预激活时间通过STING抑制来确定流感的严重程度和病毒病原性
Tong Zhu1, Mengru Zhu1, Feiyu Lu2
1Department of Neonatology, Institute of Pediatrics, Children's Medical Center, First Hospital of Jilin University, Jilin University, Changchun, 130021, Jilin, China.
Scientific reports
|December 24, 2025
概括
细胞预刺激通过增加炎症细胞死亡,与抑制的STING激活相关,使流感的严重程度恶化. 这揭示了共感染病原发生的新型细胞内在机制.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 病毒学 病毒学
背景情况:
- 严重的流感通常涉及联合感染,但在免疫参与之前呼吸道上皮细胞内在反应尚不清楚.
- 研究了共感染中的免疫介导机制,但对流感病原发生的细胞预激活效应尚不清楚.
研究的目的:
- 为了研究呼吸道上皮细胞在预激活后的A型流感病毒 (IAV) 共感染期间的细胞内在反应.
- 阐明STING (干扰素基因刺激器) 途径和炎症细胞死亡在加剧流感严重性的作用.
主要方法:
- 在实验室模型中使用预激活的B16黑色素瘤细胞与CpG ODN,其次是IAV感染.
- 通过西部抹杀和RT-qPCR评估STING表达和激活.
- 在小鼠模型中进行了体内验证,并进行了鼻内CpG ODN预处理和IAV挑战,并补充了RNA-seq.
主要成果:
- 预激活在24小时内增强了IAV诱导的细胞死亡,独立于病毒复制或TLR9信号.
- 初始的STING激活随后抑制了STING酸化,并在IAV感染后增加了炎症细胞死亡.
- 在小鼠中进行CpG ODN预治疗导致死亡率增加和肺部损伤加重,RNA-seq表明皮रोप托斯参与.
结论:
- 细胞预刺激通过促进炎症性细胞死亡,加剧了流感的严重程度.
- 这种恶化在机制上与IAV随后抑制STING激活有关.
- 这项研究确定了一种新的细胞内在的致病机制,有助于共同感染的严重程度.
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