Kicic A, Stevens P T, Sutanto E N, Kicic-Starcevich E, Ling K-M, Looi K, Martinovich K M, Garratt L W, Iosifidis T, Shaw N C, Buckley A G, Rigby P J, Lannigan F J, Knight D A, Stick S M
Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, WA, Australia.
School of Paediatrics and Child Health, The University of Western Australia, Nedlands, WA, Australia.
Clin Exp Allergy. 2016 Nov;46(11):1441-1455. doi: 10.1111/cea.12767. Epub 2016 Jul 1.
The airway epithelium forms an effective immune and physical barrier that is essential for protecting the lung from potentially harmful inhaled stimuli including viruses. Human rhinovirus (HRV) infection is a known trigger of asthma exacerbations, although the mechanism by which this occurs is not fully understood.
To explore the relationship between apoptotic, innate immune and inflammatory responses to HRV infection in airway epithelial cells (AECs) obtained from children with asthma and non-asthmatic controls. In addition, to test the hypothesis that aberrant repair of epithelium from asthmatics is further dysregulated by HRV infection.
Airway epithelial brushings were obtained from 39 asthmatic and 36 non-asthmatic children. Primary cultures were established and exposed to HRV1b and HRV14. Virus receptor number, virus replication and progeny release were determined. Epithelial cell apoptosis, IFN-β production, inflammatory cytokine release and epithelial wound repair and proliferation were also measured.
Virus proliferation and release was greater in airway epithelial cells from asthmatics but this was not related to the number of virus receptors. In epithelial cells from asthmatic children, virus infection dampened apoptosis, reduced IFN-β production and increased inflammatory cytokine production. HRV1b infection also inhibited wound repair capacity of epithelial cells isolated from non-asthmatic children and exaggerated the defective repair response seen in epithelial cells from asthmatics. Addition of IFN-β restored apoptosis, suppressed virus replication and improved repair of airway epithelial cells from asthmatics but did not reduce inflammatory cytokine production.
Collectively, HRV infection delays repair and inhibits apoptotic processes in epithelial cells from non-asthmatic and asthmatic children. The delayed repair is further exaggerated in cells from asthmatic children and is only partially reversed by exogenous IFN-β.
气道上皮形成了一道有效的免疫和物理屏障，这对于保护肺部免受包括病毒在内的潜在有害吸入性刺激至关重要。人鼻病毒（HRV）感染是已知的哮喘发作诱因，尽管其发生机制尚未完全明确。
探讨哮喘患儿和非哮喘对照儿童的气道上皮细胞（AECs）对HRV感染的凋亡、固有免疫和炎症反应之间的关系。此外，检验HRV感染会进一步失调哮喘患者上皮异常修复的这一假说。
从39名哮喘儿童和36名非哮喘儿童获取气道上皮刷片。建立原代培养并使其暴露于HRV1b和HRV14。测定病毒受体数量、病毒复制及子代释放情况。还检测了上皮细胞凋亡、IFN-β产生、炎症细胞因子释放以及上皮伤口修复和增殖情况。
哮喘患者气道上皮细胞中的病毒增殖和释放更多，但这与病毒受体数量无关。在哮喘儿童的上皮细胞中，病毒感染抑制了凋亡，降低了IFN-β产生，并增加了炎症细胞因子产生。HRV1b感染还抑制了非哮喘儿童分离出的上皮细胞的伤口修复能力，并加剧了哮喘患者上皮细胞中所见的缺陷修复反应。添加IFN-β可恢复凋亡、抑制病毒复制并改善哮喘患者气道上皮细胞的修复，但并未降低炎症细胞因子产生。
总体而言，HRV感染会延迟非哮喘和哮喘儿童上皮细胞的修复并抑制凋亡过程。哮喘儿童细胞中的延迟修复进一步加剧，且外源性IFN-β仅能部分逆转这一情况。
