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. Overall design: 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）作为莱姆病的螺旋体病原体，拥有庞大的脂蛋白家族，其在介导病原体与蜱虫及脊椎动物宿主细胞的特异性相互作用中发挥关键作用。尽管目前已有大量研究阐明了疏螺旋体脂蛋白对免疫调节通路的调控效应，但借助多组学方法解析脂蛋白诱导小鼠骨髓源性巨噬细胞（bone-marrow macrophages, BMDM）的宿主细胞应答相关转录组与蛋白质组模式，助力鉴定出更多效应因子及调控通路。单细胞RNA测序结果显示，BMDM内存在空间异质性。基因表达分析表明，MAPK、TLR、NOD、趋化因子、T细胞受体信号通路相关基因在BMDM中被显著激活，无偏倚蛋白质组学分析验证了上述发现。总体实验设计：本研究采用单细胞RNA测序技术，分析暴露于纯化疏螺旋体脂蛋白的C3H/HeN小鼠骨髓源性巨噬细胞的转录组变化，以期揭示参与莱姆病炎症应答的分子特征。