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Neutrophil responses to RSV infection show differences between infant and adult neutrophils
Thorax ( IF 10 ) Pub Date : 2024-02-16 , DOI: 10.1136/thorax-2023-220081
Elisabeth Robinson , Shyam Sawhney , Mario Cortina-Borja , Anna L David , Claire M Smith , Rosalind L Smyth

Introduction Respiratory syncytial virus (RSV) causes a severe respiratory condition, bronchiolitis, in infants but not in adults. Bronchiolitis is characterised by neutrophilic infiltration in the airways, but whether neutrophils enhance recovery from infection or contribute to its pathology remains unknown. Methods We used a novel in-vitro model to compare term umbilical cord blood (infant) (n=17 donors) and adult neutrophils (n=15 donors) during migration across RSV-infected differentiated human nasal airway epithelial cells (AECs) in a basolateral to apical direction. Results Greater numbers of infant neutrophils (mean (95% CI)) (336 684 (242 352 to 431 015)) migrated across RSV-infected AECs to the apical compartment (equivalent to the airway lumen) compared with adult neutrophils (56 586 (24 954 to 88 218)) (p<0.0001). Having reached the apical compartment of infected AECs, much greater numbers of infant neutrophils (140 787 (103 117 to 178 456)) became apoptotic compared with adult (5853 (444 to 11 261)) (p=0.002). Infant neutrophils displayed much greater expression of CD11b, CD64, neutrophil elastase (NE) and myeloperoxidase (MPO) than adult neutrophils at baseline and at all points of migration. However, as adult neutrophils migrated, expression of CD11b, CD64, NE and MPO became greater than at baseline. Discussion The high proportion of infant neutrophils migrating across RSV-infected AECs correlates with the neutrophilic infiltrate seen in infants with severe RSV bronchiolitis, with large numbers undergoing apoptosis, which may represent a protective mechanism during infection. Compared with adult neutrophils, infant neutrophils already have high expression of surface markers before contact with AECs or migration, with less capacity to increase further in response to RSV infection or migration. All data relevant to the study are included in the article or uploaded as supplementary information.

中文翻译:

中性粒细胞对 RSV 感染的反应显示婴儿和成人中性粒细胞之间的差异

简介 呼吸道合胞病毒 (RSV) 会在婴儿中引起严重的呼吸道疾病(细支气管炎),但不会在成人中引起。细支气管炎的特征是气道中的中性粒细胞浸润,但中性粒细胞是否促进感染恢复或导致其病理学仍不清楚。方法 我们使用一种新型体外模型来比较足月脐带血(婴儿)(n = 17 名供体)和成人中性粒细胞(n = 15 名供体)在 RSV 感染的分化人鼻气道上皮细胞 (AEC) 中迁移的过程。基底外侧到顶端方向。结果 与成人中性粒细胞(56 586 例)相比,更多数量的婴儿中性粒细胞(平均值(95% CI))(336 684 例(242 352 至 431 015 例))穿过 RSV 感染的 AEC 迁移至心尖区(相当于气道腔)。 24 954 至 88 218)) (p<0.0001)。到达受感染 AEC 的顶室后,与成人 (5853 (444 至 11 261)) 相比,更多数量的婴儿中性粒细胞 (140 787 (103 117 至 178 456)) 发生凋亡 (p=0.002)。在基线和所有迁移点,婴儿中性粒细胞表现出比成人中性粒细胞更高的 CD11b、CD64、中性粒细胞弹性蛋白酶 (NE) 和髓过氧化物酶 (MPO) 表达。然而,随着成年中性粒细胞迁移,CD11b、CD64、NE 和 MPO 的表达变得高于基线。讨论 婴儿中性粒细胞在 RSV 感染的 AEC 中迁移的比例较高,与患有严重 RSV 细支气管炎的婴儿中观察到的中性粒细胞浸润相关,其中大量细胞凋亡,这可能代表感染期间的保护机制。与成人中性粒细胞相比,婴儿中性粒细胞在接触 AEC 或迁移之前就已经具有高表达的表面标志物,而响应 RSV 感染或迁移而进一步增加的能力较小。与研究相关的所有数据都包含在文章中或作为补充信息上传。
更新日期:2024-02-17
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