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* Institut National de la Santé et de la Recherche Médicale, Unité 547, Lille, France;
Institut Pasteur de Lille, Lille, France;
Université de Lille 2, Lille, France;
Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Villeneuve d’Ascq, France;
¶ Université des Sciences et Technologie de Lille I, Villeneuve d’Ascq, France;
|| Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, United Kingdom;
# Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8147, Institut de Recherche Necker Enfants Malades (Institut Fédératif de Recherche 94), Paris, France;
** Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France; and
Hôpital Necker, Paris, France
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-
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- 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.
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