Project description:Infection of humans with Ehrlichia chaffeensis, the etiologic agent of human monocytic ehrlichiosis, can cause hepatitis of varying severity. When the three human isolates of E. chaffeensis, each belongs to different geno-groups, are inoculated into severe combined immunodeficiency mice, the severity of clinical signs and bacterial burden detected in the liver are strain Wakulla>Liberty>Arkansas. Disseminated and granulomatous inflammation is evident in the liver of mice infected with strains Wakulla and Arkansas, respectively, but not in mice infected with strain Liberty. In this paper, we used microarray analysis to define transcriptional profiles characteristic to the histopathological features in the mouse liver. Cytokine and chemokine profiles were strikingly different among three strains of E. chaffeensis: IFN-γ, CCL5, CXCL1, CXCL2, CXCL7 and CXCL9 were highly up-regulated with strain Arkansas, TNF-α, CCL2, CCL3, CCL5, CCL6, CCL12, CCL20, CXCL2, CXCL7, CXCL9 and CXCL13 were highly up-regulated with strain Wakulla. With strain Liberty, only CXCL13 was highly up-regulated. In the livers infected with the Arkansas strain, monocytes/macrophages and NK cells were enriched in the granulomas and increase of NK cell-marker mRNAs was detected. Livers infected with the Wakulla strain displayed infiltration of significantly more neutrophils and increase of neutrophil-marker mRNAs. Genes up-regulated commonly in the liver infected with the three stains are other host innate immune and inflammatory response genes including several acute phase proteins. Genes down-regulated commonly are related to host physiologic functions. The results suggest that marked modulation of host cytokine and chemokine profiles by E. chaffeensis strains underlie the distinct host liver disease.
Project description:Ehrlichia chaffeensis is an obligately intracellular bacterium that establishes infection in mononuclear phagocytes through largely undefined reprogramming strategies. Recently, E. chaffeensis effectors Ank200, TRP120, and TRP32 have been shown to function as nucleomodulins that enter the host nucleus and directly modulate transcription of genes implicated in cellular processes such as transcription regulation, apoptosis, phosphorylation, and immune cell activation. In this study, we found that E. chaffeensis TRP47 enters the host cell nucleus and binds regulatory regions of multiple host genes relevant to infection.
