title: Persistent infection contributes to heterologous protective immunity against fatal ehrlichiosis.
abstract: 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.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609, USA.
authors.forename: Nagaraja R
authors.initials: NR
authors.lastname: Thirumalapura
authors.forename: Emily C
authors.initials: EC
authors.lastname: Crossley
authors.forename: David H
authors.initials: DH
authors.lastname: Walker
authors.forename: Nahed
authors.initials: N
authors.lastname: Ismail
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D015704:CD4 Antigens / Q000032:analysis; D015169:Colony Count, Microbial; D004318:Doxycycline / Q000008:administration & dosage; D004536:Ehrlichia / Q000276:immunology*; D016873:Ehrlichiosis / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma; D004318:Doxycycline