TY - JOUR
T1 - Pathology, immunohistology, and cytokine responses in early phases of human granulocytic ehrlichiosis in a murine model
AU - Martin, Mary E.
AU - Bunnell, Joseph E.
AU - Dumler, J. Stephen
N1 - Funding Information:
Financial support: Grant RO1 AI 41213-01 from the National Institutes of Allergy and Infectious Diseases.
PY - 2000
Y1 - 2000
N2 - Human granulocytic ehrlichiosis (HGE) results in fever, pancytopenia, and mild liver injury. We used a mouse model to examine immunity in the pathogenesis 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 maximally on day 7. Interleukin (IL)-10 levels were high throughout, whereas interferon (IFN)-γ levels peaked on days 7 and 10 and dropped thereafter. Hepatic 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-γ peak prior to maximal pathologic change, when ehrlichiae are absent in tissues, suggests a role for host immunity in the pathogenesis of HGE.
AB - Human granulocytic ehrlichiosis (HGE) results in fever, pancytopenia, and mild liver injury. We used a mouse model to examine immunity in the pathogenesis 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 maximally on day 7. Interleukin (IL)-10 levels were high throughout, whereas interferon (IFN)-γ levels peaked on days 7 and 10 and dropped thereafter. Hepatic 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-γ peak prior to maximal pathologic change, when ehrlichiae are absent in tissues, suggests a role for host immunity in the pathogenesis of HGE.
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U2 - 10.1086/315206
DO - 10.1086/315206
M3 - Article
C2 - 10608792
AN - SCOPUS:0033967255
SN - 0022-1899
VL - 181
SP - 374
EP - 378
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -