Delayed invasion of the kidney and brain by Borrelia crocidurae in plasminogen-deficient mice

Borrelia crocidurae is an etiologic agent of relapsing fever in Africa and is transmitted to humans by the bite of soft ticks of the genus Ornithodoro s. The role of the plasminogen (Plg) activation system for the pathogenicit y of B. crocidurae was investigated by infection of Plg-deficient (plg(-/-) ) and Plg wild-type (plg(+/+)) mice. No differences in spirochetemia were o bserved between the plg(-/-) and plg(+/+) mice. However, signs indicative o f brain invasion, such as neurological symptoms and/or histopathological ch anges, were more common in plg(+/+) mice. Quantitative immunohistochemical analysis demonstrated infection of spirochetes in kidney interstitium and b rain as soon as 2 days postinoculation. Lower numbers of extravascular spir ochetes in plg(-/-) mice during the first days of infection suggested a les s efficient invasion mechanism in these mice than in the plg(+/+) mice. The invasion of the kidneys in plg(-/-) mice produced no significant inflammat ion, as seen by quantitative immunohistochemistry of the CD45 common leukoc yte marker. However, significant kidney inflammation was observed with infe ction in the plg(+/+) mice. In brain, inflammation was more severe in plg(/+) mice than in plg(-/-) mice, and the numbers of CD45(+) cells increased significantly with duration of infection in the plg(+/+) mice. The results show that invasion of brain and kidney occurs as early as 2 days after inoc ulation. Also, Plg is not required for establishment of spirochetemia by th e organism, whereas it is involved in the invasion of organs.