严重急性呼吸综合征冠状病毒2感染人肺气液界面培养物显示基底细胞为相关靶标。
SARS-CoV-2 Infection of Human Lung Air-Liquid Interface Cultures Reveals Basal Cells as Relevant Targets.
作者信息
Baumgardt Morris, Obermayer Benedikt, Balázs Anita, Löwa Anna, Wyler Emanuel, Teixeira Alves Luiz Gustavo, Hellwig Katharina, Beule Dieter, Landthaler Markus, Müller Marcel A, Drosten Christian, Mall Marcus A, Hippenstiel Stefan, Hönzke Katja, Hocke Andreas C
机构信息
Department of Infectious Diseases, Respiratory Medicine, and Critical Care, Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Core Unit Bioinformatics, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
出版信息
J Infect Dis. 2025 Jun 2;231(5):1210-1220. doi: 10.1093/infdis/jiaf125.
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets ciliated cells during the initial infection of the upper respiratory tract. However, uncertainties persist regarding other involved epithelial cell types.
METHODS
We here utilized viral replication analysis, single-cell RNA sequencing, and spectral microscopy on infected air-liquid interface cultures of human primary nasal and bronchial epithelial cells to discern cell type proportions in relation to SARS-CoV-2 tropism and immune activation.
RESULTS
We revealed that, next to ciliated and secretory cells, SARS-CoV-2 (wild type and lineage B1.1.7 [Alpha variant]) strongly infects basal cells, significantly contributing to the epithelial immune response in a donor-specific manner. Moreover, local Camostat mesylate treatment was effective in both the basal and apical cell compartment, resulting in a notable reduction in viral load and reduced immune activation.
CONCLUSIONS
Collectively, our data emphasize the critical role of basal cells in facilitating SARS-CoV-2 dissemination within the upper respiratory tract and their substantial contribution to the epithelial immune response. Furthermore, our results highlight the potential of local application of Camostat mesylate as an effective strategy for inhibiting SARS-CoV-2 infection and mitigating associated immune activation early on.
背景
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在上呼吸道初始感染期间主要靶向纤毛细胞。然而，关于其他涉及的上皮细胞类型仍存在不确定性。
方法
我们在此利用病毒复制分析、单细胞RNA测序和光谱显微镜技术，对人原代鼻和支气管上皮细胞的感染气液界面培养物进行研究，以确定与SARS-CoV-2嗜性和免疫激活相关的细胞类型比例。
结果
我们发现，除了纤毛细胞和分泌细胞外，SARS-CoV-2（野生型和B1.1.7谱系[α变体]）还强烈感染基底细胞，以供体特异性方式显著促进上皮免疫反应。此外，局部甲磺酸卡莫司他治疗在基底细胞和顶端细胞区均有效，导致病毒载量显著降低和免疫激活减少。
结论
总体而言，我们的数据强调了基底细胞在促进SARS-CoV-2在上呼吸道内传播及其对上皮免疫反应的重大贡献中的关键作用。此外，我们的结果突出了局部应用甲磺酸卡莫司他作为早期抑制SARS-CoV-2感染和减轻相关免疫激活的有效策略的潜力。
Zotero 插件