Regulatory roles of CD1d-restricted NKT cells in the induction of toxic shock-like syndrome in an animal model of fatal ehrlichiosis

Heather Stevenson-Lerner, E. C. Crossley, N. Thirumalapura, David Walker, N. Ismail

Research output: Contribution to journalArticle

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Abstract

CD1d-restricted NKT cells are key players in host defense against various microbial infections. Using a murine model of fatal ehrlichiosis, we investigated the role of CD1d-restricted NKT cells in induction of toxic shock-like syndrome caused by gram-negative, lipopolysaccharide-lacking, monocytotropic Ehrlichia. Our previous studies showed that intraperitoneal infection of wild-type (WT) mice with virulent Ehrlichia (Ixodes ovatus Ehrlichia [IOE]) results in CD8+ T-cell-mediated fatal toxic shock-like syndrome marked by apoptosis of CD4+ T cells, a weak CD4+ Th1 response, overproduction of tumor necrosis factor alpha and interleukin-10, and severe liver injury. Although CD1d-/- mice succumbed to high-dose IOE infection similar to WT mice, they did not develop signs of toxic shock, as shown by elevated bacterial burdens, low serum levels of tumor necrosis factor, normal serum levels of liver enzymes, and the presence of few apoptotic hepatic cells. An absence of NKT cells restored the percentages and absolute numbers of CD4+ and CD8+ T cells and CD11b+ cells in the spleen compared to WT mice and was also associated with decreased expression of Fas on splenic CD4+ lymphocytes and granzyme B in hepatic CD8+ lymphocytes. Furthermore, our data show that NKT cells promote apoptosis of macrophages and up-regulation of the costimulatory molecule CD40 on antigen-presenting cells, including dendritic cells, B cells, and macrophages, which may contribute to the induction of pathogenic T-cell responses. In conclusion, our data suggest that NKT cells mediate Ehrlichia-induced T-cell-mediated toxic shock-like syndrome, most likely via cognate and noncognate interactions with antigen-presenting cells.

Original languageEnglish (US)
Pages (from-to)1434-1444
Number of pages11
JournalInfection and Immunity
Volume76
Issue number4
DOIs
StatePublished - Apr 2008

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Ehrlichia
Ehrlichiosis
Natural Killer T-Cells
Septic Shock
Animal Models
T-Lymphocytes
Ixodes
Antigen-Presenting Cells
CD40 Antigens
Liver
Tumor Necrosis Factor-alpha
Infection
Macrophages
Lymphocytes
Apoptosis
Granzymes
Serum
Interleukin-10
Dendritic Cells
Lipopolysaccharides

ASJC Scopus subject areas

  • Immunology

Cite this

Regulatory roles of CD1d-restricted NKT cells in the induction of toxic shock-like syndrome in an animal model of fatal ehrlichiosis. / Stevenson-Lerner, Heather; Crossley, E. C.; Thirumalapura, N.; Walker, David; Ismail, N.

In: Infection and Immunity, Vol. 76, No. 4, 04.2008, p. 1434-1444.

Research output: Contribution to journalArticle

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