双重中性粒细胞子集通过IL-1β或PD-L1加剧或抑制结核病的炎症
Emilie Doz-Deblauwe1, Badreddine Bounab1, Florence Carreras1
1INRAE, Université de Tours, Nouzilly, France.
Life science alliance
|May 28, 2024
概括
结核病 (TB) 中的两个中性粒细胞子集起到相反的作用. 炎性中性粒细胞恶化疾病,而调节性中性粒细胞通过抑制T细胞反应来保护,这种功能被某些结核病菌株破坏.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 中性粒细胞是关键的免疫细胞,在结核病 (TB) 发病过程中具有双重作用.
- 了解中性粒细胞异质性对于破译结核病免疫反应至关重要.
研究的目的:
- 为了研究菌根菌感染的肺部中性粒细胞的不同子集.
- 阐明结核病中这些中性粒细胞子集的功能作用和调节机制.
主要方法:
- 基于感染小鼠肺部MHC-II和PD-L1表达的显著中性粒细胞子集.
- 分析了炎症酶的活性,细胞因子的产生 (IL-1β,IFN-γ) 和T细胞的增殖.
- 使用了淘汰赛小鼠模型 (IFN-γR-/-) 和特定的真菌菌株 (HN878).
主要成果:
- 确定了炎症性 (MHC-II,PD-L1lo) 和调控性 (MHC-II+,PD-L1hi) 中性粒细胞子集.
- 炎症性中性粒细胞产生IL-1β,加剧肺炎,特别是在IFN-γR-/-小鼠.
- 调控性中性粒细胞通过PD-L1抑制T细胞增殖和IFN-γ的产生,这取决于IFN-γR的信号传递.
- 超病毒性HN878菌株损害了调节性中性粒细胞功能,导致过度炎症.
结论:
- 中性粒细胞子集在结核病期间差异调节炎症.
- 通过调节性中性粒细胞抑制PD-L1介导的抑制是关键的宿主防御机制.
- 病毒性菌根菌对这一调节轴的干扰会导致严重的肺炎,并可能在接受抗PD-L1治疗的癌症患者中告知TB的重新激活.
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