Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; however, apoptosis of lung alveolar epithelial cells plays a role in disease progression. This intractable disease is associated with increased abundance of Staphylococcus and Streptococcus in the lungs, yet their roles in disease pathogenesis remain elusive. Here, we report that Staphylococcus nepalensis releases corisin, a peptide conserved in diverse staphylococci, to induce apoptosis of lung epithelial cells. The disease in mice exhibits acute exacerbation after intrapulmonary instillation of corisin or after lung infection with corisin-harboring S. nepalensis compared to untreated mice or mice infected with bacteria lacking corisin. Correspondingly, the lung corisin levels are significantly increased in human IPF patients with acute exacerbation compared to patients without disease exacerbation. Our results suggest that bacteria shedding corisin are involved in acute exacerbation of IPF, yielding insights to the molecular basis for the elevation of staphylococci in pulmonary fibrosis.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; apoptosis of lung alveolar epithelial cells plays a role in disease progression
We demonstrated that the lung fibrotic tissue from IPF patients and from transforming growth factor (TGF)β1 transgenic (TG) mice with lung fibrosis is characterized by an enrichment of halophilic bacteria, and a subsequent report has substantiated our observation[8,9]
Abnormal extracellular storage of salt may result from TGFβ1-mediated negative regulation of the surface expression of epithelial sodium and chloride channels leading to decreased transport of Na+ and Cl− ions from the alveolar airspaces across the epithelium[25,26,27,28,29]
Summary
Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal disease of unknown etiology; apoptosis of lung alveolar epithelial cells plays a role in disease progression This intractable disease is associated with increased abundance of Staphylococcus and Streptococcus in the lungs, yet their roles in disease pathogenesis remain elusive. We demonstrated that the lung fibrotic tissue from IPF patients and from transforming growth factor (TGF)β1 transgenic (TG) mice with lung fibrosis is characterized by an enrichment of halophilic bacteria, and a subsequent report has substantiated our observation[8,9] These results led us to hypothesize that the fibrotic tissue is a salty microenvironment, and that the hypersaline condition of the lung fibrotic tissue facilitates the growth of bacteria that release factors that play a role in disease pathogenesis and its acute exacerbation
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