在怀孕期间,A型流感病毒以剂量和时间依赖的方式破坏母亲的肠道免疫力和胎儿皮层发育
Ashley M Otero1, Meghan G Connolly1, Rafael J Gonzalez-Ricon1
1Neuroscience Program, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Molecular psychiatry
|July 3, 2024
概括
怀孕期间的病毒感染,如流感A型病毒 (IAV),可能会影响胎儿的大脑发育. 这项研究表明,感染的严重程度会影响母亲的炎症和子女的神经发育障碍的风险.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 发展生物学 发展生物学
背景情况:
- 怀孕期间母亲免疫激活 (MIA) 与后代神经发育障碍 (NDD) 有关.
- 之前的模型使用病毒模拟物,显示T辅助17 (TH17) 细胞激活和IL-17生产有助于胎儿大脑异常.
- 活病毒感染和胎儿大脑寄存巨细胞在MIA中的作用不太清楚.
研究的目的:
- 调查怀孕期间活体流感A病毒 (IAV) 感染对母亲免疫反应和胎儿大脑发育的影响.
- 为了比较活病毒模型和病毒模拟模型之间的MIA特征.
- 为了确定NDD相关结果的潜在感染严重程度值.
主要方法:
- 怀孕的小鼠被接种了两剂IAV.
- 评估了母亲的肠道和全身免疫反应.
- 评估了胎儿大脑发育,包括皮质异常和巨细胞群 (微细胞,BAMs).
- 分析了基因表达和细胞增殖标记.
主要成果:
- IAV感染导致了剂量依赖的母体结肠变化和微生物失调,但没有增加肠道TH17细胞或IL-17.
- 系统性炎症标志物 (IL-6,IFN-γ) 随着剂量和时间的不同而增加.
- 胎儿皮层异常和大脑基因表达的改变仅在高IAV剂量时才发生.
- 胎儿微质细胞数量没有变化,但脑膜BAM和大脑居民巨细胞中的CD68表达显示出剂量和时间依赖的变化.
结论:
- 怀孕期间的活体IAV感染可以诱导MIA并影响胎儿大脑发育,但特定的途径 (例如,肠道TH17/IL-17) 可能与模仿模型不同.
- 对于母体炎症和胎儿皮质异常,存在感染严重程度值.
- 活病毒模型对于充分评估NDD病原和临床转化中的免疫反应至关重要.
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