Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109-5688, USA.
Curr Opin Pulm Med. 2013 Mar;19(2):125-32. doi: 10.1097/MCP.0b013e32835cef10.
The aim is to understand how airway epithelial cells with compromised innate defense mechanisms enhance susceptibility to respiratory virus infections in chronic obstructive pulmonary disease (COPD).
Exacerbations associated with respiratory viruses are more severe and increase disease severity in COPD. Airway epithelial cells cultured from COPD patients show excessive innate immune response to viral infection and higher viral load compared with normal cells.
Airway epithelial cells are the first line of defense in the lung and are equipped with several lines of innate defense mechanisms to fight against invading pathogens including viruses. Under normal conditions, mucociliary and barrier functions of airway epithelial cells prevent virus binding and entry into the cells. Virus-infected airway epithelial cells also express various cytokines, which recruit and activate innate and adaptive immune cells ultimately controlling the infection and tissue damage. In COPD however, compromised mucociliary and barrier functions may increase virus binding and allow virus entry into airway epithelial cells. Virus-infected COPD airway epithelial cells also show disproportionate cytokine expression leading to inappropriate recruitment and activation of innate and adaptive immune cells. COPD airway epithelial cells also show defective antiviral responses. Such defects in innate defense mechanisms may increase susceptibility to viral infections and disease severity in COPD.
本综述旨在探讨气道上皮细胞固有防御机制受损如何增强慢性阻塞性肺疾病(COPD)患者对呼吸道病毒感染的易感性。
与呼吸道病毒相关的加重事件在 COPD 中更为严重,并增加了疾病的严重程度。与正常细胞相比,COPD 患者培养的气道上皮细胞对病毒感染表现出过度的固有免疫反应和更高的病毒载量。
气道上皮细胞是肺部的第一道防线,配备了多种固有防御机制,以抵御包括病毒在内的入侵病原体。在正常情况下,气道上皮细胞的黏液纤毛和屏障功能可防止病毒结合和进入细胞。感染病毒的气道上皮细胞还表达各种细胞因子,招募和激活固有免疫和适应性免疫细胞,最终控制感染和组织损伤。然而,在 COPD 中,黏液纤毛和屏障功能受损可能会增加病毒结合并允许病毒进入气道上皮细胞。感染病毒的 COPD 气道上皮细胞还表现出不成比例的细胞因子表达,导致固有免疫和适应性免疫细胞的募集和激活不当。COPD 气道上皮细胞还表现出抗病毒反应缺陷。固有防御机制的这些缺陷可能会增加 COPD 患者对病毒感染的易感性和疾病严重程度。