensitivity to house dust mites, a common cause of allergies in both mice and humans.
They found that normal mice had no allergic responses to the mites, although some normal mice from a control group not exposed to endotoxin did. However, endotoxin exposure did not stop mice lacking the A20 enzyme from becoming allergic to mites, showing that both the bacterial protein and the enzyme are needed to ensure the immune system did not overreact.
When the team turned to human lung cells, they found that A20 was also less active in adults with asthma.
“It’s important because it shows that endotoxin can’t work on its own,” says Erika von Mutius of the Ludwig Maximilian University in Munich, Germany, a leading proponent of the hygiene hypothesis. Her earlier work suggested that a tolerance for endotoxin is what protects children raised on farms, and this new study provides strong support for this protein’s role in guarding against allergies.
But William Parker at Duke University Medical Center in Durham, North Carolina, doesn’t think endotoxin can explain why modern city-dwellers have such overactive immune systems. “Even the cleanest humans are still bathed in endotoxin,” he says.
Instead, Parker believes a lack of exposure to parasites like lice and worms is to blame. “The virtually complete loss of contact with organisms such as intestinal worms that don’t produce endotoxin is known to be an important contributor to the over-inflammatory state of Western immune systems,” he says.
Journal reference: Science, DOI: 10.1126/science.aac6623
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