背景:由SARS-CoV-2感染引起的2019年冠状病毒病(COVID-19)的爆发已成为全球卫生紧急情况。我们的目标是破译SARS-CoV-2感染的细胞类型,COVID-19患者肺部随之而来的宿主免疫反应及其相互作用。
方法:我们分析了来自10名健康供体的支气管肺泡灌洗液(BALF)样本的单细胞RNA测序(scRNA-seq)数据,6例重症COVID-19患者和3例轻度康复患者。检测了SARS-CoV-2受体(ACE2和TMPRSS2)在不同细胞类型中的表达。免疫细胞浸润模式,他们的表情轮廓,进一步研究了免疫细胞与SARS-CoV-2靶细胞之间的相互作用。
结果:与健康对照组相比,COVID-19患者肺上皮细胞中ACE2和TMPRSS2表达明显增高,特别是俱乐部和纤毛细胞。SARS-CoV-2激活了这些细胞中的促炎基因和干扰素/细胞因子信号传导。在严重的COVID-19患者中,中性粒细胞明显升高,但是与健康对照组和轻度患者相比,观察到肺中巨噬细胞较低,细胞因子表达显着增加。相比之下,中性粒细胞和巨噬细胞恢复正常水平,而在轻度患者中观察到更多的T细胞和NK细胞积累.此外,SARS-CoV-2感染改变了肺上皮细胞和免疫细胞的社区相互作用:与健康供体相比,COVID-19患者的俱乐部和免疫细胞之间的相互作用更高;另一方面,免疫-免疫细胞相互作用在轻度患者中表现最强.
结论:SARS-CoV-2可感染肺上皮,改变肺上皮细胞和免疫系统之间的通讯模式,并驱动COVID-19患者的宿主免疫反应失调。
背景:该项目得到了中国国家重点研发计划的支持(编号:2018YFC1315000/2018YFC1315004),深圳市科技计划资助项目(JCYJ20170413161534162),HMRFHongKong(17160862),RGC-CRF香港(C4039-19G),RGC-GRF香港(14163817),副校长全权委托基金中大和中大直接拨款,深圳虚拟大学园支援中大深圳研究院计划。
BACKGROUND: The outbreak of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global health emergency. We aim to decipher SARS-CoV-2 infected cell types, the consequent host immune response and their interplay in lung of COVID-19 patients.
METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data of bronchoalveolar lavage fluid (BALF) samples from 10 healthy donors, 6 severe COVID-19 patients and 3 mild recovered patients. The expressions of SARS-CoV-2 receptors (ACE2 and TMPRSS2) were examined among different cell types. The immune cells infiltration patterns, their expression profiles, and interplays between immune cells and SARS-CoV-2 target cells were further investigated.
RESULTS: Compared to healthy controls, ACE2 and TMPRSS2 expressions were significantly higher in lung epithelial cells of COVID-19 patients, in particular club and ciliated cells. SARS-CoV-2 activated pro-inflammatory genes and interferon/cytokine signaling in these cells. In severe COVID-19 patients, significantly higher neutrophil, but lower macrophage in lung was observed along with markedly increased cytokines expression compared with healthy controls and mild patients. By contrast, neutrophil and macrophage returned to normal level whilst more T and NK cells accumulation were observed in mild patients. Moreover, SARS-CoV-2 infection altered the community interplays of lung epithelial and immune cells: interactions between the club and immune cells were higher in COVID-19 patients compared to healthy donors; on the other hand, immune-immune cells interactions appeared the strongest in mild patients.
CONCLUSIONS: SARS-CoV-2 could infect lung epithelium, alter communication patterns between lung epithelial cells and immune system, and drive dysregulated host immune response in COVID-19 patients.
BACKGROUND: This project was supported by National Key R&D Program of China (No. 2018YFC1315000/2018YFC1315004), Science and Technology Program Grant Shenzhen (JCYJ20170413161534162), HMRF Hong Kong (17160862), RGC-CRF Hong Kong (C4039-19G), RGC-GRF Hong Kong (14163817), Vice-Chancellor\'s Discretionary Fund CUHK and CUHK direct grant, Shenzhen Virtual University Park Support Scheme to CUHK Shenzhen Research Institute.