Figure 1.

Cell-mediated pathogenic and protective responses in a model of fatal ehrlichiosis. Wild type C57BL/6 mice inoculated with virulent Ixodes Ovatus Ehrlichia (IOE) develop multi-organ failure and die between 8 and 10 days post-infection. Here we summarize protective and pathogenic mechanisms considering the cell-mediated immunity to Ehrlichia infection. Neutrophils migrate to infection site and induce strong pro-inflammatory response with hyperproduction of IL-1β, IL-6, IL-10, and chemokines. The role of neutrophils was also associated with induction of TNF-α-producing CD8 T cells that can either mediate organ damage or assist protective mechanisms. Another two important arms that mediate pathogenesis are the role of NK cells in eliminating infected cells in the target organs and the role of regulatory T cells (T regs), that end up shutting down protective mechanisms via IL-10. Protective mechanisms during infection by IOE include the induction of CD4 Th1 cells, that via IFN-γ activate on-site microbicidal functions of macrophages. NKT cells also play a role in stimulating such mechanism via IFN-γ.