外围原始化诱导了用于病原体制所需的循环中性粒细胞中的塑性转录组和蛋白组反应
Rainer Kaiser1,2, Christoph Gold1,2, Markus Joppich3
1Department of Medicine I, LMU University Hospital, LMU Munich, Germany.
Science advances
|March 22, 2024
概括
循环中性粒细胞通过上调抗微生物基因来适应感染,增强病原体的制. 这种转录可塑性对于在急性细菌感染期间重编程中性粒细胞功能至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 传染性疾病 传染性疾病
背景情况:
- 中性粒细胞是响应感染的关键免疫细胞,但它们在循环中的功能适应性尚不清楚.
- 之前的研究受限于在疾病期间研究人类中性粒细胞的实验挑战.
研究的目的:
- 调查在细菌感染期间循环中的人类和小鼠中性粒细胞的转录和蛋白质变化.
- 阐明转录性可塑性在中性粒细胞功能重编程中的作用.
主要方法:
- 采用创新的固定技术和基于单细胞的转录和蛋白质分析.
- 在稳定状态和细菌感染期间,分析了人类和小鼠模型中的中性粒细胞反应.
- 研究了阻断de novoRNA合成对中性粒细胞适应的影响.
主要成果:
- 在循环中的中性粒细胞中发现了抗微生物基因的保守上调,增强了病原体的制.
- 在炎症期间证明了中性粒细胞激活标志物 (例如CD177/NB-1) 的TLR4/NF-κB信号依赖上调.
- 表明抑制RNA合成可以防止中性粒细胞的适应和在感染时对效应分子的上调调节.
结论:
- 转录性可塑性是急性感染期间循环中的功能性中性粒细胞重编程的关键机制.
- 这种重新编程通过对特定的效应分子进行上调来促进细菌的制.
- 研究结果提供了对中性粒细胞行为和传染病潜在治疗点的见解.
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