Expression data from two rat strains comparing naïve vs 24h picornavirus infection.

Allergic (Th2high immunophenotype) asthmatics have a heightened susceptibility to common respiratory viral infections such as human rhinovirus. Evidence suggests that the innate interferon response is deficient in asthmatic/atopic individuals, whilst other studies show no differences in antiviral response pathways. Unsensitized and OVA-sensitized/challenged Th2high (BN rats) and Th2low immunophenotype (PVG rats) animals were inoculated intranasally with attenuated mengovirus (vMC0). Sensitized animals were exposed/unexposed during the acute viral response phase. Cellular and transcriptomic profiling was performed on bronchoalveolar lavage cells. In unsensitized PVG rats, vMC0 elicits a prototypical antiviral response (neutrophilic airways inflammation, upregulation of Th1/type I interferon-related pathways). In contrast, response to infection in the Th2high BN rats was associated with a radically altered intrinsic host response to respiratory viral infection, characterized by macrophage influx/Th2-associated pathways. In sensitized animals, response to virus infection alone was not altered compared to unsensitized animals. However, allergen exposure of sensitized animals during viral infection unleashes a notably exaggerated airways inflammatory response profile orders of magnitude higher in BN versus PVG rats despite similar viral loads. The coexposure responses in the Th2high BN incorporated type I interferon/Th1, alternative macrophage activation/Th2 and Th17 signatures. Similar factors may underlie the hyper-susceptibility to infection-associated airways inflammation characteristic of the human Th2high immunophenotype.表现为Th2高表型（Th2high immunophenotype）的变应性哮喘患者，对人鼻病毒（human rhinovirus）这类常见呼吸道病毒感染具有更高的易感性。已有研究表明，哮喘/特应性个体的先天干扰素应答（innate interferon response）存在缺陷，但也有其他研究显示抗病毒应答通路并无差异。研究人员将未经致敏、经卵清蛋白（OVA）致敏/攻击的Th2高表型BN大鼠，以及Th2低表型（Th2low immunophenotype）PVG大鼠，经鼻内接种减毒脑心肌炎病毒（vMC0）。致敏大鼠在急性病毒应答阶段分别接受或不接受过敏原暴露。对支气管肺泡灌洗液细胞（bronchoalveolar lavage cells）开展了细胞与转录组学分析。在未经致敏的PVG大鼠中，vMC0可引发典型的抗病毒应答，即中性粒细胞性气道炎症、Th1/Ⅰ型干扰素相关通路上调。与之相反，Th2高表型BN大鼠对感染的应答则出现了呼吸道病毒感染宿主固有应答的显著改变，以巨噬细胞浸润/Th2相关通路为特征。在致敏大鼠中，仅病毒感染的应答与未经致敏大鼠并无差异。然而，在病毒感染期间对致敏大鼠施加过敏原暴露后，BN大鼠的气道炎症反应谱出现显著过度的情况，尽管二者病毒载量相似，但BN大鼠的炎症反应程度较PVG大鼠高出数个数量级。Th2高表型BN大鼠的联合暴露应答包含了Ⅰ型干扰素/Th1、巨噬细胞替代激活/Th2及Th17特征通路。类似的机制或可成为人类Th2高表型（Th2high immunophenotype）人群出现感染相关气道炎症高易感性特征的基础。