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bioRxiv · 10.1101/2024.11.24.625079

Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi-infected mice

Yu, Q.·Tang, X.·Hart, T.·Homer, R.·Belperron, A. A.·Bockenstedt, L.·Ring, A.·Nakamura, A.·Fikrig, E.
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Abstract

Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with B. burgdorferi, but only develop mild joint inflammation, was therefore examined. SLPI-deficient C57BL/6 mice challenged with B. burgdorferi had a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues of B. burgdorferi-infected SLPI-deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. B. burgdorferi-infected SLPI-deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (BActerial Selection to Elucidate Host-microbe Interactions in high Throughput) library, we found that SLPI directly interacts with B. burgdorferi. These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.

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Yu, Q., Tang, X., Hart, T., Homer, R., Belperron, A. A., Bockenstedt, L., Ring, A., Nakamura, A., Fikrig, E.. 2024-11-25. Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi-infected mice. https://doi.org/10.1101/2024.11.24.625079

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