加斯德明D在严重的流感A病毒感染期间促进高炎症和免疫病理学
Sarah Rosli1,2, Christopher M Harpur1,2, Maggie Lam1,2
1Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Vic, Australia.
Cell death & disease
|November 9, 2023
概括
加斯德明D (GSDMD) 在流感A病毒感染期间驱动严重的肺炎和损伤. 在小鼠中消除GSDMD减少了疾病严重程度和改善了生存率,强调GSDMD是致命流感结果的关键因素.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 病理学 病理学 病理学
背景情况:
- 严重的甲型流感病毒 (IAV) 感染会导致致命的肺部疾病,原因是过度炎症和组织损伤.
- 炎症性细胞死亡的Pyroptosis是由气皮素D (GSDMD) 执行的.
研究的目的:
- 调查GSDMD在促进严重IAV疾病中的作用.
- 确定GSDMD对IAV诱导的炎症和病理学的贡献.
主要方法:
- 在IAV感染的肺上皮细胞 (体外和体内) 中评估了GSDMD裂变.
- 在IAV感染后,GSDMD缺乏 (Gsdmd-/-) 和野生型小鼠的疾病严重程度,生存率和肺病理的比较.
- 量化病毒负担,中性粒细胞透,以及炎症性细胞因子和化学因子的水平.
主要成果:
- IAV感染诱导了GSDMD在肺上皮细胞的裂变.
- 与野生型小鼠相比,Gsdmd-/-小鼠的疾病严重程度降低,生存率提高,病毒载量较低.
- GSDMD缺乏症降低了中性粒细胞透和TNF,IL-6,MCP-1,IL-1α,CXCL1和CXCL2的水平,但没有IL-1β或IL-18.
- Gsdmd-/-小鼠表现出较不严重的肺病理,包括减少上皮损伤和细胞死亡.
结论:
- 在严重的IAV感染期间,GSDMD在调解炎症和组织损伤方面发挥着关键作用.
- 准GSDMD可能提供一种治疗策略,以减轻严重的流感疾病.
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