People with cystic fibrosis are prone to infections because of the thick mucus that clogs their airways. They are also prone to infections because their mucus and airway liquid does not have the same infection-fighting properties as normal mucus. Using a model reproducing a respiratory epithelium, researchers from the University of Geneva (UNIGE) have discovered that a film of liquid is sufficient to restore the airways’ seal and reduce the risk of bacterial infection in people with cystic fibrosis. Their findings present a potential alternative to current therapies.
Their findings are published in the journal Cells in a paper titled, “Surface Hydration Protects Cystic Fibrosis Airways from Infection by Restoring Junctional Networks.”
“Defective hydration of airway surface mucosa is associated with recurrent lung infection in cystic fibrosis (CF), a disease caused by CF transmembrane conductance regulator (CFTR) gene mutations,” the researchers wrote. “Whether the composition and/or presence of an airway surface liquid (ASL) is sufficient to prevent infection remains unclear.”
“While it was already known that mucus hydration and the presence of sufficiently tight junctions preserved the integrity of the airways, the mechanisms involved and the links between these two mechanisms remained mysterious, which hindered the development of new therapies,” explained Marc Chanson, PhD, a professor in the department of cell physiology and metabolism and the Geneva Centre for Inflammation Research at the UNIGE Faculty of Medicine, who led this research.
The researchers developed an in vitro model using human lung cells. In collaboration with the team of Christian van Delden, PhD, and Thilo Köhler, PhD, from the departments of medicine and of microbiology and molecular medicine at the UNIGE Faculty of Medicine, Chanson and his team compared the response of epithelial cells invalidated for CFTR to bacterial infection, to which either hydrated, healthy mucus or physiological saline solution had been added.
“We observed a similar response in both cases: the presence of liquid, whatever its composition, restored the airways and protected them from infection,” explained Juliette Simonin, PhD, a post-doctoral fellow in Chanson’s laboratory and first author of the study. “Surface hydration is sufficient to tighten the junctions between cells and protects the epithelium integrity from bacterial colonization, even when CFTR is not functioning.”
“Our results provide evidence that rehydration of the airway surface is beneficial. The challenge now is to find a simple way of doing this in all people with the disease, whatever the mutation involved,” concluded Chanson.
