Delayed Clearance of Ehrlichia chaffeensis Infection in CD4 + T-Cell Knockout Mice†

Abstract

ABSTRACT Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis . To examine the role of helper T cells in host resistance to this macrophage-tropic bacterium, we assessed E. chaffeensis infections in three mouse strains with differing functional levels of helper T cells. Wild-type, C57BL/6J mice resolved infections in approximately 2 weeks. Major histocompatibility complex class II (MHCII) knockout, B6.129- Abb tm1 mice lacking helper T cells developed persistent infections that were not resolved even after several months. CD4 + T-cell-deficient, B6.129S6- Cd4 tm1Knw mice cleared the infection, but the clearance took 2 weeks longer than it did for wild-type mice. C57BL/6J mice resolved infection more rapidly following a second experimental challenge, but B6.129S6- Cd4 tm1Knw mice did not. The B6.129S6- Cd4 tm1Knw mice also developed active E. chaffeensis -specific immunoglobulin G responses that were slightly lower in concentration and slower to develop than that observed in C57BL/6J mice. E. chaffeensis -specific cytotoxic T cells were not detected following a single bacterial challenge in any mouse strain, including wild-type C57BL/6J mice. However, the cytotoxic T-cell activity developed in all three mouse strains, including the MHCII and CD4 + T-cell knockouts, when challenged with a second E. chaffeensis infection. The data reported here suggest that the cell-mediated immunity, orchestrated by CD4 + T cells is critical for conferring rapid clearance of E. chaffeensis .