Extracellular Vesicles Derived from Borrelia burgdorferi Leads to Prolonged Neuroinflammation in Lyme Disease

It is estimated that 10-20% of patients treated using antibiotics for Lyme disease develop post-treatment Lyme disease syndrome (PTLDS), characterized by decline in cognitive testing, processing speed, verbal recall, and working memory. The cause and pathology of PTLDS is still an area of active research. Production of reactive oxygen species (ROS) along with mitochondrial interaction with immune proteins such as toll-like receptors (TLRs) and interferons are critical in regulating inflammation. There is currently little research regarding mitochondrial ties to inflammation in Lyme disease. Bacterial extracellular vesicles (BEVs) from cultured Borrelia burgdorferi B31 were found to contain immunogenic molecules. HMC3 human microglial cells were treated with Borrelia BEVs overnight. Total RNA was then collected and PCR was used to amplify expressed genes. The HMC3 cells showed upregulated expression of interferon-alpha (IFN-α), aconitate decarboxylase 1 (Acod1), and toll-like receptor 2, 4, and 9 (TLR2, TLR4, TLR9). These findings suggest mitochondrial metabolic functions along with pathways such as ROS production or energy metabolism modulated by Acod1 may be disrupted, activating proinflammatory genes and contributing to persistent neuroinflammation. Thus, mitochondrial dysfunction from exposure to Borrelia BEVs can promote a proinflammatory state. This supports Borrelia BEVs as antigenic reservoirs driving chronic symptoms, with potential as diagnostic markers and therapeutic targets.