Neutrophil-Airway Epithelial Interactions Result in Increased Epithelial Damage and Viral Clearance during Respiratory Syncytial Virus Infection
Neutrophil-Airway Epithelial Interactions Result in Increased Epithelial Damage and Viral Clearance during Respiratory Syncytial Virus Infection
复制标题
中性粒细胞-气道上皮相互作用导致呼吸道合胞病毒感染期间上皮损伤和病毒清除增加
DOI：
10.1128/jvi.02161-19
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发表时间：
2020-07-01
影响因子：
5.4
通讯作者：
Smith, Claire M.
中科院分区：
文献类型：
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作者：
Deng, Yu;Herbert, Jenny A.;Smith, Claire M.
呼吸道合胞病毒(RSV)是引起儿童呼吸道疾病的主要原因。患有严重呼吸道合胞病毒病的儿童的呼吸道中招募了大量的中性粒细胞。目前尚不清楚中性粒细胞是否或如何促进疾病的恢复或参与其病理过程。利用体外分化的呼吸道上皮细胞模型，我们发现，在RSV感染的鼻腔培养物中加入生理浓度的中性粒细胞与更大的上皮损伤有关，纤毛活动较低，纤毛丢失，紧密连接表达(ZO-1)较少，上皮细胞脱离较多。这也与中性粒细胞暴露后培养物中感染性病毒的减少和RSV阳性细胞的减少有关。呼吸道合胞病毒感染引起的上皮损伤与中性粒细胞活化(1h内)和中性粒细胞脱颗粒有关，与模拟感染的呼吸道上皮细胞(AECs)相比，CD11b和髓过氧化物酶的细胞表达显著增加，中性粒细胞弹性蛋白酶和髓过氧化物酶的活性显著升高。我们还从RSV感染的培养物(40%)中恢复了更多的凋亡中性粒细胞，而从模拟感染的培养物(
Respiratory syncytial virus (RSV) is a major cause of pediatric respiratory disease. Large numbers of neutrophils are recruited into the airways of children with severe RSV disease. It is not clear whether or how neutrophils enhance recovery from disease or contribute to its pathology. Using an in vitro model of the differenti-ated airway epithelium, we found that the addition of physiological concentrations of neutrophils to RSV-infected nasal cultures was associated with greater epithelial damage with lower ciliary activity, cilium loss, less tight junction expression (ZO-1), and more detachment of epithelial cells than is seen with RSV infection alone. This was also associated with a decrease in infectious virus and fewer RSV-positive cells in cultures after neutrophil exposure than in preexposure cultures. Epithelial damage in response to RSV infection was associated with neutrophil activation (within 1 h) and neutrophil degranulation, with significantly greater cellular expression of CD11b and myeloperoxidase and higher levels of neutrophil elastase and myeloperoxidase activity in apical surface media than in media with mock-infected airway epithelial cells (AECs). We also recovered more apoptotic neutrophils from RSV-infected cul-tures (40%) than from mock-infected cultures (