Th2型炎症通过纤毛上皮细胞的功能的改变减少过敏性哮喘气道上皮中SARS-CoV-2的复制
2023/05/25
摘要
背景：众所周知，尽管过敏性哮喘患者对其他呼吸道病毒感染易感，但他们对2019年新型冠状病毒病(COVID-19)的易感性较低。
目的：我们试图通过使用来自空气过敏原致敏的哮喘儿童和健康的未致敏儿童的支气管气道上皮细胞(AECs)，确定呼吸道Th2型炎症抵抗SARS-CoV-2病毒引发的急性呼吸道综合征的机制。
方法：我们测量了SARS-CoV-2的复制和ACE2含量，并对用IL-13治疗或不治疗的SARS-CoV-2感染的AEC的离体样品进行了批量和单细胞RNA测序。
结果：我们观察到过敏性哮喘儿童AECs中的病毒复制量低于健康的未致敏儿童，IL-13治疗仅在过敏性哮喘患儿中减少了病毒复制量，而在健康儿童中未见效。较低的病毒转录水平与分化的纤毛上皮相关的功能通路下调以及纤毛和轴素的产生和功能有关，但与ACE2表达降低或杯状细胞或粘液分泌通路增加无关。此外，单细胞RNA测序鉴定了相对未分化的纤毛上皮的特定亚群(常见于过敏性哮喘和对IL-13的强响应)，这直接导致了病毒复制受损。
结论：我们的研究结果确定了过敏性哮喘患者针对SARS-CoV-2感染会产生先天保护的新机制，为正愈演愈烈的新冠疫情大流行提供了重要的分子学和临床学方面的见解。
Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells.
Doni Jayavelu N, Altman MC, Benson B
Abstrast
Background: Despite well-known susceptibilities to other respiratory viral infections, individuals with allergic asthma have shown reduced susceptibility to severe coronavirus disease 2019 (COVID-19).
Objective: We sought to identify mechanisms whereby type 2 inflammation in the airway protects against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using bronchial airway epithelial cells (AECs) from aeroallergen-sensitized children with asthma and healthy nonsensitized children.
Methods: We measured SARS-CoV-2 replication and ACE2 protein and performed bulk and single-cell RNA sequencing of ex vivo infected AEC samples with SARS-CoV-2 infection and with or without IL-13 treatment.
Results: We observed that viral replication was lower in AECs from children with allergic asthma than those from in healthy nonsensitized children and that IL-13 treatment reduced viral replication only in children with allergic asthma and not in healthy children. Lower viral transcript levels were associated with a downregulation of functional pathways of the ciliated epithelium related to differentiation as well as cilia and axoneme production and function, rather than lower ACE2 expression or increases in goblet cells or mucus secretion pathways. Moreover, single-cell RNA sequencing identified specific subsets of relatively undifferentiated ciliated epithelium (which are common in allergic asthma and highly responsive to IL-13) that directly accounted for impaired viral replication.
Conclusions: Our results identify a novel mechanism of innate protection against SARS-CoV-2 in allergic asthma that provides important molecular and clinical insights during the ongoing COVID-19 pandemic.
背景：众所周知，尽管过敏性哮喘患者对其他呼吸道病毒感染易感，但他们对2019年新型冠状病毒病(COVID-19)的易感性较低。
目的：我们试图通过使用来自空气过敏原致敏的哮喘儿童和健康的未致敏儿童的支气管气道上皮细胞(AECs)，确定呼吸道Th2型炎症抵抗SARS-CoV-2病毒引发的急性呼吸道综合征的机制。
方法：我们测量了SARS-CoV-2的复制和ACE2含量，并对用IL-13治疗或不治疗的SARS-CoV-2感染的AEC的离体样品进行了批量和单细胞RNA测序。
结果：我们观察到过敏性哮喘儿童AECs中的病毒复制量低于健康的未致敏儿童，IL-13治疗仅在过敏性哮喘患儿中减少了病毒复制量，而在健康儿童中未见效。较低的病毒转录水平与分化的纤毛上皮相关的功能通路下调以及纤毛和轴素的产生和功能有关，但与ACE2表达降低或杯状细胞或粘液分泌通路增加无关。此外，单细胞RNA测序鉴定了相对未分化的纤毛上皮的特定亚群(常见于过敏性哮喘和对IL-13的强响应)，这直接导致了病毒复制受损。
结论：我们的研究结果确定了过敏性哮喘患者针对SARS-CoV-2感染会产生先天保护的新机制，为正愈演愈烈的新冠疫情大流行提供了重要的分子学和临床学方面的见解。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2023 Mar 29; doi: 10.1016/j.jaci.2023.03.021. IF: 10.228
(J Allergy Clin Immunol. 2023 Mar 29; doi: 10.1016/j.jaci.2023.03.021. IF: 10.228
Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells.
Doni Jayavelu N, Altman MC, Benson B
Abstrast
Background: Despite well-known susceptibilities to other respiratory viral infections, individuals with allergic asthma have shown reduced susceptibility to severe coronavirus disease 2019 (COVID-19).
Objective: We sought to identify mechanisms whereby type 2 inflammation in the airway protects against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using bronchial airway epithelial cells (AECs) from aeroallergen-sensitized children with asthma and healthy nonsensitized children.
Methods: We measured SARS-CoV-2 replication and ACE2 protein and performed bulk and single-cell RNA sequencing of ex vivo infected AEC samples with SARS-CoV-2 infection and with or without IL-13 treatment.
Results: We observed that viral replication was lower in AECs from children with allergic asthma than those from in healthy nonsensitized children and that IL-13 treatment reduced viral replication only in children with allergic asthma and not in healthy children. Lower viral transcript levels were associated with a downregulation of functional pathways of the ciliated epithelium related to differentiation as well as cilia and axoneme production and function, rather than lower ACE2 expression or increases in goblet cells or mucus secretion pathways. Moreover, single-cell RNA sequencing identified specific subsets of relatively undifferentiated ciliated epithelium (which are common in allergic asthma and highly responsive to IL-13) that directly accounted for impaired viral replication.
Conclusions: Our results identify a novel mechanism of innate protection against SARS-CoV-2 in allergic asthma that provides important molecular and clinical insights during the ongoing COVID-19 pandemic.
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