title: Activation of invariant NKT cells by toll-like receptor 9-stimulated dendritic cells requires type I interferon and charged glycosphingolipids.
abstract: 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.
authors.affiliation: Institut National de la Recherche Médicale, U547, 59019 Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Paget
authors.forename: Thierry
authors.initials: T
authors.lastname: Mallevaey
authors.forename: Anneliese O
authors.initials: AO
authors.lastname: Speak
authors.forename: David
authors.initials: D
authors.lastname: Torres
authors.forename: Josette
authors.initials: J
authors.lastname: Fontaine
authors.forename: Kathleen C F
authors.initials: KC
authors.lastname: Sheehan
authors.forename: Monique
authors.initials: M
authors.lastname: Capron
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Christelle
authors.initials: C
authors.lastname: Faveeuw
authors.forename: Maria
authors.initials: M
authors.lastname: Leite de Moraes
authors.forename: Frances
authors.initials: F
authors.lastname: Platt
authors.forename: François
authors.initials: F
authors.lastname: Trottein
mesh_terms: D020384:Acidic Glycosphingolipids / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D016219:Immunotherapy, Adoptive; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000276:immunology / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism
chemical_list: D020384:Acidic Glycosphingolipids; D018949:Antigens, CD1; D055610:Antigens, CD1d; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D007371:Interferon-gamma