title: Type I interferon production by plasmacytoid dendritic cells and monocytes is triggered by viruses, but the level of production is controlled by distinct cytokines.
abstract: The principal interferon-alpha/beta (IFN-I)-producing cells are plasmacytoid dendritic cell (PDC) precursors belonging to the lymphoid lineage. Monocytes that can differentiate into dendritic cells (DC) also produce IFN-I, although much less than PDC, after interaction with infectious agents. We show that whereas viruses trigger these cells to produce IFN-I, the amount of IFN is tightly controlled by cytokines. Monocytes produced IFN-I in response to Sendai virus (SV) infection, and PDC responded to both SV and herpes simplex virus (HSV). All cytokines tested failed to induce production of IFN-I in the absence of infection. However, among 18 relevant cytokines, incubation of PDC with interleukin-4 (IL-4), IL-15, and IL-7 alone or in combination with IL-3 before infection, enhanced IFN-I secretion. At variance, IL-12 alone or in synergy with granulocyte-macrophage colony-stimulating factor (GM-CSF) was active on SV-infected but not on HSV-infected monocytes. Tumor necrosis factor-alpha (TNF-alpha) and IL-4 inhibited IFN-I production by PDC and monocytes, respectively, and IL-10 strongly inhibited IFN-I production in both cell lineages. The response of PDC to IL-7 and IL-15, which also activate natural killer (NK) cell maturation, further emphasizes the cooperation between these two cell subsets in the control of innate immunity.
authors.affiliation: Laboratoire d'Immunologie, INSERM U 543, Hôpital Pitié-Salpêtrière, Université de Paris VI, 75013 Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gary-Gouy
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.forename: Ali H
authors.initials: AH
authors.lastname: Dalloul
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D004338:Drug Combinations; D004357:Drug Synergism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006561:Herpes Simplex / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D019409:Interleukin-15 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D010222:Parainfluenza Virus 1, Human / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D007370:Interferon Type I; D019409:Interleukin-15; D007377:Interleukin-3; D015851:Interleukin-7; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor