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首页> 外文期刊>Vaccine >Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses during infection of human nasal epithelial cell cultures
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Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses during infection of human nasal epithelial cell cultures

机译:在人鼻上皮细胞培养物感染期间,减毒活流感疫苗株比抗原匹配的季节性流感病毒引起更大的先天免疫应答

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Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAW virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFN beta, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33 degrees C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent clinical phenotype seen in human LAIV inoculation. (C) 2014 Elsevier Ltd. All rights reserved.
机译:流行性感冒病毒是全球性病原体,每年感染约10-20%的世界人口。疫苗,包括减毒活疫苗(LAIV),是抵抗流感感染的最佳方法。 LAIV是一种新型疫苗,可在人鼻上皮中主动复制,并引起粘膜和全身保护性免疫应答。流感季节性野生型(WT)和LAIV病毒感染人鼻上皮后,复制和先天免疫应答的差异仍然未知。使用原代分化的人鼻上皮细胞(hNECs)培养模型,我们比较了流感WT和抗原匹配的冷适应(CA)LAW病毒复制以及随后的先天免疫应答,包括宿主细胞模式识别蛋白表达,宿主先天免疫基因表达,促炎性细胞因子的分泌和细胞内病毒RNA的水平。比较WT和LAIV株之间病毒复制的生长曲线显示,与WT感染相比,LAIV期间感染性病毒的产生明显减少。尽管在传染性病毒生产中存在这种差异,LAIV株仍引起更强的先天免疫应答,其中RIG-1,TLR-3,IFNβ,STAT-1,IRF-7,MxA和IP-10的表达增加。用LDH的基底外侧水平测量,用WT和LAIV株感染的hNEC培养物之间的细胞毒性没有差异。与33℃hNEC培养液的WT病毒感染相比,LAIV期间细胞内病毒RNA的水平升高可以解释通过模式识别受体的上调和下游I型IFN表达而增强的先天免疫应答。综上所述,我们的结果表明,人鼻上皮细胞中LAIV株复制的减少与强大的先天免疫反应有关,这种免疫反应不同于季节性流感病毒的感染,限制了LAIV的脱落,并在人LAIV的无声临床表型中起作用接种。 (C)2014 Elsevier Ltd.保留所有权利。

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