TNF/IFN-γ 协同信号诱导COVID-19患者的不同细胞激活:对患者结果的影响
Lucero A Ramón-Luing1, Laura Edith Martínez-Gómez2, Carlos Martinez-Armenta2
1Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, Mexico.
International journal of molecular sciences
|February 13, 2025
概括
在COVID-19患者中,高水平的瘤坏死因子 (TNF) 和干扰因子- (IFN-γ) 与过度活跃的免疫细胞和严重疾病相关. 调节这些细胞因子可能为严重的COVID-19病例提供治疗潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 关键护理医学 关键护理医学
背景情况:
- 瘤坏死因子 (TNF) 和干扰素- (IFN-γ) 是COVID-19病理生理学中的关键的炎症性细胞因子.
- 收费类受体 (TLR) 7和8识别SARS-CoV-2,诱导TNF和IFN-γ的产生.
- 在改变TNF/IFN-γ水平和调解COVID-19严重程度方面,TLR依赖途径的确切作用尚不清楚.
研究的目的:
- 调查TNF/IFN-γ水平与COVID-19患者免疫细胞激活之间的关联.
- 阐明这些细胞因子水平在确定COVID-19疾病严重程度方面的作用.
主要方法:
- 150名COVID-19患者根据系统TNF和IFN-γ水平 (高与正常低) 进行分类.
- 分析了免疫细胞激活标记物,包括细胞因子概况和受体表达 (TNFR1).
- 基因变异 (SNP rs3853839) 和信号通路分子 (MYD88,NFκB,IRF7,FADD,TRADD) 被评估与TLR和TNFR1信号相关.
主要成果:
- 与正常低组相比,高TNF和IFN-γ (TNFHIFNγH) 的患者表现出高的促炎细胞因子,细胞毒性分子和T细胞和单细胞上的TNFR1表达.
- 在TNFHIFNγH组显示了遗传倾向 (SNP rs3853839) 和TLR和TNFR1信号通路中的关键分子水平的增加.
- 需要侵入性机械通风的危急疾病在患有高TNF/IFN-γ水平 (TNFHIFNγH或TNFHIFNγN-L) 的患者中更为普遍.
结论:
- 提升的TNF/IFN-γ水平与免疫细胞过度活跃有关,而正常/低水平与COVID-19中的低活性相关.
- 关键的COVID-19病理生理学可能涉及不同的途径,由不同的TNF和IFN-γ水平调节.
- 准TNF和IFN-γ调节是一个潜在的治疗策略,用于严重的COVID-19.
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