结核菌依赖的单细胞表达量特征位置和结核病原体
Hyejeong Hong1, Kimberly A Dill-McFarland2, Jason D Simmons2
1Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, USA.
medRxiv : the preprint server for health sciences
|September 11, 2023
概括
人类髓状细胞对Mycobacterium tuberculosis (Mtb) 具有遗传编码的反应. 单细胞中的这些依赖Mtb的eQTLs会影响细胞因子的表达和对结核病感染的抵抗力.
科学领域:
- 免疫遗传学 免疫遗传学
- 基因组学就是基因组学.
- 传染性疾病 传染性疾病
背景情况:
- 结核病 (TB) 中的宿主-病原体相互作用是复杂的,在暴露于Mycobacterium tuberculosis (Mtb) 后的结果各不相同.
- 人类髓状细胞可能对mtb具有遗传决定的反应,这会影响结核病的发病.
研究的目的:
- 为了确定与结核病发病相关的Mtb特定的,单细胞驱动的表达定量特征位点 (eQTLs).
- 研究这些eQTLs,细胞因子表达和对Mtb感染标志物的临床耐药性之间的联系.
主要方法:
- 使用RNA测序对乌干达结核病例家庭接触者的单细胞进行全基因组eQTL映射.
- 对依赖mtb的eQTLs及其与细胞因子水平及其结核素皮肤试验 (TST) /干扰素-γ释放试验 (IGRA) 转换的分析.
- 网络和路径丰富分析.
主要成果:
- 在Mtb感染单细胞中鉴定了1567个cis-eQTL,在16个基因中有29个Mtb依赖的eQTL.
- 与Mtb诱导的细胞因子表达相关的eQTLs子集 (n=8) 和对TST/IGRA转换的临床耐药性 (n=1).
- BMP6,一个依赖Mtb的eQTL,与IFNB1诱导有关;脂肪酸代谢成为一个相关的途径.
结论:
- 单细胞基因含有依赖Mtb的eQTL,影响免疫反应.
- 这些发现提供了对免疫遗传途径的见解,这些途径控制了对Mtb感染和结核病发展的易感性.
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