哮喘患者中气道上皮细胞对RSV的反应主要表现为粘液细胞和多纤毛细胞的受损
2024/02/23
摘要
背景：在哮喘患者中，呼吸道合胞体病毒（RSV）感染可能通过感染气道上皮层并诱导随后的免疫反应来引起疾病恶化。在大多数研究中发现，哮喘患者上皮细胞对RSV感染的I型干扰素抗病毒反应存在减弱，但并非所有研究都得出了这一结论。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明确。
方法：本文中，我们调查了来自哮喘患者（n=8）和健康供体（n=8）的原代支气管上皮细胞（pBECs）对RSV感染的转录反应。从支气管刷取的pBECs在空气液界面条件下分化，并感染RSV。3天后，细胞被处理进行单细胞RNA测序。
结果：所有样本中的所有细胞类型均对RSV显示出强烈的抗病毒反应（p<1e-48）。在RSV感染后，大多数（1045）不同调节的基因在转变为分泌细胞的细胞中被发现。哮喘患者的粘液细胞显示出较低的干扰素反应相关基因的表达（假发现率<0.05），包括OASL、ICAM1和TNFAIP3。在多纤毛细胞中观察到哮喘中与RSV反应相关的信号通路的损伤。
结论：我们的结果突出显示，在哮喘和健康气道中，支气管上皮对RSV感染的反应在很大程度上是相似的。然而，在哮喘中，粘液细胞和多纤毛细胞的反应受到损害，突显了在哮喘发作的情况下需要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
Aurore C A Gay, Martin Banchero, Orestes Carpaij, Tessa M Kole, Leonie Apperloo, Djoke van Gosliga, Putri Ayu Fajar, Gerard H Koppelman, Louis Bont, Rudi W Hendriks, Maarten van den Berge, Martijn C Nawijn
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 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.
背景：在哮喘患者中，呼吸道合胞体病毒（RSV）感染可能通过感染气道上皮层并诱导随后的免疫反应来引起疾病恶化。在大多数研究中发现，哮喘患者上皮细胞对RSV感染的I型干扰素抗病毒反应存在减弱，但并非所有研究都得出了这一结论。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明确。
方法：本文中，我们调查了来自哮喘患者（n=8）和健康供体（n=8）的原代支气管上皮细胞（pBECs）对RSV感染的转录反应。从支气管刷取的pBECs在空气液界面条件下分化，并感染RSV。3天后，细胞被处理进行单细胞RNA测序。
结果：所有样本中的所有细胞类型均对RSV显示出强烈的抗病毒反应（p<1e-48）。在RSV感染后，大多数（1045）不同调节的基因在转变为分泌细胞的细胞中被发现。哮喘患者的粘液细胞显示出较低的干扰素反应相关基因的表达（假发现率<0.05），包括OASL、ICAM1和TNFAIP3。在多纤毛细胞中观察到哮喘中与RSV反应相关的信号通路的损伤。
结论：我们的结果突出显示，在哮喘和健康气道中，支气管上皮对RSV感染的反应在很大程度上是相似的。然而，在哮喘中，粘液细胞和多纤毛细胞的反应受到损害，突显了在哮喘发作的情况下需要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 顾宪民 摘译 林江涛 审校)
(Thorax. 2024 Feb 19:thorax-2023-220230. doi: 10.1136/thorax-2023-220230.)
(Thorax. 2024 Feb 19:thorax-2023-220230. doi: 10.1136/thorax-2023-220230.)
Airway epithelial cell response to RSV is mostly impaired in goblet and multiciliated cells in asthma
Aurore C A Gay, Martin Banchero, Orestes Carpaij, Tessa M Kole, Leonie Apperloo, Djoke van Gosliga, Putri Ayu Fajar, Gerard H Koppelman, Louis Bont, Rudi W Hendriks, Maarten van den Berge, Martijn C Nawijn
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 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.
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