Spatial Transcriptomic Profiling Reveals Joint Inflammation Signatures in Borrelia burgdorferi–Infected C3H Mice

Although multiple studies have been performed on the complex host immune response in Lyme arthritis, the spatial gene expression environment in the joint tissue remains unexplored. Here, we applied spatial transcriptomics to ankle joints of C3H mice infected with B. burgdorferi, profiling tissues at peak inflammation (2 weeks post infection) and after antibiotics (4 weeks post-infection) during inflammation resolution.

Analysis revealed spatially restricted signatures: pro-inflammatory responses dominated synovial and fibroblast populations 2 weeks post-infection, with elevated levels of Vimentin and I-Ek related gene and protein expression localized to these regions. In contrast, 4 weeks post-infection during the inflammation resolution phase, levels of Vimentin and I-Ek related gene and protein expression are reduced drastically despite the persistent pathology seen by H&E staining.