Hook Jaime L, Kuebler Wolfgang M
Lung Imaging Laboratory, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States.
Am J Physiol Lung Cell Mol Physiol. 2025 Feb 1;328(2):L229-L238. doi: 10.1152/ajplung.00289.2024. Epub 2025 Jan 8.
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.
肺部感染是全球发病和死亡的主要原因之一。即使采用适当的抗生素和抗病毒治疗，住院患者的死亡率通常仍超过10%，这凸显了开发新治疗策略的必要性。近来，囊性纤维化跨膜传导调节因子（CFTR）除了在肺气道和肺外器官中已确立的作用外，越来越被认为是肺泡稳态和防御的关键调节因子。在肺泡上皮中，CFTR介导肺泡液体分泌和液体稳态；在微血管内皮中，CFTR维持血管屏障功能。CFTR也有助于肺泡免疫。然而，在肺部感染中，多种分子机制会降低CFTR丰度并以其他方式损害其功能，从而促进肺泡炎症、水肿和细胞死亡。因此，通过CFTR调节剂药物保存或恢复CFTR功能，为以不依赖病原体的方式对抗肺部感染提供了一条有前景 的途径。
