Ly6G+来自粒细胞的IL-17限制了保护性宿主反应,并促进了结核病的发生
Priya Sharma1, Raman Deep Sharma1, Binayak Sarkar2
1Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
eLife
|February 5, 2026
概括
准IL-17-COX2-Ly6G+颗粒细胞轴可以预防结核病. 这个轴促进了Mycobacterium结核病 (Mtb) 感染,IL-17和COX2对保护和患者的结果产生了负面影响.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 结核病研究 结核病研究
背景情况:
- 对 Mycobacterium tuberculosis (Mtb) 的免疫反应是复杂的,保护性相关性尚未完全理解.
- 在Mtb感染期间,Ly6G+粒细胞 (Ly6G+Gra),IL-17和COX2都与宿主-病原体相互作用有关.
研究的目的:
- 阐明IL-17-COX2-Ly6G+Gra轴在Mtb病变发生过程中的作用.
- 研究这一轴作为结核病 (TB) 的潜在治疗点.
主要方法:
- 研究是在Mtb感染的野生型和Ifng-/-小鼠中进行的.
- 干预措施包括抗IL-17单克隆抗体 (mAb) 中和,赛莱可西布 (COX2抑制剂) 和RORγt抑制.
- 分析包括评估Ly6G+Gra透,细菌负担,病理和IL-17水平.
- 分析了与中性粒细胞计数和IL-17与治疗结果相关联的人类患者数据.
主要成果:
- 在受感染的小鼠中,Ly6G+Gra移植了细胞内Mtb.
- 在Ifng-/-小鼠中,过度的Ly6G+Gra透与严重疾病相关;IL-17中和COX2抑制改善了结果.
- Ly6G+Gra是MTB感染肺部IL-17的主要来源.
- 抑制IL-17,COX2或RORγt减少了Ly6G+Gra中的细菌负担,并改善了WT小鼠的肺病理.
- 通过向Ly6G+Gra居住的Mtb,COX2抑制提高了BCG疫苗的疗效.
- 在肺结核患者中,高中性粒细胞计数和IL-17水平与不良治疗结果相关.
结论:
- IL-17-COX2-Ly6G+Gra轴代表了Mtb感染中的亲病原性途径.
- IL-17和COX2作为负相关的保护作用.
- 针对这一轴为结核病预防和治疗提供了一个有前途的战略.
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