# Borrelia burgdorferi mitogen in development of arthritis

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $457,500

## Abstract

Project Summary/Abstract
Lyme disease, caused by the tick transmitted pathogen Borrelia burgdorferi, is estimated to be responsible for
300,000 new cases per year in the United States. Disease manifestations include a skin lesion at the site of
the tick bite, followed by disseminated symptoms including secondary skin lesions, arthritis, Bell’s palsy,
peripheral neuropathies, meningitis/encephalitis, and carditis. Most individuals respond to antibiotic treatment,
particularly if started early in infection, however, up to 20% of patients experience a delay in the return to
normal health. This persistence of symptoms following antibiotic treatment is termed post treatment Lyme
disease symptoms, PTLDS, and encompasses disseminated symptoms including neurological abnormalities,
fatigue, and arthritis. The underlying mechanism of sustained symptoms is not understood and is an area of
active investigation. Hypotheses include presence of persister spirochetes, presence of pro-inflammatory
bacterial fragments, dysregulation of anti-inflammatory processes, and emergence of auto-reactive B and T
lymphocytes. The lack of easily manipulated animal model has limited understanding of chronic disease.
Using the IL-10 deficient mouse as a model for joint disease that persists following immune-mediated
clearance of B. burgdorferi, we have identified bystander activation of T lymphocytes that drive IFN
dependent arthritis. Bystander activation of T cells is independent of classic MHC-TCR engagement, but
dependent on T cell intrinsic expression of TLR2. We have also found that patients with PTLDS have elevated
numbers of activated CD4+ and CD8+ T cells in their peripheral blood, when compared with patients who return
to normal health. We will expand molecular characterization of bystander-activated T cells in mice and
patients in order to identify novel targets for therapeutic intervention. These will be tested in the IL-10-/- model
of chronic Lyme disease. Preliminary studies indicate short-term targeting of TLR2 is potential therapeutic for
Lyme arthritis. The overall goal of study is to identify novel treatments for chronic Lyme disease that target
inappropriately activated T cells without compromising host defense.

## Key facts

- **NIH application ID:** 10215528
- **Project number:** 5R01AI032223-25
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Janis J. Weis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $457,500
- **Award type:** 5
- **Project period:** 1993-04-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215528

## Citation

> US National Institutes of Health, RePORTER application 10215528, Borrelia burgdorferi mitogen in development of arthritis (5R01AI032223-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10215528. Licensed CC0.

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