Persistent infection contributes to heterologous protective immunity against fatal ehrlichiosis

Nagaraja R. Thirumalapura, Emily C. Crossley, David Walker, Nahed Ismail

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 β1 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.

Original languageEnglish (US)
Pages (from-to)5682-5689
Number of pages8
JournalInfection and Immunity
Volume77
Issue number12
DOIs
StatePublished - Dec 2009

Fingerprint

Heterologous Immunity
Ehrlichia
Ehrlichiosis
Ixodes
Doxycycline
Infection
Ehrlichia chaffeensis
Maintenance
T-Lymphocytes
Transforming Growth Factors
Ticks
Regulatory T-Lymphocytes
Inbred C57BL Mouse
Interferon-gamma
Spleen
Bacteria
Antigens

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Persistent infection contributes to heterologous protective immunity against fatal ehrlichiosis. / Thirumalapura, Nagaraja R.; Crossley, Emily C.; Walker, David; Ismail, Nahed.

In: Infection and Immunity, Vol. 77, No. 12, 12.2009, p. 5682-5689.

Research output: Contribution to journalArticle

Thirumalapura, Nagaraja R. ; Crossley, Emily C. ; Walker, David ; Ismail, Nahed. / Persistent infection contributes to heterologous protective immunity against fatal ehrlichiosis. In: Infection and Immunity. 2009 ; Vol. 77, No. 12. pp. 5682-5689.
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