Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids.

Christophe Paget (1) , Thierry Mallevaey (1) , Anneliese O Speak , David Torres (1) , Josette Fontaine (1) , Kathleen C F Sheehan , Monique Capron (1) , Bernhard Ryffel (2) , Christelle Faveeuw (1) , Maria Leite de Moraes , Frances Platt , François Trottein (1)

1 Schistosomiase, paludisme et inflammation
2 IEM - Immunologie et Embryologie Moléculaires

Invariant natural killer T (iNKT) cells are a subset of innate lymphocytes that recognize lipid antigens in the context of CD1d and mediate potent immune regulatory functions via the rapid production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). We investigated whether diverse Toll-like receptor (TLR) signals in myeloid dendritic cells (DCs) could differentially stimulate iNKT cells. Together with the lipopolysaccharide-detecting receptor TLR4, activation of the nucleic acid sensors TLR7 and TLR9 in DCs were particularly potent in stimulating iNKT cells to produce IFN-gamma, but not IL-4. iNKT cell activation in response to TLR9 stimulation required combined synthesis of type I interferon and de novo production of charged beta-linked glycosphingolipid(s) by DCs. In addition, DCs stimulated via TLR9 activated both iNKT cells and NK cells in vivo and protected mice against B16F10-induced melanoma metastases. These data underline the role of TLR9 in iNKT cell activation and might have relevance to infectious diseases and cancer.

Domaines: Immunologie

Christophe Paget, Thierry Mallevaey, Anneliese O Speak, David Torres, Josette Fontaine, et al.. Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids.. Immunity, 2007, 27 (4), pp.597-609. ⟨10.1016/j.immuni.2007.08.017⟩. ⟨hal-00317178⟩