| First Author | Ronet C | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 2 | Pages | 899-908 |
| PubMed ID | 16002688 | Mgi Jnum | J:100672 |
| Mgi Id | MGI:3589291 | Doi | 10.4049/jimmunol.175.2.899 |
| Citation | Ronet C, et al. (2005) NKT cells are critical for the initiation of an inflammatory bowel response against Toxoplasma gondii. J Immunol 175(2):899-908 |
| abstractText | We demonstrated in this study the critical role of NKT cells in the lethal ileitis induced in C57BL/6 mice after infection with Toxoplasma gondii. This intestinal inflammation is caused by overproduction of IFN-gamma in the lamina propria. The implication of NKT cells was confirmed by the observation that NKT cell-deficient mice (Jalpha281(-/-)) are more resistant than C57BL/6 mice to the development of lethal ileitis. Jalpha281(-/-) mice failed to overexpress IFN-gamma in the intestine early after infection. This detrimental effect of NKT cells is blocked by treatment with alpha-galactosylceramide, which prevents death in C57BL/6, but not in Jalpha281(-/-), mice. This protective effect is characterized by a shift in cytokine production by NKT cells toward a Th2 profile and correlates with an increased number of mesenteric Foxp3 lymphocytes. Using chimeric mice in which only NKT cells are deficient in the IL-10 gene and mice treated with anti-CD25 mAb, we identified regulatory T cells as the source of the IL-10 required for manifestation of the protective effect of alpha-galactosylceramide treatment. Our results highlight the participation of NKT cells in the parasite clearance by shifting the cytokine profile toward a Th1 pattern and simultaneously to immunopathological manifestation when this Th1 immune response remains uncontrolled. |
