An international research team has identified an immune receptor that could play a key role in progressive lung damage and may serve as a novel therapeutic target for idiopathic pulmonary fibrosis (IPF). The team’s findings are detailed in the paper, “Toll-Like Receptor 5 Protects Against Murine Lung Fibrosis Through Reduced Dysbiosis, and TLR5 Deficiency Is Associated With Human IPF,” published in Science Translational Medicine.
Toll-like receptor 5 (TLR5) is responsible for recognizing dangerous bacteria and initiating protective responses in the immune system. The researchers’ goal was to prove an association between reduced TLR5 function and IPF.
First, the researchers analyzed genetic data of approximately 1,100 patients with IPF and 2,500 healthy individuals. Then, they corroborated their results in mouse models, observing that mice with TLR5 deficiency were at an increased risk of developing pulmonary fibrosis and lung dysbiosis.
Stavros Garantziotis, MDNIEHS
“Elimination of the microbiome in mice through administration of antibiotics abolished the protective effect of TLR5, and reconstitution of the microbiome by fecal microbiota transplantation rescued the observed phenotype,” the authors wrote. “In conclusion, these studies revealed that TLR5 protects against pulmonary fibrosis through effects on the lung microbiota, providing insight into therapeutic approaches that may ultimately benefit patients with IPF.”
Next steps, Dr. Garantziotis said, are to evaluate antibiotics that can restore healthy lung bacteria and determine which medicines could directly stimulate TLR5 function to prevent or reverse damage from pulmonary fibrosis.
