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Relative importance of T-cell subsets in monocytotropic ehrlichiosis: a novel effector mechanism involved in Ehrlichia-induced immunopathology in murine ehrlichiosis.

Abstract：

:Infection with gram-negative monocytotropic Ehrlichia strains results in a fatal toxic shock-like syndrome characterized by a decreased number of Ehrlichia-specific CD4(+) Th1 cells, the expansion of tumor necrosis factor alpha (TNF-alpha)-producing CD8(+) T cells, and the systemic overproduction of interleukin-10 (IL-10) and TNF-alpha. Here, we investigated the role of CD4(+) and CD8(+) T cells in immunity to Ehrlichia and the pathogenesis of fatal ehrlichiosis caused by infection with low- and high-dose (10(3) and 10(5) bacterial genomes/mouse, respectively) ehrlichial inocula. The CD4(+) T-cell-deficient mice showed exacerbated susceptibility to a lethal high- or low-dose infection and harbored higher bacterial numbers than did wild-type (WT) mice. Interestingly, the CD8(+) T-cell-deficient mice were resistant to a low dose but succumbed to a high dose of Ehrlichia. The absence of CD8(+) T cells abrogated TNF-alpha and IL-10 production, reduced tissue injury and bacterial burden, restored splenic CD4(+) T-cell numbers, and increased the frequency of Ehrlichia-specific CD4(+) Th1 cells in comparison to infected WT mice. Although fatal disease is perforin independent, our data suggested that perforin played a critical role in controlling bacterial burden and mediating liver injury. Similar to WT mice, mortality of infected perforin-deficient mice was associated with CD4(+) T-cell apoptosis and a high serum concentration of IL-10. Depletion of IL-10 restored the number of CD4(+) and CD8(+) T cells in infected WT mice. Our data demonstrate a novel mechanism of immunopathology in which CD8(+) T cells mediate Ehrlichia-induced toxic shock, which is associated with IL-10 overproduction and CD4(+) T-cell apoptosis.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Ismail N,Crossley EC,Stevenson HL,Walker DH

doi

10.1128/IAI.00198-07

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

4608-20

issue

eissn

0019-9567

issn

1098-5522

pii

IAI.00198-07

journal_volume

pub_type

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Relative importance of T-cell subsets in monocytotropic ehrlichiosis: a novel effector mechanism involved in Ehrlichia-induced immunopathology in murine ehrlichiosis.