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

Nahed Ismail, Emily C. Crossley, Heather Stevenson-Lerner, David Walker

Research output: Contribution to journalArticle

28 Scopus citations

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-α)-producing CD8+ T cells, and the systemic overproduction of interleukin-10 (IL-10) and TNF-α. 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 (103 and 105 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-α 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.

Original languageEnglish (US)
Pages (from-to)4608-4620
Number of pages13
JournalInfection and Immunity
Volume75
Issue number9
DOIs
StatePublished - Sep 2007

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ASJC Scopus subject areas

  • Immunology

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