炎症性ER应激反应决定了全身 кандидоз的免疫病原性进展
Deepika Awasthi1, Sahil Chopra1,2, Byuri A Cho3
1Department of Obstetrics and Gynecology, and.
The Journal of clinical investigation
|July 11, 2023
概括
系统性Candida albicans感染导致致命的脏炎症,原因是肌肉细胞中需要因诺醇的酶1α (IRE1α) 过度激活. 抑制白细胞中的IRE1α信号减少了炎症,并改善了小鼠的存活率.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 病原体的识别 病原体的识别
背景情况:
- 需要内醇的酶1α (IRE1α) 是内细胞网膜 (ER) 应激反应的关键组成部分,在先天免疫系统中,对恒常性和对细菌和病毒感染的免疫反应至关重要.
- IRE1α信号在对真菌病原体,特别是Candida albicans的先天性免疫反应中的特定作用尚未确定.
研究的目的:
- 研究IRE1α信号传递在对系统性Candida albicans感染的先天免疫反应中的作用.
- 阐明IRE1α信号传导在候群病期间对脏免疫病理有所贡献的机制.
- 评估针对散播性角膜病的IRE1α的治疗潜力.
主要方法:
- 在使用Candida albicans的小鼠中诱导系统性感染.
- 分析IRE1α激活和髓状细胞下游炎症媒介表达.
- 评估反应性氧物种 (ROS) 生产和ER压力.
- 在白细胞中选择性地切除IRE1α和IRE1α的药理抑制.
- 评估脏免疫病理学和动物生存率.
主要成果:
- 系统性Candida albicans感染导致神经骨髓细胞中的IRE1α过活化,导致严重的免疫病理和死亡.
- IRE1α激活是由同时发生的Toll-like受体/IL-1R适应蛋白MyD88和dectin-1信号驱动的,导致ROS的产生,ER压力和炎症调解物的过度表达 (IL-1β,IL-6,CCL5,PGE2,TNF-α).
- 在白细胞中,IRE1α的遗传删除或药理抑制显著降低了脏炎症,并延长了感染小鼠的存活时间.
结论:
- 天生的IRE1α信号在系统性Candida albicans感染的免疫病原发生中发挥着关键作用.
- IRE1α过度激活通过促进关键炎症介质的过度表达,导致致命的炎.
- 向IRE1α代表了一种潜在的治疗策略,以减轻蔓延性 кандидоз的有害影响.
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