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.

Recognition of Borrelia burgdorferi, the Lyme Disease Spirochete, by TLR7 and TLR9 Induces a Type I IFN Response by Human Immune Cells

“…Differentiation of monocytes into mature mDCs results in the decline of surface expression of CD14; the CD14ϩCD11cϩ phenotype has been described as a transitional state in this maturation process (103,104,106,108). The results described here are supported by reports that isolated human monocytes and monocyte-derived mDCs, as well as mouse conventional DCs, produce IFN-␣ in response to microbial PAMPs (61,64,65,68,109,110). Although a similar study using isolated human CD14ϩ cells exposed to B. burgdorferi detected intense up-regulation of IFN-␤ transcript but only modest transcriptional induction of one IFN-␣ subtype (IFNA6) (77), it is recognized that pDC-derived type I IFN can prime human monocytes to become IFN-␣-producing cells (63,111).…”

“…Although pDCs have been classically described as high IFN-␣-producers, other cellular components of PBMCs have been documented to produce type I IFN (61)(62)(63)(64)(65). Flow cytometric analysis was used to identify the cell population(s) expressing IFN-␣ in response to B. burgdorferi.…”

Plasmacytoid dendritic cell‐induced migration and activation of NK cells in vivo

“…Since, activation of NK cells by pDC appeared to be indirect, we envisage that NK cells are in close contact with both pDC and cDC, and that IL15Ra on the cDC and molecules such as CD80/CD86 on the pDC may work co-operatively in activating the NK cells. A second possibility is that IL-15 released from cDC can bind to IL-15R on pDC [64], and then the pDC themselves may activate the NK cells. In our hands, the CpG-activated pDC seemed extremely potent at recruiting and activating NK cells.…”

Staphylococcus aureus-Induced Plasmacytoid Dendritic Cell Activation Is Based on an IgG-Mediated Memory Response

“…Although MyD88 (TLR)-independent pathways leading to pDC-derived type I IFN secretion have been described (11,16,17), in most cases viral infection has been demonstrated to activate pDC in a TLR7-or TLR9-dependent manner, being bound to the nature of the virus (18 -21). Thus, DNA viruses such as herpes simplex virus are thought to trigger a TLR9-dependent response, while ssRNA viruses such as influenza virus engage TLR7 (22)(23)(24)(25)(26)(27)(28).…”