Biochemistry Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Medical Research Core Facility and Platforms, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh 11426, Saudi Arabia.
Int J Mol Sci. 2022 Aug 4;23(15):8669. doi: 10.3390/ijms23158669.
Dysregulation of renin-angiotensin systems during coronavirus disease 2019 (COVID-19) infection worsens the symptoms and contributes to COVID-19 severity and mortality. This study sought to investigate the effect of exogenous angiotensin II (Ang-II) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cells response in recovered COVID-19 patients. Human peripheral blood mononuclear cells (PBMCs) were treated with Ang II and then stimulated with a SARS-CoV-2 peptide pool. T-cell responses were measured using flow cytometry, while enzyme-linked immunosorbent assay (ELISA) and intracellular cytokine staining (ICS) assays determined functional capability and polarization. Additionally, the relative level of protein phosphorylation was measured using a phosphokinase array. Our results showed that Ang II treatment significantly increased the magnitude of SARS-CoV-2-specific T-cell response in stimulated PBMCs with a SARS-CoV-2 peptide pool. Moreover, the phosphorylation levels of numerous proteins implicated in cardiovascular diseases, inflammation, and viral infection showed significant increases in the presence of Ang II. The mitogenic stimulation of PBMCs after Ang II and SARS-CoV-2 peptide pool stimulation showed functional polarization of T-cells toward Th1/Th17 and Th17 phenotypes, respectively. Meanwhile, ELISA showed increased productions of IL-1β and IL-6 in Ang II-stimulated PBMCs without affecting the IL-10 level. To our knowledge, this study is the first to demonstrate that Ang II exaggerates SARS-CoV-2-specific T-cells response. Therefore, during COVID-19 infection, Ang II may aggravate the inflammatory response and change the immune response toward a more inflammatory profile against SARS-CoV-2 infection.
血管紧张素系统在 2019 年冠状病毒病（COVID-19）感染期间的失调会加重症状，并导致 COVID-19 的严重程度和死亡率升高。本研究旨在探讨外源性血管紧张素 II（Ang-II）对已康复的 COVID-19 患者中严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）特异性 T 细胞反应的影响。用 Ang-II 处理人外周血单核细胞（PBMC），然后用 SARS-CoV-2 肽库刺激。使用流式细胞术测量 T 细胞反应，同时酶联免疫吸附测定（ELISA）和细胞内细胞因子染色（ICS）测定确定功能能力和极化。此外，使用磷酸激酶阵列测量蛋白质磷酸化的相对水平。我们的结果表明，Ang-II 处理可显著增加 SARS-CoV-2 肽库刺激 PBMC 中 SARS-CoV-2 特异性 T 细胞反应的幅度。此外，在存在 Ang-II 的情况下，许多与心血管疾病、炎症和病毒感染相关的蛋白质的磷酸化水平显着增加。Ang-II 和 SARS-CoV-2 肽库刺激 PBMC 后的有丝分裂刺激显示 T 细胞分别向 Th1/Th17 和 Th17 表型的功能极化。同时，ELISA 显示 Ang-II 刺激的 PBMC 中 IL-1β和 IL-6 的产生增加，而不影响 IL-10 水平。据我们所知，这项研究首次表明 Ang-II 可夸大 SARS-CoV-2 特异性 T 细胞反应。因此，在 COVID-19 感染期间，Ang-II 可能会加重炎症反应，并使针对 SARS-CoV-2 感染的免疫反应向更具炎症特征的方向转变。
