The reason why children who grow up on dairy farms are less likely to suffer from allergies and asthma has been unravelled by a study.
Using mice and human samples, a team of scientists found that high-level exposure to bits of bacteria (endotoxin or lipopolysaccharide (LPS)) found in farm dust initially triggers an inflammatory response in the lungs of the animals but eventually goes on to protect them from asthma. The results of the study were published today in the journal Science.
Martijn J. Schuijs, the first author of the paper from the VIB Inflammation Research Center, Ghent, Belgium, and others tried to establish whether exposure to environmental endotoxin offered the protective effect against asthma in mice and also study the mechanism of protection.
To do this, they exposed mice to low dose of endotoxin every day for two weeks before challenging them with dust mites. While the mice exposed to endotoxins did not develop allergic features, the mice in the control group did.
“In the endotoxin-exposed mice, the epithelial cells lining the lungs made lower levels of proinflammatory molecules called cytokines when they encountered the dust mites; the mice also had fewer dendritic cells, the immune sentinels activated by cytokines,” notes an accompanying News piece.
The one that played a role in reducing the inflammatory response in the endotoxin-exposed mice was a particular anti-inflammatory enzyme called A20, which is made by the epithelial cells.
To reconfirm that the protective effect only worked in the presence of A20, mice that were engineered to lack the gene responsible for A20 in their lung epithelial cells developed asthma when exposed to endotoxin.
The researchers got similar results when they exposed mice lacking the gene responsible for A20 to farm dust that contains fragments of different bacteria, extracellular polysaccharides from fungi, to name a few.
They found that farm dust too mediates protection via epithelial A20 when mice were exposed to low dose of farm dust prophylactically every alternate day for two weeks.
To see if A20 had to be functional to confer protection and to test the mechanism of protection in humans, the researchers studied in vitro the reaction between endotoxin and human bronchial epithelial cells.
The human samples were taken from both healthy individuals and from people with asthma. The bronchial epithelial cells from healthy people when pre-exposed to endotoxins generated fewer inflammatory molecules characteristic of allergies than their asthmatic counterparts. Unlike healthy people, the level of A20 was lower in people who had asthma.
According to the News item, the researchers found that “among nearly 500 farm children, those carrying a mutation that lowers A20 activity were five times more likely to develop asthma.”
The researchers claim that the A20 exhibits a similar regulatory mechanism in the gut, where the microbiota colony “induces the expression of A20 shortly after birth” helping it to tolerate the beneficial microbes that help in food digestion.
According to the hygiene hypothesis, the rise in the number of allergy and asthma cases after World War II is due to reduced exposure to “infectious pressure.” The hygiene hypothesis assumes that it acts on the T cells of the immune system. But the present study shows that the site of action is in the structural cells of the airways.
The News article cites many people being critical of A20’s role in asthma and allergy. “Drinking unprocessed milk also seems to ward off asthma in kids, and that effect is unlikely to involve the lung epithelium,” Gary Huffnagle of the University of Michigan, Ann Arbor told Science . Richard Blumberg, a Harvard University immunologist told Science that he would “like to see the Ghent team show that the protective response lasts from birth into adulthood.”
