皮质细胞的病毒传感涉及PKR和caspase-3依赖的气体皮质E孔的生成
Coralie Guy1, Marcin Baran1, Pau Ribó-Molina2
1School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
iScience
|September 8, 2023
概括
人类支气管上皮细胞使用气体皮质D (GSDMD) 和气体皮质E (GSDME) 毛孔对抗病毒感染. 这种气体皮质毛孔形成对抗流感等RNA病毒的先天免疫反应至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 病毒学 病毒学
背景情况:
- 髓状细胞通过炎症体感知病毒,触发细胞死亡和细胞因子释放.
- 皮质细胞病毒感应机制对抗RNA病毒的先天免疫力至关重要,仍然不太了解.
- 气体蛋白质形成毛孔,调解热和炎症性细胞因子的释放.
研究的目的:
- 为了阐明人类支气管上皮细胞中的病毒传感途径和气皮胺激活.
- 调查NLRP1,PKR和caspases在上皮细胞对病毒dsrna和A型流感病毒 (IAV) 的反应中的作用.
- 为了确定在上皮细胞中形成气体皮质孔的抗病毒功能.
主要方法:
- 用多I:C (dsRNA模仿) 和流感A病毒 (IAV) 刺激人类支气管上皮细胞.
- 对炎性酶激活,酶活性 (酶-1,-3,-8) 和气皮素D (GSDMD) 和气皮素E (GSDME) 裂变的分析.
- 在抑制GSDMD和GSDME表达时评估细胞因子释放,细胞死亡和病毒复制.
主要成果:
- 多I:C) 激活了NLRP1炎症酶和GSDMD通过caspase-1分裂.
- 涉及PKR和caspase-3的并行途径导致GSDME裂变和孔隙形成.
- IAV感染触发了GSDME激活,细胞因子释放和细胞死亡通过PKR-, caspase-8-和caspase-3依赖的途径.
- 抑制GSDMD和GSDME增强了IAV复制,表明抗病毒作用.
结论:
- 人类支气管上皮细胞在病毒感知和防御方面采用了不同的气皮胺介导途径.
- NLRP1和PKR作为关键传感器,分别调节GSDMD和GSDME的激活.
- 气体皮质孔形成是上皮细胞内固有的抗病毒机制,限制病毒复制.
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