Decorin-Deficient Mice Show Resistance To Lyme Disease
Borrelia burgdorferi is the causative agent of Lyme disease (LD). Microbial adhesion to and colonization of the infected host tissue is a critical step in the development of infection. B. burgdorferi may use decorin as a target for adherence and dissemination. Decorin is a small leucine-rich proteoglycan (SLRP) associated with collagen fibers found throughout the body. Using decorin-deficient mice (Dcn -/-), Brown, et al (J Clin Inv 107:845, 2001) examined the role of decorin in the development of LD.
Cultures of blood and tissue as well as and arthritis severity, were examined from Dcn -/-, Dcn +/-, and Dcn +/+ mice of both BALB/c and C3H/HeN background after needle inoculation and tick transmission of B. burgdorferi. Although not statistically significant, infected Dcn -/- mice consistently had a reduced percentage of Borrelia-positive blood cultures. Mice were sacrificed 14 days after infection to assess the dissemination of Borrelia in joints, heart, bladder and ear tissues. The percent of positive cultures for Borrelia was significantly reduced in Dcn -/- mice compared to Dcn +/- and Dcn +/+ mice. Only 47% of joints from Dcn -/- mice were Borrelia-positive compared to 90% of joints from Dcn +/+ mice (P<0.010). Histological evaluation revealed a significant reduction in both arthritis incidence and severity in Dcn -/- mice compared to Dcn +/+ (50% frequency with a 1.11 mean arthritis rating and 95% frequency with a 2.35 mean arthritis rating, respectively, P<0.001). Dcn -/- mice were more resistant to LD regardless of method of B. burgdorferi transmission.
These data demonstrate that decorin plays a role in the pathogenesis and dissemination of LD. When the dose of inoculum of Borrelia was increased, the differences in positive cultures disappeared presumably because the spirochetes utilized alternative non-decorin adhesion substrates. These data advance our understanding of the mechanism by which Borrelia disseminate after initial inoculum to skin.
