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Infect. Immun. doi:10.1128/IAI.01127-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Differential Clearance and Immune Responses to Tick Cell vs. Macrophage Culture-Derived Ehrlichia chaffeensis in Mice

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Division of Biology, College of Arts and Sciences, Kansas State University, Manhattan, KS66506

^* To whom correspondence should be addressed. Email: rganta{at}vet.ksu.edu,

	Abstract

Human monocytic ehrlichiosis is caused by the tick transmitted rickettsia, Ehrlichia chaffeensis. We recently reported that E. chaffeensis grown in tick cells expresses different proteins than the bacteria grown in macrophages. Therefore, we tested the hypothesis that immune responses against E. chaffeensis would be different if 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 RT-PCR assay. Macrophage-grown E. chaffeensis was cleared in two 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 liver and spleen 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 IL-6 by peritoneal macrophages. The E. chaffeensis-specific IgG 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 cell or macrophage. 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 tick cell-specific Omp 14 gene to 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.

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