IRF8 调节NLRC4炎症酶激活的NAIPs转录
Rajendra Karki1, Ein Lee2, David Place1
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Cell
|March 27, 2018
概括
干扰素调节因子8 (IRF8) 对于对抗细菌感染的最佳NLRC4炎症酶激活至关重要. IRF8 调节NAIP,通过细胞因子产生和热死增强宿主防御.
科学领域:
- 免疫学
- 微生物学
- 细胞生物学
背景情况:
- 炎症酶激活对于对微生物病原体的天生的免疫是至关重要的.
- NLRC4炎症酶通过NLR家族的亡抑制蛋白 (NAIP) 感知细菌鞭毛蛋白或III型分泌系统 (T3SS) 的组成部分.
- 对于NLRC4炎症酶激活的调节尚不完全了解.
研究的目的:
- 研究干扰素调节因子8 (IRF8) 在NLRC4炎症酶激活中的作用.
- 确定IRF8是否影响其他炎症性途径.
- 评估IRF8在宿主防御细菌感染中的意义.
主要方法:
- 使用来自骨髓的巨细胞感染了Salmonella Typhimurium,Burkholderia thailandensis和Pseudomonas aeruginosa.
- 在IRF8存在或不存在的情况下评估NLRC4炎症酶激活.
- 评估了IRF8对NAIP转录的影响.
- 检查了IRF8在体内炎症依赖性细胞因子产生和热的作用.
主要成果:
- 针对萨尔蒙氏菌,泰国菌和伪菌的最佳NLRC4炎症酶激活需要IRF8.
- 对于正规和非正规的NLRP3,AIM2和Pyrin炎症酶激活,IRF8是不可用的.
- IRF8控制NAIP转录,使得对NLRC4激活进行鞭毛蛋白或T3SS组件检测.
- 在体内,IRF8通过炎症酶介导的细胞因子释放和灭,对细菌感染提供保护.
结论:
- IRF8是NAIP和NLRC4炎症酶激活的关键调节剂.
- IRF8在对抗细菌感染的宿主防御中起着关键作用.
- IRF8通过依赖炎症酶的机制增强免疫力.
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