Single-cell RNA seq identifies genes regulating the inflammatory pathways activated by purified Borrelia burgdorferi lipoproteins in murine bone marrow derived macrophages

Borrelia burgdorferi, the spirochetal agent of Lyme disease, has a large constellation of lipoproteins that play a prominent role in mediating pathogen-specific interactions with tick and vertebrate host cells. Although there is a large body of information on the effects of borrelial lipoproteins on immune modulatory pathways, the application of multi-omics methodologies to decode the transcriptional and proteomic patterns associated with host cell responses induced by lipoproteins in murine bone-marrow macrophages (BMDM) have helped identify additional effectors/pathways. Single-cell RNA seq revealed spatial heterogeneity within BMDM. Gene expression analysis showed that genes involved in pathways such as MAPK, TLR, NOD, chemokines, T-cell receptor signaling are activated in BMDM with unbiased proteomics analysis corroborating these findings. We used single-cell RNA-Seq to study the transcriptional changes in murine bone marrow derived macrophages from C3H/HeN mice exposed to purified borrelial lipoproteins, to uncover the molecular signatures that contribute to inflammatory responses in Lyme disease.

伯氏疏螺旋体（Borrelia burgdorferi）是莱姆病的致病螺旋体，拥有一套庞大的脂蛋白家族，在介导病原体与蜱虫及脊椎动物宿主细胞的特异性互作中发挥核心作用。尽管目前已有大量关于疏螺旋体脂蛋白对免疫调控通路影响的研究成果，但借助多组学（multi-omics）方法解析伯氏疏螺旋体脂蛋白诱导小鼠骨髓来源巨噬细胞（BMDM）的宿主细胞应答相关的转录组与蛋白质组模式，帮助研究人员发现了更多效应分子与调控通路。单细胞RNA测序（Single-cell RNA-seq）结果显示，BMDM群体内部存在空间异质性。基因表达分析表明，BMDM中丝裂原活化蛋白激酶（MAPK）、Toll样受体（TLR）、核苷酸结合寡聚化结构域受体（NOD）、趋化因子及T细胞受体信号通路相关基因均被激活，无偏倚蛋白质组学分析验证了上述发现。本研究采用单细胞RNA测序技术，对暴露于纯化伯氏疏螺旋体脂蛋白的C3H/HeN小鼠骨髓来源巨噬细胞的转录组变化进行分析，旨在揭示参与莱姆病炎症应答的分子特征。