Delayed Invasion of the Kidney and Brain by Borrelia crocidurae in Plasminogen-Deficient Mice

Abstract

ABSTRACT 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 Ornithodoros . The role of the plasminogen (Plg) activation system for the pathogenicity of B. crocidurae was investigated by infection of Plg-deficient ( plg −/− ) and Plg wild-type ( plg +/+ ) mice. No differences in spirochetemia were observed between the plg −/− and plg +/+ mice. However, signs indicative of brain invasion, such as neurological symptoms and/or histopathological changes, were more common in plg +/+ mice. Quantitative immunohistochemical analysis demonstrated infection of spirochetes in kidney interstitium and brain as soon as 2 days postinoculation. Lower numbers of extravascular spirochetes in plg −/− mice during the first days of infection suggested a less efficient invasion mechanism in these mice than in the plg +/+ mice. The invasion of the kidneys in plg −/− mice produced no significant inflammation, as seen by quantitative immunohistochemistry of the CD45 common leukocyte marker. However, significant kidney inflammation was observed with infection 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 inoculation. Also, Plg is not required for establishment of spirochetemia by the organism, whereas it is involved in the invasion of organs.