NK Cells Dominate the Immunopathogenesis of Fatal Ehrlichiosis

Abstract

Human monocytic ehrlichiosis (HME) is a potentially lethal, tick‐transmitted infection caused by the obligately intracellular bacterium Ehrlichia chaffeensis. C57BL/6 mice model severe HME when infected with Ixodes ovatus Ehrlichia (IOE); they succumb to a toxic‐shock like syndrome mediated in part by TNF and CD8+ T cells and characterized by lymphopenia and by liver apoptosis and necrosis. CD4+ T cells mediate a protective IFN‐γresponse. The aim of this study was to compare the contribution of NK cells to that of T cells in the pathogenesis of ehrlichiosis. Flow cytometry was used to track splenic NK cells (NK1.1+, CD3−), NKT cells (NK1.1+, CD3+), T cells (CD3+, NK1.1−) and monocytes (CD11b+, NK1.1−) over the course of disease; these populations failed to expand but rather contracted before the animals’ death. Furthermore, splenic NK cells produced more IFN‐γ, TNF, granzyme B and Fas than did NKT or T cells. We depleted NK cells with anti‐asialo GM1 immune serum and observed reduced serum concentrations of IFN‐γ, TNF, and IL‐10 by ELISA, lower bacterial burdens in the spleen, liver, and lung by real‐time PCR, and attenuated liver injury by histopathology. Our data indicate that NK cells, rather than T cells, are the dominant contributors to the pathogenic immune response against IOE infection.