TLR初始化许可证NAIP由免疫扩散性连接体激活炎症酶
James P Grayczyk1, Luying Liu1, Marisa S Egan2
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104.
概括
收费类受体 (TLR) 信号增强了小鼠巨细胞中的NLRC4表达,使NAIP/NLRC4炎症体能够检测出通常逃避检测的细菌成分. 人类巨细胞缺乏这种TLR诱导的增强,突出了特定物种的免疫反应.
科学领域:
- 这是天生的免疫力.
- 炎症有一些生物学.
- 微生物传感器是一种微生物传感器.
背景情况:
- 作为NLR家族,亡抑制蛋白 (NAIPs) 和NLRC4形成炎症体,以检测细菌鞭毛蛋白和III型分泌系统 (T3SS).
- 一些细菌成分通过不结合NAIPs来逃避NAIP/NLRC4炎症体传感.
- NLRC4是构成性表达的,通常不是由炎症信号诱导的.
研究的目的:
- 通过炎症信号来研究NLRC4表达的调节.
- 了解NLRC4表达水平如何影响NAIP/NLRC4炎症酶对逃避性细菌配体的激活.
- 探索NLRC4.4的TLR介导调节中的特定物种差异.
主要方法:
- 用托尔类受体 (TLR) 激动剂治疗小鼠和人类巨细胞.
- 分析NLRC4转录和蛋白质表达,使用定量PCR和西式涂抹.
- 测量了对细菌连接体的反应的热诱导.
- 在巨细胞中进行了NLRC4的宫外表达.
主要成果:
- 在TLR-依赖的p38 MAPK信号上调的NLRC4转录和蛋白质表达在小鼠巨细胞.
- 这种上升调节使得小鼠巨细胞能够检测到以前逃避的细菌连接体.
- 在人体巨细胞中,TLR初始化并没有提高NLRC4的调节,这些巨细胞仍然无法检测逃避性联结体.
- 异位NLRC4表达在小鼠和人类细胞中都恢复了通过逃避性连接体诱导热的作用.
结论:
- TLR原始化调节了小鼠NAIP/NLRC4炎症酶的激活值.
- 增加的NLRC4水平对于检测免疫扩散性或低于最佳的NAIP配体至关重要.
- 对NLRC4的物种特异性TLR调节会影响对细菌病原体的炎症体反应.
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