Each time you take a breath, there’s a good chance you’re inhaling bits of insects, morsels of mites, and other remnants of various organisms. This debris is rich in a molecule called chitin, the main ingredient of insect skeletons, whose impact on our health has puzzled researchers. A new study bolsters the case that chitin promotes lung diseases. But the study also suggests that an enzyme that breaks down chitin staves off these illnesses, potentially leading to a new class of drugs that could help combat them.
“It's very significant work,” says immunologist Geoffrey Chupp of Yale School of Medicine, who wasn’t involved in the research. “It’s one of the first studies that shows evidence that there’s chitin present in patients who develop a lung disease.”
Chitin is a sturdy sugar molecule found in everything from crab shells to the eggs of parasitic worms to the cell walls of fungi. Some data suggest that AMCase, an enzyme that breaks down chitin, may defend us from the molecule. People who carry an overactive variety of AMCase are less likely to develop asthma, for instance.
To test the enzyme’s role in protecting against lung disease, immunologists Steven Van Dyken and Richard Locksley of the University of California, San Francisco, and colleagues created genetically altered mice that can’t produce AMCase. As these mice aged, they began to have difficulty breathing and started to die, the team reports today in Cell. Less than half the animals survived for 2 years, whereas almost all the control rodents did. The lungs of older AMCase-lacking mice absorbed less oxygen than normal. They also showed signs of inflammation and fibrosis, the buildup of scar tissue. In humans, pulmonary fibrosis can also hamper oxygen absorption by the lungs.
The team found that these problems stemmed from a common cause: the animals’ inability to break down chitin. In older mice that are missing AMCase, the airways contained more chitin than did the airways of control rodents of the same age. At first, its source was a mystery, because the mice lived in sterile surroundings and breathed filtered air. “We thought we were dealing with a clean environment,” Van Dyken says. But as the researchers discovered, even the animals’ food and bedding material contained chitin.
Restoring the levels of AMCase—either by genetically modifying the animals to manufacture the enzyme again or by squirting it into their nostrils—was beneficial, even in older mice; the amount of fibrosis and lung inflammation declined.
To test whether chitin promotes lung disease in people, the researchers measured its abundance in samples of airway fluid from patients with interstitial lung disease (ILD), who often have fibrosis as well. ILD can result from exposure to certain toxins, but often the cause isn’t clear. Compared with healthy people, the patients with ILD harbored twice as much chitin in their airways. However, the ILD patients didn’t have a shortage of AMCase, and Van Dyken says the scientists are trying to determine why chitin is prevalent in these individuals. “We think that the particles [of chitin] are not cleared normally the way they are in a healthy person.”
“I applaud the use of the aged mice” in the study, says immunologist Dominik Hartl of the University of Tübingen in Germany. Many researchers only use young mice, he says, but chitin’s effects only appeared as the animals aged. But he cautions that “it is too early to say” that chitin plays an important role in human disease.
Chupp says that researchers need to learn more about where the chitin in the lungs of patients comes from and how it might drive disease. If studies can confirm that chitin promotes lung illnesses, Van Dyken notes that it might be possible to treat them with inhaled AMCase, much like the researchers did with the aged mice.