Pathology, immunohistology, and cytokine responses in early phases of human granulocytic ehrlichiosis in a murine model

Human granulocytic ehrlichiosis (HGE) results in fever, pancytopenia, and m ild liver injury, We used a mouse model to examine immunity in the pathogen esis of HGE, HGE agent-infected C3H/HeJ mice were necropsied over 21 days. Histologic, immunohistologic, and serologic analyses, blood culture, tissue and blood polymerase chain reaction (PCR), cell counts, serum chemistries, and plasma cytokine ELISAs were performed, No clinical signs were detected . Ehrlichiae were identified in neutrophils in hematopoietic tissues maxima lly on day 7, Interleukin (IL)-10 levels were high throughout, whereas inte rferon (IFN)-gamma levels peaked on days 7 and 10 and dropped thereafter. H epatic lymphohistiocytic aggregates with apoptoses were maximal at day 14, HGE-agent infection of mice induces pathologic changes similar to those in infected humans, despite differences in cytokine profile. The IFN-gamma pea k prior to maximal pathologic change, when ehrlichiae are absent in tissues , suggests a role for host immunity in the pathogenesis of HGE.