Secretory leukocyte protease inhibitor influences periarticular joint inflammation in <i>Borrelia burgdorferi</i>-infected mice.

Abstract

Lyme disease, caused by <i>Borrelia burgdorferi</i>, 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 <i>B. burgdorferi</i> but only develop mild joint inflammation, was therefore examined. <i>Slpi</i>-deficient C57BL/6 mice challenged with <i>B. burgdorferi</i> 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 <i>B. burgdorferi-</i>infected <i>Slpi</i>-deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. <i>B. burgdorferi</i>-infected <i>Slpi</i>-deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT (<b>BA</b>cterial <b>S</b>election to <b>E</b>lucidate <b>H</b>ost-microbe <b>I</b>nteractions in high <b>T</b>hroughput) library, we found that SLPI directly interacts with <i>B. burgdorferi</i>. These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.