The plasminogen activation system enhances brain and heart invasion in murine relapsing fever borreliosis

The role of the plasminogen activation system (PAS) was investigated during the course of infection of a relapsing fever Borrelia species in plasminog en-deficient (plg(-/-)) and control (plg(+/+) and plg(+/-)) mice. Subcutane ous inoculation of 10(4) spirochetes resulted in a peak spirochetemia five days after infection with 20-23 x 10(6) organisms per milliliter of whole b lood in all mice, indicating that the PAS had no effect on the development of this phase of the infection. Anemia, thrombocytopenia, hepatitis, cardit is, and splenomegaly were noted in all mice during and immediately after pe ak spirochetemia. Fibrin deposition in organs was noted in plg(-/-) mice bu t not in controls during these stages. Significantly greater spirochetal DN A burdens were consistently observed in the hearts and brains of control mi ce 28-30 days after infection, as determined by PCR amplification of this o rganism's flagellin gene (flaB), followed by quantitative densitometry. Fur thermore, the decreased spirochetal load in brains of plg(-/-) mice was ass ociated with a significant decrease in the degree of inflammation of the le ptomeninges in these mice. These findings indicate a role for the PAS in he art and brain invasion by relapsing fever Borrelia, resulting in organ inju ry.