结核菌依赖单细胞表达量的特征位点,细胞因子的产生,以及结核病原性
Hyejeong Hong1, Kimberly A Dill-McFarland2, Jason D Simmons2
1Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, United States.
Frontiers in immunology
|March 22, 2024
概括
人类髓状细胞对Mycobacterium tuberculosis (Mtb) 具有遗传编码的反应,这些反应会影响结核病 (TB) 易感性. 单细胞中的这些依赖Mtb的eQTL与细胞因子的表达和对感染的抵抗有关.
科学领域:
- 免疫遗传学 免疫遗传学
- 宿主-病原体相互作用
- 结核病的发病因子
背景情况:
- 在暴露于Mycobacterium tuberculosis (Mtb) 后结核病 (TB) 结果的异质性尚不清楚.
- 主体-病原体的共同进化表明,遗传编码的反应可能调节结核病的发生.
研究的目的:
- 为了确定Mtb特定的,单细胞依赖表达量的特征位点 (eQTLs).
- 调查这些eQTL与细胞因子表达和对结核病感染标志物的临床耐药性的关联.
主要方法:
- 在乌干达结核病例家庭接触者的Mtb感染单细胞中使用RNAseq进行全基因组eQTL映射.
- 分析依赖mtb的eQTL及其与细胞因子表达和结核素皮肤试验 (TST) /干扰素-γ释放试验 (IGRA) 转换的相关性.
主要成果:
- 在Mtb感染单细胞中鉴定了1567个cis-eQTL,其中29个是Mtb依赖的.
- 与Mtb诱导的细胞因子表达和/或对TST/IGRA转换的临床抵抗相关的eQTLs的一个子集.
- BMP6,一个依赖Mtb的eQTL,与IFNB1诱导相关;脂肪酸代谢被确定为相关途径.
结论:
- 单细胞基因含有依赖Mtb的eQTLs,这些基因会影响结核病的易感性.
- 这些发现提供了对调节Mtb感染和结核病发病的免疫遗传途径的见解.
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