Dendritic cells prime natural killer cells by trans-presenting interleukin 15.
Natural killer (NK) cells are important effector cells in the control of infections. The cellular and molecular signals required for NK cell activation in vivo remain poorly defined. By using a mouse model for the inducible ablation of dendritic cells (DCs), we showed that the in vivo priming of NK cell responses to viral and bacterial pathogens required the presence of CD11c(high) DCs. After peripheral Toll-like receptor (TLR) stimulation, NK cells were recruited to local lymph nodes, and their interaction with DCs resulted in the emergence of effector NK cells in the periphery. NK cell priming was dependent on the recognition of type I IFN signals by DCs and the subsequent production and trans-presentation of IL-15 by DCs to resting NK cells. CD11c(high) DC-derived IL-15 was necessary and sufficient for the priming of NK cells. Our data define a unique in vivo role of DCs for the priming of NK cells, revealing a striking and previously unappreciated homology to T lymphocytes of the adaptive immune system.
Lucas
Mathias
M
Skirball Institute of Biomolecular Medicine, Program in Molecular Pathogenesis, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Schachterle
William
W
Oberle
Karin
K
Aichele
Peter
P
Diefenbach
Andreas
A
D000818:Animals; D017951:Antigen Presentation; D039521:CD11c Antigen / Q000032:analysis; D045142:Cross-Priming; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology*; D007370:Interferon Type I; D019409:Interleukin-15 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011948:Receptors, Antigen, T-Cell; D015398:Signal Transduction
D039521:CD11c Antigen; D007370:Interferon Type I; D019409:Interleukin-15; D011948:Receptors, Antigen, T-Cell