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Histologic, serologic, and molecular analysis of persistent ehrlichiosis in a murine model
Juan P Olano1, Gary Wen, Hui-Min Feng
1Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Abstract:
Human monocytotropic ehrlichiosis caused by Ehrlichia chaffeensis was reported in 1987. An animal model to study acute fatal ehrlichiosis in mice that has been developed closely resembles the fatal form of human monocytotropic ehrlichiosis. However, animal models for persistent infection in the genus Ehrlichia in immunocompetent mice have not been characterized. We report the histopathological progression of Ehrlichia muris infection in immunocompetent mice (AKR and C57BL/6 strains) correlated with their antibody response determined by indirect immunofluorescence and Western immunoblotting, and the distribution and quantity of the ehrlichial load by immunohistochemistry, polymerase chain reaction (PCR), and real-time PCR in lungs, liver, and spleen. Mild to moderate correlation was observed between histopathological grading in these organs and relative ehrlichial loads. The highest ehrlichial loads were present between days 4 and 14 after infection. E. muris was detected in tissues examined up to 150 days after infection by real-time PCR. Analysis of the serological response revealed several immunodominant antigens, including 200-, 180-, 100-, 73/75-, 45-, and 28-kd proteins. In conclusion, we have provided for the first time a complete histopathological, serological, immunohistochemical, and quantitative analysis of an animal model for the study of persistent ehrlichial infection.
Insights
This study characterizes a new animal model for persistent Ehrlichia muris infection in immunocompetent mice. The model reveals histopathological changes and antibody responses, aiding research into chronic ehrlichiosis.
Area of Science:
- Veterinary Pathology
- Immunology
- Microbiology
Background:
- Human monocytotropic ehrlichiosis (HME) caused by Ehrlichia chaffeensis emerged in 1987.
- Existing mouse models mimic acute fatal HME but lack characterization for persistent infections.
- Persistent Ehrlichia infections in immunocompetent hosts remain understudied.
Purpose of the Study:
- To establish and characterize an animal model for persistent Ehrlichia infection in immunocompetent mice.
- To analyze the histopathological progression, antibody response, and ehrlichial load.
- To provide a comprehensive analysis of a novel model for studying chronic ehrlichiosis.
Main Methods:
- Infection of AKR and C57BL/6 mice with Ehrlichia muris.
- Histopathological analysis of lungs, liver, and spleen.
- Serological analysis using indirect immunofluorescence and Western immunoblotting.
- Quantification of ehrlichial load via immunohistochemistry, PCR, and real-time PCR.
Main Results:
- Mild to moderate correlation between histopathology and ehrlichial load.
- Peak ehrlichial loads observed between days 4 and 14 post-infection.
- Ehrlichia muris detected in tissues up to 150 days post-infection.
- Identification of immunodominant antigens (200-, 180-, 100-, 73/75-, 45-, and 28-kd proteins).
Conclusions:
- A comprehensive histopathological, serological, and quantitative analysis of a persistent Ehrlichia muris infection model in mice was achieved.
- This model provides a valuable tool for studying chronic ehrlichial infections.
- The study identified key antigens involved in the host immune response to persistent Ehrlichia infection.
