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

Lyme disease, caused byBorrelia 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 withB. burgdorferi, but only develop mild joint inflammation, was therefore examined.SLPI-deficient C57BL/6 mice challenged withB. burgdorferihad a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues ofB. burgdorferi-infectedSLPI-deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages.B. burgdorferi-infectedSLPI-deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (BActerialSelection toElucidateHost-microbeInteractions in highThroughput) library, we found that SLPI directly interacts withB. burgdorferi. These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.