Background In patients with asthma, respiratory syncytial virus (RSV) infections can cause disease exacerbation by infecting the epithelial layer of the airways, inducing subsequent immune response. The type I interferon antiviral response of epithelial cells upon RSV infection is found to be reduced in asthma in most—but not all—studies. Moreover, the molecular mechanisms causing the differences in the asthmatic bronchial epithelium in response to viral infection are poorly understood. Methods Here, we investigated the transcriptional response to RSV infection of primary bronchial epithelial cells (pBECs) from patients with asthma (n=8) and healthy donors (n=8). The pBECs obtained from bronchial brushes were differentiated in air-liquid interface conditions and infected with RSV. After 3 days, cells were processed for single-cell RNA sequencing. Results A strong antiviral response to RSV was observed for all cell types, for all samples (p<1e-48). Most (1045) differentially regulated genes following RSV infection were found in cells transitioning to secretory cells. Goblet cells from patients with asthma showed lower expression of genes involved in the interferon response (false discovery rate <0.05), including OASL , ICAM1 and TNFAIP3 . In multiciliated cells, an impairment of the signalling pathways involved in the response to RSV in asthma was observed. Conclusion Our results highlight that the response to RSV infection of the bronchial epithelium in asthma and healthy airways was largely similar. However, in asthma, the response of goblet and multiciliated cells is impaired, highlighting the need for studying airway epithelial cells at high resolution in the context of asthma exacerbation. Data are available upon reasonable request. Count matrices are available on EGA. Full supplemental tables are available on .

中文翻译：

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哮喘患者的杯状细胞和多纤毛细胞中气道上皮细胞对 RSV 的反应大多受损

背景 在哮喘患者中，呼吸道合胞病毒（RSV）感染可通过感染气道上皮层并诱导随后的免疫反应而导致疾病恶化。大多数（但不是全部）研究发现，哮喘患者 RSV 感染后上皮细胞的 I 型干扰素抗病毒反应降低。此外，导致哮喘支气管上皮对病毒感染反应差异的分子机制尚不清楚。方法在这里，我们研究了哮喘患者 (n=8) 和健康供体 (n=8) 的原代支气管上皮细胞 (pBEC) 对 RSV 感染的转录反应。从支气管刷获得的 pBEC 在气液界面条件下分化并感染 RSV。3 天后，对细胞进行处理以进行单细胞 RNA 测序。结果 所有细胞类型、所有样本均观察到对 RSV 的强烈抗病毒反应 (p<1e-48)。RSV 感染后大多数 (1045) 个差异调节基因是在转变为分泌细胞的细胞中发现的。哮喘患者的杯状细胞显示干扰素反应相关基因的表达较低（错误发现率<0.05），包括 OASL 、 ICAM1 和 TNFAIP3 。在多纤毛细胞中，观察到参与哮喘 RSV 反应的信号通路受损。结论 我们的结果强调，哮喘和健康气道中支气管上皮对 RSV 感染的反应在很大程度上相似。然而，在哮喘中，杯状细胞和多纤毛细胞的反应受到损害，这凸显了在哮喘恶化的情况下以高分辨率研究气道上皮细胞的必要性。数据可根据合理要求提供。EGA 上提供了计数矩阵。完整的补充表可在。