Table_1_Atopy-Dependent and Independent Immune Responses in the Heightened Severity of Atopics to Respiratory Viral Infections: Rat Model Studies.xlsx

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, while 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 co-exposure 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，对人鼻病毒等常见呼吸道病毒感染的易感性显著升高。现有研究证据显示，哮喘或特应性个体的先天性干扰素应答存在缺陷，但亦有研究表明其抗病毒应答通路并无显著差异。研究人员将未致敏、经卵清蛋白（OVA）致敏/激发的Th2高表型（Th2high immunophenotype，BN大鼠）及Th2低表型（Th2low immunophenotype，PVG大鼠）实验动物，经鼻内接种减毒门戈病毒（vMC0）。致敏组动物在急性病毒感染应答阶段，分别接受过敏原暴露或不暴露处理。研究人员对支气管肺泡灌洗细胞开展了细胞与转录组谱分析。在未致敏的PVG大鼠中，vMC0可诱导典型的抗病毒应答，表现为中性粒细胞性气道炎症及Th1/Ⅰ型干扰素相关通路的上调。与之相反，Th2高表型BN大鼠的感染应答则呈现出宿主呼吸道病毒感染固有应答的显著重塑，其特征为巨噬细胞募集与Th2相关通路的激活。在致敏动物中，仅病毒感染所引发的应答与未致敏动物相比无显著差异。然而，若在病毒感染期间对致敏动物施加过敏原暴露，则会触发显著过度的气道炎症应答特征谱：尽管两组动物的病毒载量无明显差异，但BN大鼠的炎症程度较PVG大鼠高出数个数量级。Th2高表型BN大鼠的共暴露应答涵盖了Ⅰ型干扰素/Th1、替代性巨噬细胞活化/Th2以及Th17特征谱。上述类似机制或可解释人类Th2高表型个体所特有的感染相关气道炎症易感性增高现象。