巨细胞促进结核病的病理和易感性
Ananya Gupta1,2, Vibha Taneja1, Javier Rangel Moreno3
1The University of Chicago, Department of Microbiology, 920 East 58 Street, CLSC 1117, Chicago, IL 60637.
bioRxiv : the preprint server for biology
|September 24, 2024
概括
乳腺细胞通过产生基酶和改变活性肺结核 (PTB) 中的基因表达来促进结核病 (TB) 病理. 减少巨细胞可以改善感染控制,并减少小鼠模型中的肺炎.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 病理学 病理学 病理学
背景情况:
- 结核病 (TB) 影响全球四分之一的人口,潜在的结核感染 (LTBI) 可能会发展为活性肺结核 (PTB).
- 巨细胞 (MCs) 在活跃的PTB期间在肺部积累,并对Mycobacterium结核病 (Mtb) 暴露作出反应.
- 之前的研究指出,与LTBI相比,PTB增加了MCs.
研究的目的:
- 为了研究巨细胞在肺结核病发症中的作用.
- 在潜伏性结核病与活跃性结核病中表征瘤细胞基因表达特征.
- 评估针对结核病治疗的瘤细胞的治疗潜力.
主要方法:
- 对人类和的粒瘤中细胞基马酶的产生进行分析.
- 单细胞RNA测序 (scRNA seq) 用于比较LTBI和PTB中的MC基因表达.
- 评估MTB感染控制在乳腺癌缺少的小鼠.
主要成果:
- 在PTB颗粒瘤中的巨细胞主要产生基马酶.
- 在LTBI中的MCs显示TNF-alpha,胆固醇和TGF-beta信号通路的丰富.
- 在PTB中,MCs表现出IFN-,氧化酸化和MYC信号的特征.
- 在小鼠中,MC缺乏导致了Mtb控制的改善,减少了肺髓状细胞的积累,并减少了慢性炎症.
结论:
- 乳腺细胞在Mycobacterium结核病感染中起着病理作用.
- 杆细胞衍生基马酶和改变的信号通路有助于结核病的发病.
- 乳腺细胞代表了治疗结核病的潜在宿主导治疗点.
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