Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity.
Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central components of innate and adaptive immune responses. We describe here a third DC lineage, termed interferon-producing killer DCs (IKDCs), distinct from conventional DCs and plasmacytoid DCs and with the molecular expression profile of both NK cells and DCs. They produce substantial amounts of type I interferons (IFN) and interleukin (IL)-12 or IFN-gamma, depending on activation stimuli. Upon stimulation with CpG oligodeoxynucleotides, ligands for Toll-like receptor (TLR)-9, IKDCs kill typical NK target cells using NK-activating receptors. Their cytolytic capacity subsequently diminishes, associated with the loss of NKG2D receptor (also known as Klrk1) and its adaptors, Dap10 and Dap12. As cytotoxicity is lost, DC-like antigen-presenting activity is gained, associated with upregulation of surface major histocompatibility complex class II (MHC II) and costimulatory molecules, which formally distinguish them from classical NK cells. In vivo, splenic IKDCs preferentially show NK function and, upon systemic infection, migrate to lymph nodes, where they primarily show antigen-presenting cell activity. By virtue of their capacity to kill target cells, followed by antigen presentation, IKDCs provide a link between innate and adaptive immunity.
Chan
Camie W
CW
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, CRB-440, 1650 Orleans Street, Baltimore, Maryland 21231, USA.
Crafton
Emily
E
Fan
Hong-Ni
HN
Flook
James
J
Yoshimura
Kiyoshi
K
Skarica
Mario
M
Brockstedt
Dirk
D
Dubensky
Thomas W
TW
Stins
Monique F
MF
Lanier
Lewis L
LL
Pardoll
Drew M
DM
Housseau
Franck
F
D000222:Adaptation, Physiological; D000818:Animals; D017951:Antigen Presentation; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure; D015870:Gene Expression; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007372:Interferons / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000648:ultrastructure; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D007372:Interferons