Immunopathology and ehrlichial propagation are regulated by interferon-gamma and interleukin-10 in a murine model of human granulocytic ehrlichiosis

Previous studies of human granulocytic ehrlichiosis (HGE) suggest a role fo r host immune response in resolving infection and in causing histopathologi cal lesions. We hypothesize that interferon (IFN)-gamma allows tissue injur y that is suppressed by interleukin (IL)-10 after initiation by ehrlichia i nfection. Thus, parental C57BL/6, IL-10-/-, and IFN-gamma-/- strains of mic e were infected and then assayed for hepatic histopathological lesions, ehr lichial burden, and cytokine responses to ehrlichial antigen in primary spl enic cultures during the first 21 days after infection. Histopathological s everity in C57/BLG and IL-10-/- mice rose in parallel through day 7, but th en diverged as pathology in IL-10-/- mice continued to increase and remaine d high throughout the course of the study. The histopathological rank of C5 7BL/6 of mice decreased at day 10 and returned to baseline levels at days 1 4 and 21, In contrast, the IFN-gamma-/-strain had baseline pathology scores throughout the course of the infection, yet had significantly higher ehrli chial burden both in the blood and tissues than C57BL/6 or IL-10-/- mice. T his suggests that histopathological lesions in the HGE murine model do not result from direct ehrlichia-mediated injury but from immunopathological me chanisms initiated by ehrlichial infection. The similarities with lesions i n humans suggest an, immunopathological basis for HGE.