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

被引:223
作者
Paget, Christophe
Mallevaey, Thierry
Speak, Anneliese O.
Torres, David
Fontaine, Josette
Sheehan, Kathleen C. F.
Capron, Monique
Ryffel, Bernhard
Faveeuw, Christelle
de Moraes, Maria Leite
Platt, Frances
Trottein, Francois [1 ]
机构
[1] Inst Natl Rech Med, U547, F-59019 Lille, France
[2] Inst Pasteur, F-59019 Lille, France
[3] Univ Lille 2, F-59019 Lille, France
[4] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England
[5] Washington Univ, Sch Med, St Louis, MO 63119 USA
[6] Univ Orleans, CNRS, UMR 6218, F-45071 Orleans, France
[7] Hop Necker Enfants Malad, Fac Med Rene Descartes Paris 5, CNRS, UMR 8147, F-75743 Paris, France
关键词
D O I
10.1016/j.immuni.2007.08.017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Invariant natural killer T (iNKT) cells area subset of innate lymphocytes that recognize lipid antigens in the context of CD1 d and mediate potent immune regulatory functions via the rapid production of interferon-gamma (IFN-y) 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 TLF19 in DCs were particularly potent in stimulating iNKT cells to produce IFN-y, 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 131 6F10-induced melanoma metastases. These data underline the role of TLR9 in iNKT cell activation and might have relevance to infectious diseases and cancer.
引用
收藏
页码:597 / 609
页数:13
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