COPD Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
Am J Respir Cell Mol Biol. 2018 Jun;58(6):717-726. doi: 10.1165/rcmb.2017-0265OC.
Respiratory syncytial virus (RSV) is associated with enhanced progression of chronic obstructive pulmonary disease (COPD) and COPD exacerbations. However, little is known about the role of IL-17 in RSV-induced lung injury. We first investigated the role of RSV infection in enhancing mucous cell hyperplasia (MCH) and airspace enlargement in the lungs of mice injured with elastase and LPS (E/LPS). Mice injured with E/LPS had an enhanced and prolonged neutrophilic response to RSV that was associated with decreased levels of type I IFN and increased levels of IL-17, IL-23, CXCL-1, granulocyte colony stimulating factor (GCSF), CXCL-5, and matrix metalloproteinase (MMP)-9. In addition, extent of MCH and mean weighted alveolar space were increased significantly in the lungs of E/LPS-injured mice infected with RSV compared with E/LPS-only or RSV-only controls. Interestingly, immunodepletion of IL-17 before viral infection diminished the RSV-driven MCH and airspace enlargement in the E/LPS-injured animals, suggesting that IL-17 may be a therapeutic target for MCH and airspace enlargement when enhanced by RSV infection.
呼吸道合胞病毒（RSV）与慢性阻塞性肺疾病（COPD）的进展和 COPD 加重有关。然而，关于白细胞介素 17（IL-17）在 RSV 诱导的肺损伤中的作用知之甚少。我们首先研究了 RSV 感染在弹性蛋白酶和脂多糖（E/LPS）损伤的小鼠肺部增强黏液细胞增生（MCH）和气道扩张中的作用。E/LPS 损伤的小鼠对 RSV 的中性粒细胞反应增强且持续时间延长，这与 I 型干扰素水平降低和 IL-17、IL-23、CXCL-1、粒细胞集落刺激因子（GCSF）、CXCL-5 和基质金属蛋白酶（MMP）-9 水平升高有关。此外，与 E/LPS 对照组或 RSV 对照组相比，E/LPS 损伤后感染 RSV 的小鼠肺部 MCH 和平均加权肺泡腔显著增加。有趣的是，病毒感染前的 IL-17 免疫耗竭可减少 E/LPS 损伤动物的 RSV 驱动的 MCH 和气道扩张，表明当 RSV 感染增强时，IL-17 可能是 MCH 和气道扩张的治疗靶点。
