CFTR as a therapeutic target for severe lung infection

Lung infection is one of the leading causes of morbidity and mortality worldwide. Even with appropriate antibiotic and antiviral treatment, mortality in hospitalized patients often exceeds 10%, highlighting the need for the development of new therapeutic strategies. Of late, cystic fibrosis transmembrane conductance regulator (CFTR) is – in addition to its well-established roles in the lung airway and extrapulmonary organs – increasingly recognized as a key regulator of alveolar homeostasis and defense. In the alveolar epithelium, CFTR mediates alveolar fluid secretion and liquid homeostasis; in the microvascular endothelium, CFTR maintains vascular barrier function. CFTR also contributes to alveolar immunity. Yet, in lung infection, diverse molecular mechanisms reduce CFTR abundance and otherwise impair its function, promoting alveolar inflammation, edema, and cell death. Preservation or restoration of CFTR function by CFTR modulator drugs thus presents a promising avenue to combat lung infection in a pathogen-independent manner.