Journal
IMMUNITY
Volume 27, Issue 4, Pages 597-609Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2007.08.017
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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.
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