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

Kari An Mulford; Rachel Johnson; Katherine L. Butler; Jessica Dennis; Jacob M. Elkins; Christy Petersen; Karen I. Cyndari

doi:10.1093/jimmun/vkaf283.1445

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

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

Kari An Mulford, Rachel Johnson, Katherine L. Butler, Jessica Dennis, Jacob M. Elkins, Christy Petersen and Karen I. Cyndari

The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2831445

11/01/2025

DOI: 10.1093/jimmun/vkaf283.1445

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Abstract

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)

Animals - Human Cells - Monocytes/Macrophages Infections - Bacterial Molecules - Nitric Oxide Processes - Inflammation

Details

Title: Subtitle: B. burgdorferi infection alters synovial macrophage response in a human ex vivo model of Lyme Arthritis 3674
Creators: Kari An Mulford - University of Iowa
Rachel Johnson - University of Iowa
Katherine L. Butler - University of Iowa
Jessica Dennis - University of Iowa
Jacob M. Elkins - University of Iowa
Christy Petersen - The Ohio State University
Karen I. Cyndari - University of Iowa
Resource Type: Abstract
Publication Details: The Journal of immunology (1950), Vol.214(Supplement_1), vkaf2831445
DOI: 10.1093/jimmun/vkaf283.1445
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: Oxford University Press
Grant note: Department of Emergency Medicine
Supported by Start-up Funding provided by the Department of Emergency Medicine.
Alternative title: IMMUNOLOGY2025™ Abstracts
Language: English
Date published: 11/01/2025
Academic Unit: Epidemiology; Emergency Medicine; Orthopedics and Rehabilitation; Internal Medicine
Record Identifier: 9985035033302771

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