Effect of complement component C3 deficiency on experimental Lyme Borreliosis in mice

Abstract

ABSTRACTMice deficient in complement component C3 (C3−/−) and syngeneic C57BL/6 control mice were challenged withBorrelia burgdorferito determine the role of complement in immune clearance and joint histopathology during experimental Lyme borreliosis. Tibiotarsal joint, ear, and heart tissues were monitored for spirochete numbers at 2, 4, 8, and 12 weeks postinoculation with 105B. burgdorferiB31 clone 5A4 by using quantitative real-time PCR. The spirochete load in joint and ear tissue remained higher in the C3−/−mice than in the wild-type counterparts throughout the 12-week study, whereas the numbers in heart tissue of both groups of mice decreased substantially at 8 to 12 weeks postinfection. Histopathology scores for joint tissue were generally higher in the C3−/−mice compared to C57BL/6 controls at 2 and 4 weeks postinfection, which may reflect the presence of higher numbers of bacteria in the joints at these early time points. Levels of anti-B. burgdorferiimmunoglobulin G tended to be reduced in the C3−/−mice compared to control mice. Furthermore, a 5.5-fold-lower number of the complement-sensitiveBorrelia gariniiwas needed to infect C3−/−mice compared to C57BL/6 mice, indicating that its sensitivity to complement is one barrier to infection of the mouse model byB. garinii. These results indicate that the complement system may be important in controlling the early dissemination and progression ofB. burgdorferiinfection.