Centre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia.
QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
Viruses. 2021 May 14;13(5):911. doi: 10.3390/v13050911.
IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV. BECs from five COPD and five healthy donors were used to establish both submerged monolayer and well-differentiated (WD) cultures. Two isolates of both RSV and hMPV were used to infect cells. COPD was not associated with elevated susceptibility to infection and there was no evidence of an intrinsic defect in IFN production in either cell model to either virus. Conversely, COPD was associated with significantly elevated IFN-β production in response to both viruses in both cell models. Only in WD-BECs infected with RSV was elevated IFN-β associated with reduced viral shedding. The role of elevated epithelial cell IFN-β production in the pathogenesis of COPD is not clear and warrants further investigation. Viruses vary in the responses that they induce in BECs, and so conclusions regarding antiviral responses associated with disease cannot be made based on single viral infections.
基于 COPD 中 IFN 缺乏的证据,IFN 治疗可能是治疗 COPD 加重的一种可行选择。然而,体外研究主要使用流感病毒和鼻病毒来研究 IFN 反应。本研究旨在研究 COPD 供体的原代支气管上皮细胞 (BEC) 对 RSV 和 hMPV 感染的易感性和 IFN 反应。使用来自五名 COPD 患者和五名健康供体的 BEC 来建立浸没单层和分化良好 (WD) 培养物。使用两种 RSV 和 hMPV 的分离株感染细胞。COPD 与感染易感性升高无关,并且在两种细胞模型中都没有证据表明 IFN 产生存在内在缺陷。相反,COPD 与两种细胞模型中对两种病毒的 IFN-β 产生均显著升高有关。只有在感染 RSV 的 WD-BEC 中,升高的 IFN-β 与病毒脱落减少有关。上皮细胞 IFN-β 产生增加在 COPD 发病机制中的作用尚不清楚,需要进一步研究。病毒在诱导 BEC 产生的反应方面存在差异,因此不能基于单一病毒感染来得出与疾病相关的抗病毒反应的结论。