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.