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Experimental infection of the mouse brain by a relapsing fever Borrelia species: a molecular analysis
D Cadavid1, V Bundoc, A G Barbour
1Department of Microbiology, University of Texas Health Science Center, San Antonio 78284-7758.
Abstract:
The spirochetal disease relapsing fever is notable not only for multiphasic antigenic variation but also for central neurologic manifestations. To further characterize involvement of the brain in this disorder, immunocompetent and -deficient mice were infected with Borrelia hermsii. Immunodeficient mice were treated while spirochetemic with neutralizing IgM monoclonal antibodies to the infecting serotype. Blood, cerebrospinal fluid, and brain tissue were examined by culture and polymerase chain reaction. In immunocompetent mice, antigenic variation occurred in the brain as well as in the blood. In immunodeficient mice, the infecting serotype was still present in the brain after it had been eliminated from the blood by the administered antibodies. These latter results cannot be accounted for by contamination of brain tissue and cerebrospinal fluid by blood and, hence, establish the direct involvement of the central nervous system in this experimental infection.
Insights
Relapsing fever involves central nervous system (CNS) manifestations. Borrelia hermsii infection in mice shows direct CNS involvement, with the bacteria persisting in the brain even after blood clearance.
Area of Science:
- Neuroscience
- Infectious Diseases
- Microbiology
Background:
- Relapsing fever, a spirochetal disease, exhibits antigenic variation and neurological symptoms.
- The direct involvement of the central nervous system (CNS) in Borrelia infections requires further characterization.
Purpose of the Study:
- To investigate the direct involvement of the brain in Borrelia hermsii infection.
- To characterize the behavior of Borrelia hermsii within the CNS of immunocompetent and immunodeficient mice.
Main Methods:
- Infection of immunocompetent and immunodeficient mice with Borrelia hermsii.
- Treatment of infected immunodeficient mice with neutralizing IgM monoclonal antibodies.
- Analysis of blood, cerebrospinal fluid (CSF), and brain tissue using culture and polymerase chain reaction (PCR).
Main Results:
- Antigenic variation of Borrelia hermsii was observed in both the blood and brain of immunocompetent mice.
- In immunodeficient mice, the infecting serotype persisted in the brain despite its elimination from the blood by antibody treatment.
- Results indicate direct CNS infection, ruling out blood contamination as the source of bacteria in CSF and brain tissue.
Conclusions:
- Borrelia hermsii directly invades and persists within the central nervous system.
- The brain serves as a sanctuary site for Borrelia hermsii, contributing to the neurological manifestations of relapsing fever.
- Experimental models demonstrate the capacity of spirochetes to evade antibody-mediated clearance within the CNS.
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