由工程Listeria诱导的MAIT细胞表现出抗菌和抗瘤活性
bioRxiv : the preprint server for biology
|November 24, 2025
概括
产生利博弗拉的工程Listeria单细胞原体逃避粘膜关联不变T (MAIT) 细胞. 这种工程细菌,L. monocytogenes-ribDEAHT,可以被利用来激活MAIT细胞,用于潜在的抗感染和抗癌疗法.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 病原体逃生 病原体逃生
背景情况:
- 粘膜关联不变T细胞 (MAIT) 是丰富的与生俱来的类似T细胞,能够识别微生物代谢物.
- 一种通过食物传播的病原体Listeria monocytogenes缺乏 рибофлавин生物合成途径,可能会逃避MAIT细胞检测.
- 这种缺陷可能代表了L. monocytogenes的病变适应策略,以逃避宿主免疫反应.
研究的目的:
- 调查L. monocytogenes缺乏 рибофлавин生产是否是一种逃避MAIT细胞的机制.
- 探索工程L. monocytogenes菌株的治疗潜力,这些菌株可以激活MAIT细胞.
主要方法:
- 工程 L. monocytogenes 菌株 (L. monocytogenes-ribDEAHT) 用于生产 рибофлавин.
- 评估野生型和MAIT细胞缺陷小鼠中的细菌毒性.
- 评估MAIT细胞扩张和效应器功能 () 作为对感染的反应.
- 在传染病和癌症模型中测试L. monocytogenes-ribDEAHT的治疗疗效.
主要成果:
- 在野生型小鼠中,L. monocytogenes-ribDEAHT的毒性降低,但在缺乏MAIT细胞的小鼠中仍然具有毒性.
- 感染L. monocytogenes-ribDEAHT诱导了显著的MAIT细胞扩张,并且需要穿孔素来清除病原体.
- L. monocytogenes-ribDEAHT 提供了对弗朗西塞拉 (Francisella tularensis) 肺部感染的保护.
- 这种工程细菌抑制了瘤的生长,即使没有CD8+ T细胞.
结论:
- 对于逃避MAIT细胞监测而言,L. monocytogenes在利博弗拉合成中的缺陷至关重要.
- 改造的L. monocytogenes菌株可以有效地激活MAIT细胞.
- 激活的MAIT细胞对抗传染病和癌症具有治疗前景.
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