Zhu Airu, Zhou Liang, Chen Zhao, Liu Dongdong, Feng Huijian, Cai Baomei, Chen Xinwen, Zhao Jincun, Zhao Jingxian, Chen Jiekai, Li Manshu, He Jiangping
State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China.
Department of Critical Care Medicine, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, 151 Yanjiang Street West, Guangzhou, Guangdong, 510120, China.
Heliyon. 2024 Sep 27;10(19):e38688. doi: 10.1016/j.heliyon.2024.e38688. eCollection 2024 Oct 15.
The vastly spreading COVID-19 pneumonia is caused by SARS-CoV-2. Lymphopenia and cytokine levels are tightly associated with disease severity. However, virus-induced immune dysregulation at cellular and molecular levels remains largely undefined. Here, the leukocytes in the pleural effusion, sputum, and peripheral blood biopsies from severe and mild patients were analyzed at single-cell resolution. Drastic T cell hyperactivation accompanying elevated T cell exhaustion was observed, predominantly in pleural effusion. The mechanistic investigation identified a group of CD14 monocytes and macrophages highly expressing and in the biopsies from severe patients, suggesting M2 macrophage polarization. These M2-like cells exhibited up-regulated (M-CSF), and signaling pathways. Further, cell type specific dysregulation of transposable elements was observed in Severe COVID-19 patients. Together, our results suggest that severe SARS-CoV-2 infection causes immune dysregulation by inducing M2 polarization and subsequent T cell exhaustion. This study improves our understanding of COVID-19 pathogenesis.
广泛传播的新型冠状病毒肺炎由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起。淋巴细胞减少和细胞因子水平与疾病严重程度密切相关。然而,病毒在细胞和分子水平上引起的免疫失调在很大程度上仍不明确。在此,我们以单细胞分辨率分析了重症和轻症患者胸腔积液、痰液及外周血活检组织中的白细胞。观察到T细胞显著过度活化并伴有T细胞耗竭增加,主要出现在胸腔积液中。机制研究在重症患者的活检组织中鉴定出一组高表达特定基因的CD14单核细胞和巨噬细胞,提示M2巨噬细胞极化。这些M2样细胞表现出上调的集落刺激因子1(CSF1,即M-CSF)和信号通路。此外,在重症新型冠状病毒肺炎患者中观察到转座元件的细胞类型特异性失调。总之,我们的结果表明,严重的SARS-CoV-2感染通过诱导M2极化和随后的T细胞耗竭导致免疫失调。本研究增进了我们对新型冠状病毒肺炎发病机制的理解。