细胞死亡途径的可塑性确保了Yersinia伪结核病感染期间的GSDMD激活
Felicia Hui Min Chan1, Hui Wen Yeap1, Zonghan Liu1
1Immunology Translational Research Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
Cell reports
|January 17, 2025
概括
耶尔西尼亚伪结核病感染会在缺乏YopJ或caspase-8的巨细胞中触发炎性酶激活. 卡斯巴酶-11对于控制体内细菌负担至关重要,突出显示免疫路径的可塑性.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 巨细胞利用模式识别和细胞因子受体对抗微生物感染的先天免疫反应.
- 像Yersinia伪结核病这样的病原体已经进化了机制,例如YopJ效应蛋白,以抑制宿主免疫信号通路.
- YopJ抑制了TAK1信号传递,促进了RIPK1依赖的复合组合和气皮素D (GSDMD) 的卡斯帕-8激活,从而导致热亡.
研究的目的:
- 在没有YopJ或caspase-8的情况下,研究巨细胞对Yersinia感染的反应.
- 阐明 caspase-11 在控制 Yersinia 感染期间的细菌负担中的作用.
- 了解细胞死亡途径的可塑性,以确保GSDMD的激活.
主要方法:
- 在巨细胞中利用了Yersinia伪结核病感染模型.
- 评估了炎症酶激活,特别是非正规的炎症酶通路.
- 研究了YopJ,caspase-8和caspase-11在巨细胞反应和细菌清除中的作用.
主要成果:
- 失去YopJ或其催化活性会诱导巨细胞中非正规的炎症酶激活.
- 卡斯帕斯-11对于限制Yersinia细菌负担在体内至关重要.
- Yersinia 伪结核病侵入巨细胞质中,当 caspase-8 活性较低时,会触发非正规的炎症酶激活.
结论:
- 巨对Yersinia感染的反应表现出可塑性,通过替代途径确保GSDMD的激活.
- 非规范性炎症酶激活,依赖于caspase-11,是对Yersinia的关键宿主防御机制.
- 了解这些途径可以了解宿主-病原体相互作用和潜在的治疗点.
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