An intradermal environment promotes a protective type-1 response against lethal systemic monocytotropic ehrlichial infection

Heather Stevenson-Lerner, Jeffrey M. Jordan, Ziad Peerwani, Hui Qun Wang, David Walker, Nahed Ismail

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Immune responses against monocytotropic ehrlichiosis during infection with a strain of Ehrlichia from Ixodes ovatus (IOE) were evaluated using a model that closely reproduces the pathology and immunity associated with tick-transmitted human monocytotropic ehrlichiosis. C57BL/6 mice were inoculated intradermally or intraperitoneally with high-dose highly virulent IOE or intraperitoneally with mildly virulent Ehrlichia muris. Intradermal (i.d.) infection with IOE established mild, self-limited disease associated with minimal hepatic apoptosis, and all mice survived past 30 days. Intraperitoneal (i.p.) infection with IOE resulted in acute, severe toxic shock-like syndrome and severe multifocal hepatic apoptosis and necrosis, and all mice succumbed to disease. Compared to i.p. infection with IOE, intradermally infected mice had a 100- to 1,000-fold lower bacterial load in the spleen with limited dissemination. Compared to mice infected intraperitoneally with IOE, i.d. infection stimulated a stronger protective type-1 cell-mediated response on day 7 of infection, characterized by increased percentages of both CD4+ and CD8 + splenic T cells, generation of a greater number of IOE-specific, gamma interferon-producing CD4+ Th1 cells, and higher levels of tumor necrosis factor (TNF-α) in the spleen but lower concentrations of serum TNF-α and interleukin-10. These data suggest that under the conditions of natural route of challenge (i.e., i.d. inoculation), the immune response has the capacity to confer complete protection against monocytotropic ehrlichiosis, which is associated with a strong cell-mediated type-1 response and decreased systemic production of pro- and anti-inflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)4856-4864
Number of pages9
JournalInfection and Immunity
Volume74
Issue number8
DOIs
StatePublished - Aug 2006

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Ixodes
Ehrlichiosis
Infection
Ehrlichia
Spleen
Tumor Necrosis Factor-alpha
Apoptosis
Th1 Cells
Bacterial Load
Liver
Ticks
Septic Shock
Inbred C57BL Mouse
Interleukin-10
Interferon-gamma
Immunity
Anti-Inflammatory Agents
Necrosis
Pathology
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

An intradermal environment promotes a protective type-1 response against lethal systemic monocytotropic ehrlichial infection. / Stevenson-Lerner, Heather; Jordan, Jeffrey M.; Peerwani, Ziad; Wang, Hui Qun; Walker, David; Ismail, Nahed.

In: Infection and Immunity, Vol. 74, No. 8, 08.2006, p. 4856-4864.

Research output: Contribution to journalArticle

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