流感A型感染在生理衰老过程中加速了与疾病相关的小质细胞的形成
Rogan A Grant1, Constance E Runyan1, Grace A Minogue2,3
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
bioRxiv : the preprint server for biology
|December 19, 2025
概括
流感病毒肺炎通过促进与疾病相关的微质 (DAM) 在白质中的扩张来加速大脑衰老,特别是在老年人中. 这加剧了认知能力下降的风险.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 衰老研究研究 衰老研究
背景情况:
- 严重的肺炎与认知能力下降和痴呆症有关,特别是在老年人中.
- 与疾病相关的微质细胞 (DAM) 与认知衰退和痴呆症有关.
- 甲型流感病毒 (IAV) 肺炎对大脑微质细胞的影响及其对认知衰老的贡献尚未完全理解.
研究的目的:
- 为了研究非神经侵入性流感A病毒 (IAV) 肺炎如何影响大脑微质转录反应.
- 为了确定IAV肺炎是否驱动疾病相关微质细胞 (DAM) 的过早扩张.
- 探索神经免疫群体的年龄相关变化及其对IAV感染的反应.
主要方法:
- 大量和单细胞RNA测序,代谢学和空间转录学在年轻,中年和老年雄性小鼠中使用.
- 神经免疫群体在IAV感染和恢复期间进行了分析.
- 从正常老年人,超级老年人和痴呆症患者获得的人类中额前 (MFG) 组织,并使用空间转录学分析.
主要成果:
- 在白质中观察到增加了DAM,干扰素反应微质 (IRM),CD4+和CD8+T细胞的丰度,从中年开始,在老小鼠中持续.
- DAM显示了代谢向有氧糖解转移,TCA循环中断和代谢物比率改变.
- 在中年老鼠中,IAV肺炎诱导了微质中的急性免疫衰变反应,加速了中年老鼠的DAM扩张,而老鼠显示出基线升高.
- 人类MFG分析显示,正常老年人,超级老年人和痴呆症患者的白质中类似的DAM和CD8+T细胞积累.
- 与年龄相关的DAM扩张独立于微质内在机制,这表明中枢神经系统 (CNS) 微环境的作用.
结论:
- IAV肺炎诱导了微质中的急性免疫反应.
- 这项研究加速了白质中DAM的年龄依赖扩张,将肺炎与加速的大脑衰老联系起来.
- 研究结果表明,肺炎诱导的神经炎症有助于认知能力下降的风险,特别是在老年人群中.
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