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Infection and Immunity, January 2009, p. 245-254, Vol. 77, No. 1
0019-9567/09/$08.00+0 doi:10.1128/IAI.00979-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Liver Transcriptome Profiles Associated with Strain-Specific Ehrlichia chaffeensis-Induced Hepatitis in SCID Mice 
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Department of Veterinary Biosciences, The Ohio State University, 1925 Coffey Rd., Columbus, Ohio 43210
Received 5 August 2008/ Returned for modification 8 September 2008/ Accepted 30 October 2008
Infection of humans with Ehrlichia chaffeensis, the etiologic agent of human monocytic ehrlichiosis, can cause hepatitis of various levels of severity. When the three human isolates of E. chaffeensis, each belonging to a different genogroup, are inoculated into severe combined immunodeficiency mice, the order of severity of clinical signs and bacterial burden detected in the liver is as follows (from greatest to least severity and highest to lowest burden): strain Wakulla, followed by strain Liberty, followed by strain Arkansas. In this article, we used microarray analysis to define transcriptional profiles characteristic of the histopathological features in the mouse liver. Cytokine and chemokine profiles and their receptor profiles were strikingly different among the three strains of E. chaffeensis: gamma interferon, CCL5, CXCL1, CXCL2, CXCL7, CXCL9, interleukin 2 receptor gamma (IL2R
), IL21R, CCR2, and CXCR6 were highly upregulated with strain Arkansas; and tumor necrosis factor (TNF), CCL2, CCL3, CCL5, CCL6, CCL12, CCL20, CXCL2, CXCL7, CXCL9, CXCL13, TNF receptor superfamily 9 (TNFRSF9), TNFRSF13β, IL1R2, IL2R, IL20Rβ, IL21R, CCR1, CCR2, and CXCR4 were highly upregulated with strain Wakulla. With strain Liberty, only CXCL13 was highly upregulated, and IL13R
2 was downregulated. In livers infected with the Arkansas strain, monocytes/macrophages and NK cells were enriched in the granulomas and an increase in NK cell marker mRNAs was detected. Livers infected with the Wakulla strain displayed infiltration of significantly more neutrophils and an increase in neutrophil marker mRNAs. Genes commonly upregulated in liver tissue infected with the three strains are other host innate immune and inflammatory response genes, including those encoding several acute-phase proteins. Genes downregulated commonly are related to host physiologic functions. The results suggest that marked modulation of host cytokine and chemokine profiles by E. chaffeensis strains underlies the distinct host liver disease.
* Corresponding author. Mailing address: The Ohio State University, Department of Veterinary Biosciences, 1925 Coffey Rd., Columbus, OH 43210. Phone: (614) 292-9677. Fax: (614) 292-6473. E-mail: rikihisa.1{at}osu.edu
Published ahead of print on 10 November 2008.
Supplemental material for this article may be found at http://iai.asm.org/.
Infection and Immunity, January 2009, p. 245-254, Vol. 77, No. 1
0019-9567/09/$08.00+0 doi:10.1128/IAI.00979-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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