Work

B. burgdorferi infection alters synovial macrophage response in a human ex vivo model of Lyme Arthritis 3674

Year: 2025

Type: article

Abstract: Description B. burgdorferi (Bb) is the causative agent of Lyme Disease and Lyme Arthritis (LA). After initial dissemination from skin to the blood and beyond, Bb may continue to persist in protected spaces such as the joints. The objective of this work was to evaluate how Bb alters joint lining macrophage function to perpetuate infection and inflammation in. To do this, we recruited 17 patients receiving open joint surgery and acquired synovium that otherwise would have been discarded. Patients could not have known rheumatologic disease or be on immunomodulatory medications. We infected the tissue in our transwell system that replicates the joint space on the bench. We used histomorphometry, immunofluorescence (IF), ELISA, and RNAscope to evaluate the functional alterations of the tissue over 3 days with 3 Bb doses. We found Bb infection thinned the joint lining macrophage layer at low (250k) and medium (500k) dose infection, but thickened this layer at high (1000k) infection at 24 hours. The tissue recovered by 48 hours. This coincided with loss of intimal border integrity (% intact border) at 24-48 hours, which recovered by 72 hours. RNAscope demonstrated the Bb was able to penetrate tissue by 24 hours, which decreased CD206 and iNOS signal by IF. ELISA demonstrated a decreased OPG:sRANKL ratio at 48 and 72 hours, indicating increased risk of bone/cartilage damage. Therefore, Bb quantifiably alters both structure and function of human tissue in our novel, human, ex vivo explant system. Funding Sources Supported by Start-up Funding provided by the Department of Emergency Medicine. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1445