The S1 spike protein of SARS-CoV-2 upregulates the ERK/MAPK signaling pathway in DC-SIGN-expressing THP-1 cells

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
Emma Lee Johnson , Yuki Ohkawa , Noriko Kanto , Reiko Fujinawa , Taiki Kuribara , Eiji Miyoshi , Naoyuki Taniguchi
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引用次数: 0

Abstract

Dendritic cells, macrophages, neutrophils, and other antigen-presenting cells express various C-type lectin receptors that function to recognize the glycans associated with pathogens. The dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) binds various pathogens such as HIV glycoprotein 120, the Ebola glycoprotein, hemagglutinin, and the dengue virus glycoprotein in addition to the SARS-CoV-2 spike protein, and also triggers antigen-presenting cell endocytosis and immune escape from systemic infections. Many studies on the binding of SARS-CoV-2 spike protein with glycans have been published, but the underlying mechanism by which intracellular signaling occurs remains unclear. In this study, we report that the S1 spike protein of SARS-CoV-2 induces the phosphorylation of extracellular signal-regulated kinases (ERKs) in THP-1 cells, a DC-SIGN-expressing human monocytic leukemic cell line. On the other hand, the phosphorylation level of NF-κB remained unchanged under the same conditions. These data suggest that the major cell signaling pathway regulated by the S1 spike protein is the ERK pathway, which is superior to the NF-κB pathway in these DC-SIGN-expressing THP-1 cells and may contribute to immune hyperactivation in SARS-CoV-2 infections. Additionally, several glycans such as mannans, mannosylated bovine serum albumin, the serum amyloid beta protein, and intracellular adhesion molecule 3 suppressed ERK phosphorylation, suggesting that these molecules are target molecules for SARS-CoV-2 infection by suppressing immune hyperactivation that occurs in the ERK signaling pathway.

SARS-CoV-2 的 S1 尖峰蛋白能上调表达 DC-SIGN 的 THP-1 细胞的 ERK/MAPK 信号通路。
树突状细胞、巨噬细胞、嗜中性粒细胞和其他抗原递呈细胞表达各种 C 型凝集素受体,这些受体具有识别与病原体相关的聚糖的功能。DC-SIGN(树突状细胞特异性细胞间粘附分子-3-抓取非整合素)可结合多种病原体,如艾滋病毒 gp120、埃博拉病毒糖蛋白、血凝素、登革热病毒糖蛋白,此外还可结合 SARS-CoV-2 Spike 蛋白,还可引发抗原呈递细胞内吞和免疫逃逸系统性感染。关于 SARS-CoV-2 穗状病毒蛋白与聚糖结合的研究已经发表了很多,但细胞内信号转导的基本机制仍不清楚。在这项研究中,我们报告了 SARS-CoV-2 的 S1 穗状病毒蛋白在表达 DC-SIGN 的人类单核细胞白血病细胞系 THP-1 细胞中诱导 ERKs 磷酸化。另一方面,在相同条件下,NF-κB 的磷酸化水平保持不变。这些数据表明,S1尖峰蛋白调控的主要细胞信号通路是ERK通路,在这些表达DC-SIGN的THP-1细胞中,ERK通路优于NF-κB通路,并可能导致SARS-CoV-2感染中的免疫过度激活。此外,甘露聚糖、甘露聚糖化 BSA、血清淀粉样 beta 蛋白和 ICAM3 等几种聚糖抑制了 ERK 磷酸化,这表明这些分子是 SARS-CoV-2 感染的靶分子,它们抑制了 ERK 信号通路中发生的免疫过度激活。
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来源期刊
Cell Stress & Chaperones
Cell Stress & Chaperones 生物-细胞生物学
CiteScore
7.60
自引率
2.60%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Cell Stress and Chaperones is an integrative journal that bridges the gap between laboratory model systems and natural populations. The journal captures the eclectic spirit of the cellular stress response field in a single, concentrated source of current information. Major emphasis is placed on the effects of climate change on individual species in the natural environment and their capacity to adapt. This emphasis expands our focus on stress biology and medicine by linking climate change effects to research on cellular stress responses of animals, micro-organisms and plants.
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