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Exacerbated susceptibility to infection-stimulated immunopathology in CD1d-deficient mice.
Smiley, Stephen T; Lanthier, Paula A; Couper, Kevin N; Szaba, Frank M; Boyson, Jonathan E; Chen, Wangxue; Johnson, Lawrence L
Journal of immunology (Baltimore, Md. : 1950). 2005;174(12):7904-11.
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Abstract
Mice lacking functional CD1d genes were used to study mechanisms of resistance to the protozoan parasite Toxoplasma gondii. Wild-type (WT) BALB/c mice, CD1d-deficient BALB/c mice, and WT C57BL/6 mice all survived an acute oral infection with a low dose of mildly virulent strain ME49 T. gondii cysts. In contrast, most CD1d-deficient C57BL/6 mice died within 2 wk of infection. Despite having parasite burdens that were only slightly higher than WT mice, CD1d-deficient C57BL/6 mice displayed greater weight loss and intestinal pathology. In C57BL/6 mice, CD4(+) cells can cause intestinal pathology during T. gondii infection. Compared with WT mice, infected CD1d-deficient C57BL/6 mice had higher frequencies and numbers of activated (CD44(high)) CD4(+) cells in mesenteric lymph nodes. Depletion of CD4(+) cells from CD1d-deficient mice reduced weight loss and prolonged survival, demonstrating a functional role for CD4(+) cells in their increased susceptibility to T. gondii infection. CD1d-deficient mice are deficient in Valpha14(+) T cells, a major population of NKT cells. Involvement of these cells in resistance to T. gondii was investigated using gene-targeted Jalpha18-deficient C57BL/6 mice, which are deficient in Valpha14(+) T cells. These mice did not succumb to acute infection, but experienced greater weight loss and more deaths than B6 mice during chronic infection, indicating that Valpha14(+) cells contribute to resistance to T. gondii. The data identify CD4(+) cells as a significant component of the marked susceptibility to T. gondii infection observed in CD1d-deficient C57BL/6 mice, and establish T. gondii as a valuable tool for deciphering CD1d-dependent protective mechanisms.
Bibliographic metadata
- AI-46571, NIAID NIH HHS, United States
- AI-61587, NIAID NIH HHS, United States
- HL-72937, NHLBI NIH HHS, United States
- R01 HL072937-01, NHLBI NIH HHS, United States
- R01 HL072937-02, NHLBI NIH HHS, United States
- R01 HL072937-03, NHLBI NIH HHS, United States
- R01 HL072937-04, NHLBI NIH HHS, United States