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Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

ABSTRACT: The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NF?B) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.

SUBMITTER: Zhu L

PROVIDER: S-EPMC7368915 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

Zhu Linnan L Yang Penghui P Zhao Yingze Y Zhuang Zhenkun Z Wang Zhifeng Z Song Rui R Zhang Jie J Liu Chuanyu C Gao Qianqian Q Xu Qumiao Q Wei Xiaoyu X Sun Hai-Xi HX Ye Beiwei B Wu Yanan Y Zhang Ning N Lei Guanglin G Yu Lingxiang L Yan Jin J Diao Guanghao G Meng Fanping F Bai Changqing C Mao Panyong P Yu Yeya Y Wang Mingyue M Yuan Yue Y Deng Qiuting Q Li Ziyi Z Huang Yunting Y Hu Guohai G Liu Yang Y Wang Xiaoqian X Xu Ziqian Z Liu Peipei P Bi Yuhai Y Shi Yi Y Zhang Shaogeng S Chen Zhihai Z Wang Jian J Xu Xun X Wu Guizhen G Wang Fu-Sheng FS Gao George F GF Liu Longqi L Liu William J WJ

Immunity 20200719 3

The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis ...[more]

PMID: 32783921

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Project description:BackgroundAcute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive.MethodsTen AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells.ResultsWe identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell-cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture.ConclusionsOur studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.

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Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

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Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

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