Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.
Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages.
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通过支气管肺泡灌洗液的先天性和适应性免疫单细胞分析区分轻度和危重COVID-19。
DOI：
10.1038/s41422-020-00455-9
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发表时间：
2021-03
期刊：
影响因子：
44.1
通讯作者：
Lambrechts D
中科院分区：
文献类型：
--
作者：
Wauters E;Van Mol P;Garg AD;Jansen S;Van Herck Y;Vanderbeke L;Bassez A;Boeckx B;Malengier-Devlies B;Timmerman A;Van Brussel T;Van Buyten T;Schepers R;Heylen E;Dauwe D;Dooms C;Gunst J;Hermans G;Meersseman P;Testelmans D;Yserbyt J;Tejpar S;De Wever W;Matthys P;CONTAGIOUS collaborators;Neyts J;Wauters J;Qian J;Lambrechts D
先天性和获得性宿主免疫系统如何错误地沟通从而恶化新冠肺炎的免疫病理还没有完全阐明。在这里，我们对5例轻症和26例重症新冠肺炎患者的支气管肺泡灌洗标本进行了单细胞深度免疫分析，并与非新冠肺炎肺炎和正常肺的BAL进行了比较。我们使用伪时间推断来建立T细胞和单核细胞到巨噬细胞的轨迹，并模拟沿着它们的基因表达变化。在轻度新冠肺炎中，CD8+驻留记忆(TRM)和CD 4+T辅助17(TH17)细胞在接近运动轨迹结束时经历活跃的(推测是由抗原驱动的)扩增，并且具有良好的效应功能，而在重症新冠肺炎中，它们仍然保持着更天真的状态。相反，具有T辅助-1特征的CD_4+T细胞(类TH1样)和表达衰竭标志物的CD_8+T细胞(类TeX样)在轻度新冠肺炎的轨迹中途浓缩，在那里它们也表现出良好的效应功能，而在临界新冠肺炎中，它们在轨迹的末端显示出炎症相关应激的证据。单核细胞到巨噬细胞的运动轨迹显示，慢性炎症性单核细胞在关键的新冠肺炎中丰富，而以抗炎和抗原呈递特性为特征的肺泡巨噬细胞则被耗尽。在重症新冠肺炎中，单核细胞参与了三磷酸腺苷-嘌呤能信号-炎症体足迹，可能导致新冠肺炎相关的纤维化和疾病严重程度的恶化。最后，病毒RNA追踪揭示了被感染的肺上皮细胞，以及参与病毒清除的相当大比例的中性粒细胞和巨噬细胞。
How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild and 26 with critical COVID-19 in comparison to BALs from non-COVID-19 pneumonia and normal lung. We use pseudotime inference to build T-cell and monocyte-to-macrophage trajectories and model gene expression changes along them. In mild COVID-19, CD8+ resident-memory (TRM) and CD4+ T-helper-17 (TH17) cells undergo active (presumably antigen-driven) expansion towards the end of the trajectory, and are characterized by good effector functions, while in critical COVID-19 they remain more naïve. Vice versa, CD4+ T-cells with T-helper-1 characteristics (TH1-like) and CD8+ T-cells expressing exhaustion markers (TEX-like) are enriched halfway their trajectories in mild COVID-19, where they also exhibit good effector functions, while in critical COVID-19 they show evidence of inflammation-associated stress at the end of their trajectories. Monocyte-to-macrophage trajectories show that chronic hyperinflammatory monocytes are enriched in critical COVID-19, while alveolar macrophages, otherwise characterized by anti-inflammatory and antigen-presenting characteristics, are depleted. In critical COVID-19, monocytes contribute to an ATP-purinergic signaling-inflammasome footprint that could enable COVID-19 associated fibrosis and worsen disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, and a significant proportion of neutrophils and macrophages that are involved in viral clearance.
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