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单细胞RNA测序揭示了细菌性肺炎继发脓毒症发病机制中持续存在的免疫细胞功能障碍。

Single-cell RNA sequencing reveals the sustained immune cell dysfunction in the pathogenesis of sepsis secondary to bacterial pneumonia.

作者信息

Wang Teng, Zhang Xianglong, Liu Zhanguo, Yao Tong, Zheng Dongying, Gan Jianwei, Yu Shuang, Li Lin, Chen Peng, Sun Jian

机构信息

Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.

Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China.

出版信息

Genomics. 2021 May;113(3):1219-1233. doi: 10.1016/j.ygeno.2021.01.026. Epub 2021 Mar 7.

DOI:10.1016/j.ygeno.2021.01.026
PMID:33691144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7937330/
Abstract

Sepsis is a leading cause of mortality in intensive care unit worldwide, it's accompanied by immune cell dysfunction induced by multiple factors. However, little is known about the specific alterations in immune cells in the dynamic pathogenesis of sepsis secondary to bacterial pneumonia. Here, we used single cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) in a healthy control and two patients with sepsis secondary to bacterial pneumonia, including acute, stable and recovery stage. We analyzed the quantity and function of immune cells. During disease course, interferon gamma response was upregulated; T/NK cell subtypes presented activation and exhaustion properties, which might be driven by monocytes through IL-1β signaling pathways; The proportion of plasma cells was increased, which might be driven by NK cells through IFN signaling pathways; Additionally, interferon gamma response was upregulated to a greater degree in sepsis secondary to pneumonia induced by SARS-COV-2 compared with that induced by influenza virus and bacteria.

摘要

脓毒症是全球重症监护病房中主要的死亡原因,它伴随着多种因素诱导的免疫细胞功能障碍。然而,对于细菌性肺炎继发脓毒症动态发病机制中免疫细胞的具体变化知之甚少。在此,我们使用单细胞RNA测序(scRNA-seq)对一名健康对照者以及两名细菌性肺炎继发脓毒症患者(包括急性期、稳定期和恢复期)的外周血单个核细胞(PBMC)进行分析。我们分析了免疫细胞的数量和功能。在病程中,γ干扰素反应上调;T/NK细胞亚群呈现激活和耗竭特性,这可能由单核细胞通过IL-1β信号通路驱动;浆细胞比例增加,这可能由NK细胞通过IFN信号通路驱动;此外,与流感病毒和细菌诱导的肺炎继发脓毒症相比,SARS-CoV-2诱导的肺炎继发脓毒症中γ干扰素反应上调程度更大。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/f2d6e2529ab4/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/d382078ac038/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/f3aca9770fcc/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/c9eb25fbb0e3/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/15c63ff21850/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/bd6e921050e3/gr7_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/5279711be047/mmc1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/0f5814cdaf46/mmc2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/8ca03f45fce3/mmc3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f3/7937330/49b0831a3da0/mmc4_lrg.jpg
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