Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells.
Among dendritic cells, plasmacytoid dendritic cells (PDC) represent a functionally distinct lineage. Regarding innate immunity, PDC secrete large amounts of type I IFN upon viral exposure or stimulation by microbial products such as unmethylated CpG-motif containing oligo-DNA due to their selective expression of TLR7 and TLR9. We asked whether they could acquire cytotoxic functions during the early phases of infection or after activation with TLR7 or TLR9 agonists. In the present study, we describe a human PDC cell line called GEN2.2, derived from leukemic PDC, that shares most of the phenotypic and functional features of normal PDC. We show that after contact with the influenza virus, GEN2.2, as well as normal PDC, acquires TRAIL and killer activity against TRAIL-sensitive target cells. Moreover, we show that activation of GEN2.2 cells by CpG-motif containing oligo-DNA or R848 also induces TRAIL and endows them with the ability to kill melanoma cells. Therefore, PDC may represent a major component of innate immunity that could participate to the clearance of infected cells and tumor cells. This phenomenon could be relevant for the efficacy of TLR7 or TLR9 agonists in the therapy of infectious disease and cancer.
Chaperot
Laurence
L
Department of Research and Development, Etablissement Français du Sang Rhône-Alpes Grenoble, La Tronche, France. laurence.chaperot@efs.sante.fr
Blum
Ariane
A
Manches
Olivier
O
Lui
Gabrielle
G
Angel
Juliette
J
Molens
Jean-Paul
JP
Plumas
Joël
J
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D018899:CpG Islands; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009975:Orthomyxoviridae / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha