一种类型的干扰素在肝硬化中形成腹免疫力,并在感染时驱动卡斯帕-5介导的前列腺素释放
Michael Rooney1, Shivalee N Duduskar2, Mohamed Ghait2
1Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Jena, Germany; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
Journal of hepatology
|June 27, 2024
概括
在肝硬化患者中产生I型干扰素 (IFN).
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 微生物学 微生物学
背景情况:
- 肠道细菌转移有助于免疫功能障碍和肝硬化中的自发性细菌性腹膜炎 (SBP).
- 腹巨细胞 (PMs) 在腹腔内的免疫反应中起着关键作用.
研究的目的:
- 调查细菌DNA暴露在刺激腹膜巨细胞 (PMs) I型干扰素 (IFN) 生产中的作用.
- 了解I型IFN如何影响炎症酶激活,损伤相关分子模式 (DAMP) 释放和肝硬化中的免疫反应.
- 在SBP中探索血清progranulin和患者存活率之间的联系.
主要方法:
- 在肝硬化患者中刺激细菌DNA (大肠杆菌ssDNA),脂多糖和IFN或体外细菌感染的PM.
- 使用qPCR,ELISA,西部斑点和记者细胞量化细胞因子释放,炎细胞激活和DAMP释放.
- 血清progranulin与SBP患者的无移植生存率的相关性.
主要成果:
- 大肠杆菌ssDNA诱导了PM和单细胞中的I型IFN活性,增强了随后的炎症反应.
- 在细菌感染期间的I型IFN释放与上调的IFN调节因子 (IRF) 和酸结合蛋白 (GBP) 相关联.
- 在细菌感染期间,progranulin释放依赖于caspase-11和gasdermin D,由I型IFN和caspase-5调节.
- 在SBP患者中,较高的血清progranulin水平与较低的90天无移植生存率有关.
结论:
- 第一种类型的IFN在塑造关节细胞硬化中的免疫反应中起着至关重要的作用.
- 一种类型的IFN调节SBP期间从巨细胞中释放的卡斯帕-5介导的益格拉努林.
- 普罗格拉努林可以作为炎症酶激活和SBP的预后的生物标志物.
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