哮喘患者气道上皮细胞对RSV的反应主要受损于杯状细胞和多纤毛细胞
2024/03/26
摘要
背景：在哮喘患者中，呼吸道合胞病毒(respiratory syncytial virus, RSV)感染可通过感染气道上皮层导致疾病加重，诱导后续免疫应答。大多数(但不是全部)研究发现哮喘患者上皮细胞在RSV感染后的I型干扰素抗病毒反应降低。此外，引起哮喘支气管上皮细胞对病毒感染反应差异的分子机制尚不清楚。
方法：在这里，我们研究了来自哮喘患者(n=8)和健康供者(n=8)的原代支气管上皮细胞(pBECs)对RSV感染的转录反应。在气液界面条件下对支气管刷取的pBECs进行分化并感染RSV。3 d后，细胞进行单细胞RNA测序。
结果：在所有细胞类型和所有样本(p＜1e-48)中均观察到对RSV的强烈抗病毒反应。RSV感染后，大部分(1045个)差异调节基因在向分泌细胞转化的细胞中被发现。哮喘患者杯状细胞中与干扰素应答相关的基因OASL、ICAM1和TNFAIP3的表达降低(错误发现率＜0.05)。在多毛细胞中，我们观察到参与哮喘患者对RSV应答的信号通路受损。
结论：我们的结果强调了哮喘和健康气道的支气管上皮对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损，这凸显了在哮喘急性发作的背景下对气道上皮细胞进行高分辨率研究的必要性。
Airway epithelial cell response to RSV is mostly impaired in goblet and multiciliated cells in asthma
A.C. A. Gay, M. Banchero, O. Carpaij, T. M. Kole, L. Apperloo, D. van Gosliga, et al.
Abstract
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 signaling pathways involved in the response to RSV in asthma was observed.
CONCLUSIONS: 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.
背景：在哮喘患者中，呼吸道合胞病毒(respiratory syncytial virus, RSV)感染可通过感染气道上皮层导致疾病加重，诱导后续免疫应答。大多数(但不是全部)研究发现哮喘患者上皮细胞在RSV感染后的I型干扰素抗病毒反应降低。此外，引起哮喘支气管上皮细胞对病毒感染反应差异的分子机制尚不清楚。
方法：在这里，我们研究了来自哮喘患者(n=8)和健康供者(n=8)的原代支气管上皮细胞(pBECs)对RSV感染的转录反应。在气液界面条件下对支气管刷取的pBECs进行分化并感染RSV。3 d后，细胞进行单细胞RNA测序。
结果：在所有细胞类型和所有样本(p＜1e-48)中均观察到对RSV的强烈抗病毒反应。RSV感染后，大部分(1045个)差异调节基因在向分泌细胞转化的细胞中被发现。哮喘患者杯状细胞中与干扰素应答相关的基因OASL、ICAM1和TNFAIP3的表达降低(错误发现率＜0.05)。在多毛细胞中，我们观察到参与哮喘患者对RSV应答的信号通路受损。
结论：我们的结果强调了哮喘和健康气道的支气管上皮对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损，这凸显了在哮喘急性发作的背景下对气道上皮细胞进行高分辨率研究的必要性。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Thorax 2024 DOI: 10.1136/thorax-2023-220230）
（Thorax 2024 DOI: 10.1136/thorax-2023-220230）
Airway epithelial cell response to RSV is mostly impaired in goblet and multiciliated cells in asthma
A.C. A. Gay, M. Banchero, O. Carpaij, T. M. Kole, L. Apperloo, D. van Gosliga, et al.
Abstract
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 signaling pathways involved in the response to RSV in asthma was observed.
CONCLUSIONS: 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.
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