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卡介苗调节人类巨噬细胞和树突状细胞对严重急性呼吸综合征冠状病毒2刺突糖蛋白的反应。

Bacille-Calmette-Guerin modulates human macrophage and dendritic cell response to SARS-CoV-2 S-glycoprotein.

作者信息

Ambe Regina C, Bhalla Shubhang, Alvarado Alejandra, Barragan Jose, Cervantes Jorge

机构信息

Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.

Dr Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

出版信息

Infect Med (Beijing). 2023 Sep 4;2(3):241-245. doi: 10.1016/j.imj.2023.08.004. eCollection 2023 Sep.

Abstract

BACKGROUND

Given that epidemiological evidence suggests a potential protective role for Bacille-Calmette-Guerin against COVID-19, we aimed to explore whether pre-exposure of human monocyte-derived macrophages and dendritic cells to BCG could modulate their response to SARS-CoV-2 S-glycoprotein.

METHODS

Dual THP-1 cells containing 2 reporter plasmids for transcription factors NF-κB, and IRF were differentiated into macrophages over 3 days using phorbol 12-myristate 13-acetate, or into dendritic cells over 6 days using commercial monocyte-dencritic cell differentiation media and matured with recombinant tumor necrosis factor-α. Cells were exposed to BCG for 24 h and then stimulated with SARS-CoV-2 S-glycoprotein for 24 hours.

RESULTS

Pre-exposure of human macrophages and DCs to BCG increased IRF and NF-kb activation in response to the SARS-CoV-2 S-glycoprotein.

CONCLUSIONS

Our results showed that pre-exposure of both types of cells to BCG exhibited an increase in inflammatory transcription factors upon stimulation with S-glycoprotein. BCG-induced trained immunity may be an important tool for reducing susceptibility to SARS-CoV-2 infection and severity of COVID-19. Our findings help in the design of future BCG-based therapeutic approaches in the treatment of diseases caused by viral infections.

摘要

背景

鉴于流行病学证据表明卡介苗对2019冠状病毒病具有潜在保护作用,我们旨在探讨人单核细胞衍生的巨噬细胞和树突状细胞预先接触卡介苗是否会调节它们对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)刺突糖蛋白的反应。

方法

使用佛波醇12-肉豆蔻酸酯13-乙酸酯将含有转录因子核因子κB(NF-κB)和干扰素调节因子(IRF)的2种报告质粒的双THP-1细胞在3天内分化为巨噬细胞,或使用市售单核细胞-树突状细胞分化培养基在6天内分化为树突状细胞,并用重组肿瘤坏死因子-α使其成熟。细胞接触卡介苗24小时,然后用SARS-CoV-2刺突糖蛋白刺激24小时。

结果

人巨噬细胞和树突状细胞预先接触卡介苗可增加对SARS-CoV-2刺突糖蛋白反应时IRF和NF-κB的激活。

结论

我们的结果表明,两种类型的细胞预先接触卡介苗后,在用刺突糖蛋白刺激时炎症转录因子增加。卡介苗诱导的训练免疫可能是降低对SARS-CoV-2感染的易感性和2019冠状病毒病严重程度的重要工具。我们的发现有助于设计未来基于卡介苗的治疗方法来治疗由病毒感染引起的疾病。

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