中性粒细胞和加勒-3保护小鼠免受致命的细菌感染,人类免受急性呼吸衰竭
Sudipta Das1, Tomasz W Kaminski2, Brent T Schlegel3
1Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine and Acute Lung Injury Center of Excellence, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
Nature communications
|June 3, 2024
概括
之前暴露于脂聚糖 (LPS) 训练了天生的免疫系统,增强了对致命的Pseudomonas aeruginosa感染的中性粒细胞和巨细胞防御. 这种LPS介导的保护涉及galectin-3,一种关键的抗菌蛋白,提供了一种新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 传染性疾病 传染性疾病
背景情况:
- 伪菌的呼吸道感染构成危及生命的风险,特别是在因抗生素耐药性而入院的患者中.
- 免疫系统教育对抗P. aeruginosa的潜力仍然是一个重要的研究问题.
研究的目的:
- 调查先前暴露于脂多糖 (LPS) 能否防止致命的P. aeruginosa感染.
- 阐明潜在的先天性免疫机制,重点关注中性粒细胞,巨细胞和甲-3.
主要方法:
- 在致命的P. aeruginosa挑战之前,小鼠接受了低剂量的LPS.
- 分析了免疫细胞种群,基因表达 (细胞灭菌,细胞杀死) 和加勒-3水平.
- 他们使用了肠道成像,杀死细菌的测试,以及缺乏加勒-3的小鼠.
- 从急性呼吸衰竭病例中获得的人类患者数据 (内气管吸入物) 分析了加勒-3和免疫细胞特征.
主要成果:
- 在小鼠中,LPS的预暴露给予了对致命的P. aeruginosa感染的保护.
- LPS训练了天生的免疫系统,扩大了中性粒细胞和间歇性巨细胞群体,增强了细胞和杀细胞基因表达.
- 中性粒细胞独特表达Lgals3 (编码加勒-3),这是LPS介导保护的关键组成部分.
- 腹腔内吸收物中高高的加列-3水平与急性呼吸衰竭患者的存活率和有利的低炎症亚表型相关.
结论:
- 之前的LPS暴露有效地训练了天生的免疫力,为致命的P. aeruginosa感染提供了保护.
- 中性粒细胞和抗菌蛋白 galectin-3 是这种LPS诱导的保护机制的核心.
- 呼吸道分泌中的加勒-3水平可能作为急性呼吸衰竭患者的预后生物标志物.
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