肠道低丰富的细菌驱动MyD88/Trif-依赖的CD8+T细胞在慢性髓性白血病中耗尽
Francesca Ronchi1, Magdalena Hinterbrandner2, Viviana Rubino2
1Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Bern, Switzerland; Charité - Universitaetsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany; Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Berlin, Germany.
某些肠道细菌,特别是Sutterella物种,可以阻碍免疫系统.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 在瘤学瘤学.
背景情况:
- 白血病干细胞 (LSCs) 对传统疗法和免疫监测具有抗性.
- 通过LSCs逃避细胞毒性T细胞 (CTL) 中介消除的机制仍然不完全理解.
研究的目的:
- 研究肠道共生素在调节抗白血病免疫力对慢性髓性白血病 (CML) 的作用.
- 确定影响CML中LSC存活率和CTL功能的特定细菌物种.
主要方法:
- 使用了没有细菌和没有特定机会性病原体的CML小鼠模型.
- 殖民小鼠具有特定的细菌菌株,包括Sutterella物种.
- 评估了CTL耗尽标志物,细胞因子生产 (干扰素-γ,巨酶B),体外LSC杀死,以及转录组形状.
主要成果:
- 没有细菌的小鼠表现出对CML进展的保护.
- 用Sutterella菌株的殖民,但不是其他细菌,重建了CML的进展.
- 较高的Sutterella患病率与MyD88/Trif-依赖的CTL疲劳相关,其特征是抗白血病免疫力受损.
结论:
- 特定的肠道共生物,特别是苏特雷拉物种,在CML中积极抑制抗白血病免疫力.
- 苏特雷拉物种被确定为CTL功能障碍的关键调节者,有助于CML进展.
- 这项研究揭示了肠道微生物群组成和LSCs的免疫调节之间的直接联系,这表明了新的治疗点.
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