| First Author | Ismail N | Year | 2007 |
| Journal | Infect Immun | Volume | 75 |
| Issue | 9 | Pages | 4608-20 |
| PubMed ID | 17562770 | Mgi Jnum | J:123934 |
| Mgi Id | MGI:3719979 | Doi | 10.1128/IAI.00198-07 |
| Citation | Ismail N, et al. (2007) Relative importance of T-cell subsets in monocytotropic ehrlichiosis: a novel effector mechanism involved in ehrlichia-induced immunopathology in murine ehrlichiosis. Infect Immun 75(9):4608-20 |
| abstractText | 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. |
