Unique features of B. burgdorferi peptidoglycan drive persistence in discrete tissues and cause responses that mimic chronic illness 2257865

Abstract

Abstract Introduction Each year there are roughly 500,000 new Lyme disease cases in the United States. Lyme disease, caused by Borrelia burgdorferi, presents with nonspecific flu-like symptoms, and can progress into more severe symptomology. Lyme arthritis is the most common late-stage symptom of Lyme disease affecting ∼10% of patients. Recent studies identified a specific bacterial component that persists within the synovial fluid of post treatment Lyme arthritis patients — B. burgdorferi peptidoglycan (BbPG). PG is a pathogen associated molecular pattern recognized by specific innate immune receptors and causes a proinflammatory response. Small changes in PG chemistry impact immune recognition. BbPG is unique compared to canonical PG chemistry, is released into the environment during normal bacterial growth, and is arthritogenic when injected into a murine model. Methods To investigate the relationship between BbPG and Lyme arthritis we developed a novel in vivo imaging system to track the biodistribution of fluorescent BbPG in real time in a murine model. This approach was coupled with multiomic studies to determine the impact of BbPG on specific tissues and cell types. Results These studies identified that BbPG persists within the murine liver for weeks compared to typical PG structures, is preferentially engulfed and retained by hepatocytes and Kupffer cells, and impacts pathways involving energy metabolism. Conclusion These findings highlight how the persistence of a unique pathogen associated molecular pattern can result in prolonged immune responses and chronic symptomology. Funding Source Steven and Alexandra Cohen Foundation, Global Lyme Alliance, Bay Area Lyme Foundation, NIAID Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)