在生物膜感染期间,由粒细胞髓衍生的抑制细胞活动是由糖解/HIF1a轴调节的
Christopher M Horn1, Prabhakar Arumugam1, Zachary Van Roy1
1Department of Pathology, Microbiology, and Immunology and.
The Journal of clinical investigation
|February 29, 2024
概括
黄金葡萄球菌假肢关节感染 (PJI) 涉及到促进炎症的骨髓性衍生抑制细胞 (MDSC). 针对他们的新陈代谢,特别是糖解和缺氧反应,在PJI小鼠模型中减少了细菌负担.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 代谢工程是代谢工程.
背景情况:
- 黄金葡萄球菌是造成假肢关节感染 (PJI) 的主要原因,经常变得慢性.
- 颗粒细胞髓衍生抑制细胞 (G-MDSCs) 是慢性PJI的关键参与者,培养一种支持生物膜持久性的抗炎环境.
研究的目的:
- 调查G-MDSC中的代谢途径,这些代谢途径有助于PJI金黄色葡萄球菌的慢性性.
- 探索针对G-MDSC新陈代谢治疗S. aureus PJI的潜力.
主要方法:
- 单细胞RNA测序 (scRNA-Seq) 和生物信息代谢算法用于分析S. aureus PJI小鼠模型中的G-MDSC代谢.
- 药理上抑制糖解 (使用2-脱氧葡萄糖) 和基因向低氧诱导因子1-α (HIF1a) 途径在粒细胞中被使用 in vivo.
- scRNA-Seq也在人类PJI患者的粒细胞上进行.
主要成果:
- 在S. aureus PJI中的G-MDSC表现出显著丰富的糖解和缺氧反应通路.
- 在PJI小鼠模型中,干扰糖解和HIF1a在体内减弱了G-MDSC免疫抑制和减少了细菌负载.
- 对人类PJI患者粒细胞的分析证实了糖解和缺氧反应基因的丰富.
结论:
- 糖解/HIF1a轴对于G-MDSC介导的免疫抑制和S. aureus PJI中的生物膜持久性至关重要.
- 准这种代谢轴是一个潜在的治疗策略,用于管理慢性金黄色假肢关节感染.
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