在流感A病毒感染后,免疫检查点在怀孕期间被抑制
Rebecca L Vanders1, Henry M Gomez1, Katie Daly1
1Immune Health, Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia.
American journal of physiology. Lung cellular and molecular physiology
|September 10, 2024
概括
在怀孕期间感染A型流感病毒会通过增加免疫检查点蛋白质使结果变得更糟. 通过抗PDL1疗法阻断编程死亡配体-1 (PDL1),改善了母亲的免疫反应,并降低了病毒载量.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 孕产妇和胎儿医学 孕产妇和胎儿医学
背景情况:
- 流感A病毒 (IAV) 在怀孕期间带来重大风险,由怀孕引起的免疫变化加剧.
- 免疫检查点蛋白 (ICPs),包括PDL1,PD1和CTLA4,在怀孕期间被上调,可能会损害抗病毒免疫力.
- 目前的治疗方法不足以完全控制孕妇的IAV,特别是在流行病期间.
研究的目的:
- 调查ICP在怀孕期间IAV感染中的作用.
- 确定阻断PDL1在先天性免疫细胞上的表达是否可以改善母体免疫反应和IAV感染后的疾病结果.
主要方法:
- 在怀孕和非怀孕的小鼠中使用IAV感染的小鼠模型.
- 使用针对PDL1 (抗PDL1) 的免疫检查点抑制剂 (ICI) 进行治疗.
- 分析包括流细胞计,肺mRNA和炎症/抗病毒标记物的蛋白质表达,病毒标位和肺功能评估.
主要成果:
- 在怀孕的小鼠中,IAV感染导致ICP增加 (PDL1,PD1,CTLA4).
- 抗PDL1治疗抑制了ICPs,增强了免疫细胞激活 (CD86),降低了病毒标位,并减少了肺炎.
- 在抗PDL1治疗后,母亲的肺功能得到改善.
结论:
- 怀孕期间的IAV感染会激活抑制性ICP,导致更严重的疾病.
- 用抗PDL1疗法向PDL1是一种有希望的策略,可以恢复母亲的免疫功能,并减轻怀孕期间IAV的严重程度.
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