Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure
Reduced Nasal Viral Load and IFN Responses in Infants with Respiratory Syncytial Virus Bronchiolitis and Respiratory Failure
复制标题
DOI：
10.1164/rccm.201712-2567oc
复制
发表时间：
2018-10-15
影响因子：
24.7
通讯作者：
Openshaw, Peter
中科院分区：
文献类型：
--
作者：
Thwaites, Ryan S.;Coates, Matthew;Openshaw, Peter
原理：呼吸道合胞病毒（RSV）细支气管炎是婴儿期发病和死亡的主要原因。严重的疾病被认为是由于病毒复制失控，过度的免疫反应，或both. Objective.Objectives：通过对中度和重度毛细支气管炎病例在感染过程中的鼻液进行连续采样，确定鼻粘膜衬里液中RSV载量和免疫介质水平。2016年和2017年期间，从儿科中心招募了需要住院的病毒性细支气管炎婴儿（n = 55）。其中，30例为RSV感染（18例“中度”，12例机械通气“重度”）。随着时间的推移，使用鼻吸附装置和鼻咽抽吸频繁采集鼻液。进行时间加权平均值的层次聚类以研究细胞因子和趋化因子水平，并进行基因表达谱分析。出乎意料的是，严重RSV细支气管炎病例的鼻病毒载量较低，IFN-γ和C-C趋化因子配体5/RANTES降低，（在活化时调节，正常T细胞表达和分泌）水平高于中度疾病，尤其是考虑病程因素后（P均< 0.05）。严重疾病中细胞因子/趋化因子水平降低也见于其他病毒感染的儿童。鼻咽抽吸样本的基因表达分析（n = 43）证实了在严重毛细支气管炎中I型IFN基因表达降低，伴有MUC 5AC和IL 17 A表达增强。患有严重RSV细支气管炎的婴儿具有较低的鼻病毒载量，CXCL 10（C-X-C基序趋化因子配体10）/IP-10和I型IFN水平高于中度患病儿童，但鼻细胞中MUC 5AC（粘蛋白-5AC）和IL 17 A基因表达增强。
Rationale: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is believed to result from uncontrolled viral replication, an excessive immune response, or both.Objectives: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection.Methods: Infants with viral bronchiolitis necessitating admission (n = 55) were recruited from a pediatric center during 2016 and 2017. Of these, 30 were RSV infected (18 "moderate" and 12 mechanically ventilated "severe"). Nasal fluids were sampled frequently over time using nasosorption devices and nasopharyngeal aspiration. Hierarchical clustering of time-weighted averages was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted.Measurements and Main Results: Unexpectedly, cases with severe RSV bronchiolitis had lower nasal viral loads and reduced IFN-g and C-C chemokine ligand 5/RANTES (regulated upon activation, normal T cell expressed and secreted) levels than those with moderate disease, especially when allowance was made for disease duration (all P < 0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of nasopharyngeal aspiration samples (n = 43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A.Conclusions: Infants with severe RSV bronchiolitis have lower nasal viral load, CXCL10 (C-X-C motif chemokine ligand 10)/IP-10, and type-I IFN levels than moderately ill children, but enhanced MUC5AC (mucin-5AC) and IL17A gene expression in nasal cells.