Human monocytotropic
ehrlichiosis (HME), an emerging and often life-threatening tick-transmitted disease, is caused by the obligately intracellular bacterium Ehrlichia chaffeensis. HME is modeled in C57BL/6 mice using Ehrlichia muris, which causes
persistent infection, and Ixodes ovatus Ehrlichia (IOE), which is either acutely lethal or sublethal depending on the dose and route of inoculation. A persistent primary E. muris
infection, but not a sublethal IOE
infection, protects mice against an ordinarily lethal secondary IOE challenge. In the present study, we determined the role of
persistent infection in maintenance of protective memory immune responses. E. muris-infected mice were treated with
doxycycline or left untreated and then challenged with an ordinarily lethal dose of IOE. Compared to E. muris-primed mice treated with
doxycycline, untreated mice persistently infected with E. muris had significantly greater numbers of
antigen-specific
gamma interferon-producing splenic memory T cells, significant expansion of CD4(+) CD25(+) T regulatory cells, and production of
transforming growth factor beta1 in the spleen. Importantly, E. muris-primed mice treated with
doxycycline showed significantly greater susceptibility to challenge
infection with IOE compared to untreated mice persistently infected with E. muris. The study indicated that persistent ehrlichial
infection contributes to heterologous protection by stimulating the maintenance of memory T-cell responses.