TY - JOUR
T1 - Activation of Invariant NKT Cells by Toll-like Receptor 9-Stimulated Dendritic Cells Requires Type I Interferon and Charged Glycosphingolipids
AU - Paget, Christophe
AU - Mallevaey, Thierry
AU - Speak, Anneliese O.
AU - Torres, David
AU - Fontaine, Josette
AU - Sheehan, Kathleen C.F.
AU - Capron, Monique
AU - Ryffel, Bernhard
AU - Faveeuw, Christelle
AU - Leite de Moraes, Maria
AU - Platt, Frances
AU - Trottein, François
N1 - Funding Information:
This study was supported by Inserm, Institut Pasteur de Lille, Université de Lille 2, and l'Agence Nationale de la Recherche (program MIME, grant APV05103ESA). C.P. and T.M. were recipients of a doctoral fellowship from the Conseil Régional Nord Pas de Calais/Inserm and from the Ministère de l'Education Nationale de la Recherche et Technique, respectively, and D.T. was a recipient of a postdoctoral fellowship from the Conseil Régional Nord Pas de Calais/Inserm. A.O.S. was supported by a scholarship from the Glycobiology Institute, University of Oxford. C.F. is supported by Inserm and F.T., B.R., and M.L. de M. by the CNRS.
PY - 2007/10/26
Y1 - 2007/10/26
N2 - 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-γ (IFN-γ) 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-γ, 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 β-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.
AB - 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-γ (IFN-γ) 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-γ, 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 β-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.
KW - CELLIMMUNO
UR - https://www.scopus.com/pages/publications/35448936431
U2 - 10.1016/j.immuni.2007.08.017
DO - 10.1016/j.immuni.2007.08.017
M3 - Article
C2 - 17950005
AN - SCOPUS:35448936431
SN - 1074-7613
VL - 27
SP - 597
EP - 609
JO - Immunity
JF - Immunity
IS - 4
ER -