Researchers have pinpointed a new way that common molds can breakdown the lung’s protective tissue barrier and spur future asthma attacks, according to research published in the peer-reviewed journal Cell Host & Microbe.
In both mice and humans, an especially strong response to this initial damage was associated with developing an overreaction to future mold exposure and the constricted airways characteristic of asthma.
The work provides a new avenue of research for understanding and potentially preventing the development of asthma, which affects 25 million Americans. Mold sensitivities account for a quarter to half of asthma responses, so preventing the body from establishing allergic reactions to mold could significantly reduce the burden of the disease.
UW-Madison Professor of Pediatrics, Medicine, and Medical Microbiology and Immunology Bruce Klein and postdoctoral researcher Darin Wiesner published their findings March 3. They collaborated with researchers at the University of Chicago, University of Minnesota and Harvard Medical School to complete the work.
“Aspergillus is ubiquitous, it’s everywhere, and we’re inhaling spores with every breath we take,” says Klein. The team set out to understand how these otherwise harmless molds sensitize some individuals to develop a strong, asthmatic response to their spores.
The mold’s digestive enzymes were a natural target. Molds secrete these enzymes to digest proteins in their environment as they feed on decaying matter. One such enzyme, a protease called Alp1, is a known lung allergen and is secreted in large amounts by Aspergillus molds. But how Alp1 induces asthma has been a mystery for years.
Wiesner investigated if Alp1 could trigger a series of well-known allergic response pathways in the body. But he couldn’t find any evidence that Aspergillus Alp1 activated these allergic responses, which are often primed to respond to unique signatures of damaging microorganisms, such as pathogens.
“This idea that these ubiquitous fungi that aren’t primary pathogens could have evolved highly specific components just didn’t seem to make sense,” says Wiesner. “So it seemed more reasonable that these proteases one inhales into the lungs just cause damage. And the first thing that they interact with when they enter the lungs of both humans and mice are the epithelial cells.”