The S1 Subunit of the SARS-CoV-2 Spike Protein Activates Human Monocytes to Produce Cytokines Linked to COVID-19: Relevance to Galectin-3.
The S1 Subunit of the SARS-CoV-2 Spike Protein Activates Human Monocytes to Produce Cytokines Linked to COVID-19: Relevance to Galectin-3.
复制标题
DOI：
10.3389/fimmu.2022.831763
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
Bieneman AP
中科院分区：
文献类型：
--
作者：
Schroeder JT;Bieneman AP
2019 年冠状病毒病 (COVID-19) 由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起，迅速演变成一场大流行——一百年来从未经历过这样的情况。虽然新型疫苗显示出巨大的功效，并且治疗方法不断开发，但疾病的持续存在以及随之而来的新变种的威胁，继续在全世界范围内带来巨大的健康和社会经济问题。研究表明，在易感个体中，SARS-CoV-2 感染可迅速进展为肺损伤和急性呼吸窘迫综合征 (ARDS)，有证据表明潜在的先天免疫反应失调或细胞因子释放综合征 (CRS)。造成这种 CRS 的机制仍知之甚少，但 β 冠状病毒科的前身病毒，即 SARS-CoV-1 和中东呼吸综合征 (MERS)-CoV 也具有明显的高炎症特征。进一步已知，SARS-CoV-2 的刺突蛋白 (S)（首次报道其他 β 冠状病毒）在 S1 亚基 (S1-NTD) 的 N 端结构域内具有所谓的半乳糖凝集素折叠。该折叠（或口袋）显示出与人半乳糖凝集素 3 (Gal-3) 几乎相同的结构同源性。在这方面，我们最近表明，当 Gal-3 与上皮细胞结合或固定在固相基质上时，可促进先天免疫细胞的激活，包括嗜碱性粒细胞、DC 和单核细胞。这些发现的综合促使我们测试 SARS-CoV-2 刺突蛋白的片段是否也可能以类似于我们在 Gal-3 研究中观察到的方式激活先天免疫细胞。事实上，通过将 S 成分固定到微量滴定孔上，我们发现只有 S1 亚基（带有 NTD）才能激活人类单核细胞，产生与 COVID-19 相关 CRS 中报道的几乎相同的细胞因子模式。相比之下，结合 ACE2 的 S1-CTD/RBD 和 S2 亚基（茎）均未能介导相同的效果。总体而言，这些发现提供了证据，表明 SARS-CoV-2 刺突蛋白可以激活单核细胞产生 COVID-19 的核心细胞因子，从而深入了解 CRS 背后的先天免疫机制和治疗干预的潜力。
Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly evolved into a pandemic –the likes of which has not been experienced in 100 years. While novel vaccines show great efficacy, and therapeutics continue to be developed, the persistence of disease, with the concomitant threat of emergent variants, continues to impose massive health and socioeconomic issues worldwide. Studies show that in susceptible individuals, SARS-CoV-2 infection can rapidly progress toward lung injury and acute respiratory distress syndrome (ARDS), with evidence for an underlying dysregulated innate immune response or cytokine release syndrome (CRS). The mechanisms responsible for this CRS remain poorly understood, yet hyper-inflammatory features were also evident with predecessor viruses within the β-coronaviridae family, namely SARS-CoV-1 and the Middle East Respiratory Syndrome (MERS)-CoV. It is further known that the spike protein (S) of SARS-CoV-2 (as first reported for other β-coronaviruses) possesses a so-called galectin-fold within the N-terminal domain of the S1 subunit (S1-NTD). This fold (or pocket) shows structural homology nearly identical to that of human galectin-3 (Gal-3). In this respect, we have recently shown that Gal-3, when associated with epithelial cells or anchored to a solid phase matrix, facilitates the activation of innate immune cells, including basophils, DC, and monocytes. A synthesis of these findings prompted us to test whether segments of the SARS-CoV-2 spike protein might also activate innate immune cells in a manner similar to that observed in our Gal-3 studies. Indeed, by immobilizing S components onto microtiter wells, we show that only the S1 subunit (with the NTD) activates human monocytes to produce a near identical pattern of cytokines as those reported in COVID-19-related CRS. In contrast, both the S1-CTD/RBD, which binds ACE2, and the S2 subunit (stalk), failed to mediate the same effect. Overall, these findings provide evidence that the SARS-CoV-2 spike protein can activate monocytes for cytokines central to COVID-19, thus providing insight into the innate immune mechanisms underlying the CRS and the potential for therapeutic interventions.
登录
查看更多内容
DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
IP-10 和 MCP-1 作为与 COVID-19 疾病严重程度相关的生物标志物。
DOI：
10.1186/s10020-020-00230-x
发表时间：
2020-10-29
期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
--
作者：
Chen Y;Wang J;Liu C;Su L;Zhang D;Fan J;Yang Y;Xiao M;Xie J;Xu Y;Li Y;Zhang S
通讯作者：
Zhang S
影响因子：
11.1
作者：
Giamarellos-Bourboulis EJ
通讯作者：
Giamarellos-Bourboulis EJ
影响因子：
5
作者：
Behloul, Nouredine;Baha, Sarra;Meng, Jihong
通讯作者：
Meng, Jihong
影响因子：
7.3
作者：
Garcia-Revilla, Juan;Deierborg, Tomas;Boza-Serrano, Antonio
通讯作者：
Boza-Serrano, Antonio