HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ronet, C. Articles by Buzoni-Gatel, D. Search for Related Content PubMed PubMed Citation Articles by Ronet, C. Articles by Buzoni-Gatel, D.

NKT Cells Are Critical for the Initiation of an Inflammatory Bowel Response against Toxoplasma gondii¹

Catherine Ronet^*, Sylvie Darche^*, Maria Leite de Moraes, Sachiko Miyake, Takashi Yamamura, Jacques A. Louis^*, Lloyd H. Kasper^2, and Dominique Buzoni-Gatel^2,3,*

^* Department of Parasitology, Unit of Early Responses to Intracellular Parasites and Immunopathology, Institut Pasteur-Institut National de la Recherche Agronomique, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche, University René Descartes, Paris V, Hôpital Necker, Paris, France; Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; and Departments of Medicine and Microbiology/Immunology, Dartmouth Medial School, Lebanon, NH 03756

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- in the lamina propria. The implication of NKT cells was confirmed by the observation that NKT cell-deficient mice (J281^–/–) are more resistant than C57BL/6 mice to the development of lethal ileitis. J281^–/– mice failed to overexpress IFN- in the intestine early after infection. This detrimental effect of NKT cells is blocked by treatment with -galactosylceramide, which prevents death in C57BL/6, but not in J281^–/–, 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 -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.

This article has been cited by other articles:

				D. V. Baev, S. Caielli, F. Ronchi, M. Coccia, F. Facciotti, K. E. Nichols, and M. Falcone Impaired SLAM-SLAM Homotypic Interaction between Invariant NKT Cells and Dendritic Cells Affects Differentiation of IL-4/IL-10-Secreting NKT2 Cells in Nonobese Diabetic Mice J. Immunol., July 15, 2008; 181(2): 869 - 877. [Abstract] [Full Text] [PDF]

				J. H. F. Pedra, J. Mattner, J. Tao, S. M. Kerfoot, R. J. Davis, R. A. Flavell, P. W. Askenase, Z. Yin, and E. Fikrig c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection Infect. Immun., January 1, 2008; 76(1): 308 - 316. [Abstract] [Full Text] [PDF]

				G. Wingender and M. Kronenberg Role of NKT cells in the digestive system. IV. The role of canonical natural killer T cells in mucosal immunity and inflammation Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G1 - G8. [Abstract] [Full Text] [PDF]

				S. Zeissig, A. Kaser, S. K. Dougan, E. E. S. Nieuwenhuis, and R. S. Blumberg Role of NKT Cells in the Digestive System. III. Role of NKT cells in intestinal immunity Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1101 - G1105. [Abstract] [Full Text] [PDF]

				L. D. Hazlett, Q. Li, J. Liu, S. McClellan, W. Du, and R. P. Barrett NKT Cells Are Critical to Initiate an Inflammatory Response after Pseudomonas aeruginosa Ocular Infection in Susceptible Mice J. Immunol., July 15, 2007; 179(2): 1138 - 1146. [Abstract] [Full Text] [PDF]

				M.-L. Michel, A. C. Keller, C. Paget, M. Fujio, F. Trottein, P. B. Savage, C.-H. Wong, E. Schneider, M. Dy, and M. C. Leite-de-Moraes Identification of an IL-17-producing NK1.1neg iNKT cell population involved in airway neutrophilia J. Exp. Med., May 14, 2007; 204(5): 995 - 1001. [Abstract] [Full Text] [PDF]

				T. Mallevaey, J. Fontaine, L. Breuilh, C. Paget, A. Castro-Keller, C. Vendeville, M. Capron, M. Leite-de-Moraes, F. Trottein, and C. Faveeuw Invariant and Noninvariant Natural Killer T Cells Exert Opposite Regulatory Functions on the Immune Response during Murine Schistosomiasis Infect. Immun., May 1, 2007; 75(5): 2171 - 2180. [Abstract] [Full Text] [PDF]

				R. R. Brutkiewicz CD1d Ligands: The Good, the Bad, and the Ugly J. Immunol., July 15, 2006; 177(2): 769 - 775. [Abstract] [Full Text] [PDF]

				I. Kawachi, J. Maldonado, C. Strader, and S. Gilfillan MR1-Restricted V{alpha}19i Mucosal-Associated Invariant T Cells Are Innate T Cells in the Gut Lamina Propria That Provide a Rapid and Diverse Cytokine Response J. Immunol., February 1, 2006; 176(3): 1618 - 1627. [Abstract] [Full Text] [PDF]