流感劫持了髓状细胞,在心脏中造成I型干扰素驱动的损伤
Jeffrey Downey1, Ana Oliveira-Coelho1, Máté G Kiss1
1Cardiovascular Research Institute and the Department of Medicine, Cardiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Immunity
|February 10, 2026
概括
流感感染通过感染携带病毒到心脏的髓状细胞来损害心脏. 阻断心脏细胞中的I型干扰素 (IFN-I) 受体可以防止这种心血管损伤.
科学领域:
- 心血管科学 心血管科学
- 传染病免疫学 传染病免疫学
- 病毒学 病毒学
背景情况:
- 流感感染与心血管疾病有关,但潜在的机制尚不清楚.
- 了解病毒感染如何影响心脏对于公共健康至关重要.
- 现有的研究缺乏关于流感心脏并发症的详细见解.
研究的目的:
- 阐明流感感染损害心脏的机制.
- 为了确定特定的细胞相互作用和分子途径参与心脏损伤后流感.
- 探索潜在的治疗点,以减轻流感引起的心血管并发症.
主要方法:
- 使用了流感感染的小鼠模型.
- 追踪肺部感染后的病毒传播和细胞热流.
- 研究了髓状亲树突细胞 (pro-DC3),化学激素受体 (CCR2,CCL2) 和I型干扰素 (IFN-I) 信号传递的作用.
- 评估心脏功能和组织损伤.
- 采用遗传和治疗策略来调节心肌细胞中的IFN-I受体 (IFNAR1) 信号传递.
主要成果:
- 据证明,流感感染会损害人类和小鼠的心脏.
- 肺性流感感染导致了循环中的表达CCR2.2.的髓状亲DC3细胞感染.
- 由于CCL2的产生,这些受感染的细胞被优先吸引到心脏.
- 病毒逃脱了心肌中的亲DC3细胞,感染了心肌细胞,并诱导了IFN-I的产生.
- IFNAR1对心肌细胞的接触导致心脏组织损伤和功能障碍.
- 专门针对心肌细胞的IFNAR1保护了心脏,而不损害肺部抗病毒免疫力.
结论:
- 流感感染通过一系列宿主-病原体相互作用传播心脏损伤.
- 受感染的髓状细胞作为载体,将病毒传递到心脏.
- 心肌细胞中的I型干扰素信号传递是心脏功能障碍的关键驱动因素.
- 针对心肌细胞中的IFNAR1轴提供了一个有希望的策略,以预防流感的心血管并发症.
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