在COVID-19中,白素27的抗病毒反应和免疫病原发生
Juan Felipe Valdés-López1, Silvio Urcuqui-Inchima2
1Grupo Inmunovirología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Archives of virology
|June 13, 2023
概括
互白素27 (IL27) 在COVID-19患者中引发了独立于干扰素的强有力的抗病毒反应. 这种细胞因子激活免疫细胞,表明严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 感染的潜在新疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 感染导致严重的COVID-19,通常与细胞因子风暴和干扰素 (IFN) 介导的抗病毒防御功能受损有关.
- 最近已经证明,具有双重作用的细胞因子 - - 干白素27 (IL27) 可以独立于IFN诱导抗病毒反应.
- 了解IL27在COVID-19病变发生过程中的作用对于开发有效治疗方法至关重要.
研究的目的:
- 在COVID-19患者中调查IL27亚单元 (IL27p28和EBI3) 的转录水平.
- 阐明SARS-CoV-2感染影响IL27产生和功能的信号通路.
- 评估IL27作为针对SARS-CoV-2的治疗点的潜力.
主要方法:
- 从COVID-19患者的外周血液单核细胞 (PBMC) 和单细胞中对IL27亚单元转录的分析.
- 对托尔类受体 (TLR) 1/2-MyD88信号通路和核因子-kappa B (NF-κB) 激活的研究.
- 评估IFN调控因子1 (IRF1) 和信号转换器和转录1 (STAT1) 激活器的信号传输.
- 用SARS-CoV-2尖端蛋白刺激巨细胞.
主要成果:
- SARS-CoV-2 感染调节了 TLR1/2-MyD88 信号,激活了 NF-κB,并诱导了包括 EBI3.3 在内的促炎基因.
- 激活IRF1信号导致IL27p28mRNA表达的增加.
- 在COVID-19衍生的PBMC和单细胞中,IL27以IFN独立的方式诱导强大的STAT1依赖的炎症和抗病毒反应.
- 在用SARS-CoV-2尖端蛋白治疗的巨细胞中观察到类似的反应.
结论:
- IL27在宿主对SARS-CoV-2的抗病毒防御中发挥着重要作用,独立于IFN通路运作.
- 这些发现突显了IL27在严重的COVID-19中诱导保护性免疫反应的潜力.
- IL27代表了针对SARS-CoV-2感染的新型治疗方法的有希望的治疗候选者.
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