尽管在莱什曼病感染的中接受了米尔特福辛治疗,但仍然存在持续的髓状细胞重编程
Morgane Picard1, Steven Boutrais2, Vasco Rodrigues1
1INSERM-U1124, Université Paris Cité, Paris, France.
iScience
|December 1, 2025
概括
在中治疗内脏莱什曼病 (VL) 的米尔特福辛治疗并没有完全清除寄生虫. 在治疗后,脏中的髓状细胞重编程表明了慢性感染和寄生虫持久性的机制.
科学领域:
- 免疫学 免疫学 免疫学
- 寄生虫学的寄生虫学
- 热带疾病 热带疾病
背景情况:
- 内脏莱什曼病 (VL) 是一种被忽视的热带疾病,由原生虫寄生虫引起,引发炎症反应和组织损伤.
- 早期感染会导致炎症,因此及时治疗至关重要.
研究的目的:
- 在 rhesus macaque 模型中,评估在内脏莱什曼病急性阶段的米尔特福森治疗对 rhesus macaque 模型的影响.
- 为了研究寄生虫的持久性和治疗后宿主免疫反应.
主要方法:
- 患有VL的 rhesus macaques 在急性感染阶段被用米尔特福辛治疗.
- 单细胞转录组分析和流细胞测量被用于分析骨髓状细胞和治疗后的寄生虫存在.
主要成果:
- 寄生虫在多种组织 (脏,骨髓,淋巴结) 中持续存在,尽管接受了米尔特福辛治疗.
- 寄生虫负担与细胞中的米尔特福辛水平相反相关.
- 单细胞分析揭示了骨髓状细胞的重编程,包括炎性巨细胞和树突细胞 (DCs),治疗后三个月可以检测到L.infantum.
结论:
- 在急性VL期间的米尔特福辛治疗不能保证寄生虫清除,在关键组织中观察到持久性.
- 治疗后骨髓细胞的重编程表明,先天的免疫格局受到干扰.
- 骨髓细胞重编程可能导致慢性感染和持续的寄生虫在内脏莱什曼病的持久性.
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