Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity

Camie W Chan¹, Emily Crafton¹, Hong-Ni Fan¹, James Flook¹, Kiyoshi Yoshimura¹, Mario Skarica¹, Dirk Brockstedt², Thomas W Dubensky², Monique F Stins³, Lewis L Lanier⁴, Drew M Pardoll¹ & Franck Housseau¹

¹  Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, CRB-440, 1650 Orleans Street, Baltimore, Maryland 21231, USA.

²  Cerus Corporation, 2411 Stanwell Drive, Concord, California 94520, USA.

³  Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins University Medical School, 720 Rutland Avenue, Ross 1170, Baltimore, Maryland 21205, USA.

⁴  Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, 513 Parnassus Avenue, HSE 420, San Francisco, California 94143, USA.

Natural killer (NK) cells and dendritic cells (DCs) are, respectively, central components of innate and adaptive immune responses^{1, 2}. 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-, 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.

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