A bacterium that causes ulcers and stomach cancers may protect against asthma by teaching the immune system tolerance, a new study in mice shows.
Stomach cancer cases have dropped in North America and Europe as the number of people who carry the bacterium Helicobacter pylori has declined. At the same time, in places where the stomach bacterium is becoming scarce, rates of asthma have increased. Despite suspicions of a connection, hard evidence that the disappearance of the bacterium could be responsible for soaring asthma rates was lacking. “It was just sort of making links,” says gastroenterologist John Atherton of the University of Nottingham in England, “but not really showing cause and effect.”
Now, a group of European researchers led by Anne Müller of the University of Zurich report online February 6 in the Journal of Clinical Investigation that Helicobacter coaxes immune cells to tolerate bacterial infections instead of fighting off bacteria with inflammation. The immune-system calming effect helps ward off asthma, which is caused by inflammation in the airways.
Previously, Müller’s group had discovered that infections with Helicobacter pylori cause young mice to make inflammation-dampening immune cells called regulatory T cells instead of inflammation-producing T cells. In the new study, Müller and her colleagues take a step back to find out how the bacteria shift the inflammation balance.
Helicobacter reprograms immune cells called dendritic cells so they take a tolerant view of the stomach bacterium, the researchers learned from experiments with young mice. The dendritic cells then shift the balance of T cells toward regulatory cells, the researchers find. That inflammation-dampening response, which the bacterium uses to protect itself from immune system attack, also helps protect the host against asthma.
In the study, mice did not develop asthma if infected with the bacterium. “It’s absolutely a protective infection,” Müller says.
People who have Helicobacter in their stomachs, but do not have ulcers or stomach cancer, also have inflammation-dampening dendritic cells, the team shows. Müller suspects that dendritic cells from people who have ulcers or stomach cancer would be of the inflammatory variety, she says. If something impedes a friendly relationship between Helicobacter and its host, inflammation results, leading to tissue damage that can produce ulcers or spark cancer, Müller proposes.
The new work “really cements the idea that Helicobacter disease is a host-driven pathology,” says Jay Solnick, a microbiologist and infectious disease physician at the University of California, Davis.
Whether Helicobacter is good or bad may depend a lot on a person’s age, says Martin Blaser, a microbiologist at New York University School of Medicine. Blaser was one of the first people to notice that a decline in Helicobacter infections was linked to a rise in asthma cases. He says that the bacterium may be important for teaching children’s immune systems not to overreact to friendly bacteria. But it could become a problem for some adults.
The new work is “an important link in the chain of evidence” linking Helicobacter and asthma, Blaser says. “It’s becoming clearer and clearer that Helicobacter has benefits in addition to its costs.”
But no one is suggesting that children should be infected with Helicobacter to protect them from asthma.
For now, “the advantages of not having it outweigh the disadvantages,” says Atherton. Stomach cancer is so dangerous that “you would need to protect against an awful lot of asthma to make up for it.”
Müller hopes to discover the molecules Helicobacter uses to reprogram the immune system, so people could reap the rewards of the bacterium without having to deal with the drawbacks.
