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Infection and Immunity, January 2007, p. 135-145, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01127-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Differential Clearance and Immune Responses to Tick Cell-Derived versus Macrophage Culture-Derived Ehrlichia chaffeensis in Mice{triangledown} ,{dagger}

Roman R. Ganta,1* Chuanmin Cheng,1 Elizabeth C. Miller,2 Bridget L. McGuire,2 Lalitha Peddireddi,1 Kamesh R. Sirigireddy,1 and Stephen K. Chapes2

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine,1 Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, Kansas 665062

Received 18 July 2006/ Returned for modification 16 August 2006/ Accepted 2 October 2006

Human monocytic ehrlichiosis is caused by a tick-transmitted rickettsia, Ehrlichia chaffeensis. We recently reported that E. chaffeensis grown in tick cells expresses different proteins than bacteria grown in macrophages. Therefore, we tested the hypothesis that immune responses against E. chaffeensis would be different if the mice are challenged with bacteria grown in macrophages or tick cells. We assessed the E. chaffeensis clearance from the peritoneum, spleen, and liver by C57BL/6J mice using a TaqMan-based real-time reverse transcription-PCR assay. Macrophage-grown E. chaffeensis was cleared in 2 weeks from the peritoneum, whereas the pathogen from tick cells persisted for nine additional days and included three relapses of increasing bacterial load separated by three-day intervals. Tick cell-grown bacteria also persisted in the livers and spleens with higher bacterial loads compared to macrophage-grown bacteria and fluctuated over a period of 35 days. Three-day periodic cycles were detected in T-cell CD62L/CD44 ratios in the spleen and bone marrow in response to infections with both tick cell- and macrophage-grown bacteria and were accompanied by similar periodic cycles of spleen cell cytokine secretions and nitric oxide and interleukin-6 by peritoneal macrophages. The E. chaffeensis-specific immunoglobulin G response was considerably higher and steadily increased in mice infected with the tick cell-derived E. chaffeensis compared to DH82-grown bacteria. In addition, antigens detected by the immunoglobulins were significantly different between mice infected with the E. chaffeensis originating from tick cells or macrophages. The differences in the immune response to tick cell-grown bacteria compared to macrophage-grown bacteria reflected a delay in the shift of gene expression from the tick cell-specific Omp 14 gene to the macrophage-specific Omp 19 gene. These data suggest that the host response to E. chaffeensis depends on the source of the bacteria and that this experimental model requires the most natural inoculum possible to allow for a realistic understanding of host resistance.


* Corresponding author. Mailing address: Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave., Manhattan, KS 66506. Phone: (785) 532-4612. Fax: (785) 532-4851. E-mail: rganta{at}vet.ksu.edu.

{triangledown} Published ahead of print on 23 October 2006.

Editor: R. P. Morrison

{dagger} Kansas Agricultural Experiment Station contribution 06-269-J.


Infection and Immunity, January 2007, p. 135-145, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01127-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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