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Activation of invariant NKT cells by the helminth parasite schistosoma mansoni.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2006 Feb 15; Vol. 176 (4), pp. 2476-85. - Publication Year :
- 2006
-
Abstract
- Mouse CD1d-restricted NKT cells, including invariant (i)NKT cells, are innate cells activated by glycolipid Ags and play important roles in the initiation and regulation of immune responses. Through their ability to promptly produce large amounts of Th1 and/or Th2 cytokines upon TCR engagement, iNKT cells exert crucial functions in the immune/inflammatory system during bacterial, protozoan, fungal, and viral infections. However, their roles during metazoan parasite infection, which are generally associated with strong Th2 responses, still remain elusive. In this study, we show that during the course of murine schistosomiasis, iNKT cells exhibit an activated phenotype and that following schistosome egg encounter in the liver, hepatic iNKT cells produce both IFN-gamma and IL-4 in vivo. We also report that schistosome egg-sensitized dendritic cells (DCs) activate, in a CD1d-dependent manner, iNKT cells to secrete IFN-gamma and IL-4 in vitro. Interestingly, transfer of egg-sensitized DCs promotes a strong Th2 response in recipient wild-type mice, but not in mice that lack iNKT cells. Engagement of TLRs in DCs is not necessary for iNKT cell stimulation in response to egg-sensitized DCs, suggesting an alternative pathway of activation. Finally, we propose that self, rather than parasite-derived, CD1d-restricted ligands are implicated in iNKT cell stimulation. Taken together, our data show for the first time that helminths can activate iNKT cells to produce immunoregulatory cytokines in vivo, enabling them to influence the adaptive immune response.
- Subjects :
- Animals
Antigens, CD1 immunology
Antigens, CD1 metabolism
Antigens, CD1d
Cells, Cultured
Dendritic Cells immunology
Dendritic Cells metabolism
Female
Killer Cells, Natural cytology
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
Ligands
Mice
Mice, Inbred C57BL
Ovum
Receptors, Antigen, T-Cell immunology
T-Lymphocytes, Regulatory cytology
T-Lymphocytes, Regulatory metabolism
Th2 Cells immunology
Lymphocyte Activation immunology
Parasites immunology
Schistosoma mansoni immunology
Schistosomiasis mansoni immunology
Schistosomiasis mansoni parasitology
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 176
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 16456008
- Full Text :
- https://doi.org/10.4049/jimmunol.176.4.2476