scholarly journals Human plasmacytoid dendritic cells are equipped with antigen-presenting and tumoricidal capacities

Blood ◽  
2012 ◽  
Vol 120 (19) ◽  
pp. 3936-3944 ◽  
Author(s):  
Jurjen Tel ◽  
Evelien L. Smits ◽  
Sébastien Anguille ◽  
Rubin N. Joshi ◽  
Carl G. Figdor ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Cell Subset ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Human Interferon ◽  
Target Cells ◽  
Type I ◽  
Dendritic Cell Subset ◽  
Antigen Presenting

Abstract Human plasmacytoid dendritic cells (pDCs) represent a highly specialized naturally occurring dendritic-cell subset and are the main producers of type I interferons (IFNs) in response to viral infections. We show that human pDCs activated by the preventive vaccine FSME specifically up-regulate CD56 on their surface, a marker that was thought to be specific for NK cells and associated with cytolytic effector functions. We observed that FSME-activated pDCs specifically lysed NK target cells and expressed cytotoxic molecules, such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and granzyme B. Elevated levels of these molecules coincided with the expression of CD56, indicative for skewing human pDCs toward an interferon-producing killer DC subset. Detailed phenotypical and functional analysis revealed that pDCs attained a mature phenotype, secreted proinflammatory cytokines, and had the capacity to present antigens and stimulate T cells. Here, we report on the generation of CD56+ human interferon producing killer pDCs with the capacity to present antigens. These findings aid in deciphering the role for pDCs in antitumor immunity and present a promising prospect of developing antitumor therapy using pDCs.

scholarly journals HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells

2019 ◽  
Author(s):  
Qi Wang ◽  
Li-Chung Tsao ◽  
Lei Lv ◽  
Yanping Xu ◽  
Liang Cheng ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Constitutive Expression ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Restriction Factors ◽  
Host Restriction ◽  
Host Restriction Factors ◽  
Hiv 1

AbstractPlasmacytoid dendritic cells (pDCs) are the major source of type I interferons (IFN-I) in rapid response to viral infections, with constitutive expression of interferon regulatory factor 7 (IRF7). HIV-1 expresses several accessory proteins to counteract specific IFN-induced host restriction factors. As one abundant virion-associated protein, HIV-1 Vpr remains enigmatic in enhancing HIV-1 infection via unclear mechanisms. Here we report that Vpr impaired IFN-I induction in pDCs to enhance HIV-1 replication in CD4+ T cells. Blockade of IFN-I signaling abrogated the effect of Vpr on HIV-1 replication. Virion-associated Vpr suppressed IFN-I induction in pDC by TLR7 agonists. Modulation of IFN-I induction by Vpr was genetically dependent on its activity of TET2 degradation. We further demonstrate that Vpr-mediated TET2 degradation reduced expression of IRF7 in pDCs. Finally, degradation of TET2 in pDCs by Vpr reduced the demethylation level of the IRF7 promoter via CXXC5-dependent recruitment. We conclude that HIV-1 Vpr functions to promote HIV-1 replication by suppressing TET2-dependent IRF7 expression and IFN-I induction in pDCs. The Vpr-TET2-IRF7 axis provides a novel therapeutic target to control HIV-1 infection.

scholarly journals Cell-intrinsic role for IFN-α–STAT1 signals in regulating murine Peyer patch plasmacytoid dendritic cells and conditioning an inflammatory response

Blood ◽  
2011 ◽  
Vol 118 (14) ◽  
pp. 3879-3889 ◽  
Author(s):  
Haiyan S. Li ◽  
Alexander Gelbard ◽  
Gustavo J. Martinez ◽  
Eiji Esashi ◽  
Huiyuan Zhang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Toll Like Receptor ◽  
Ccr9 Expression ◽  
A Cell ◽  
And Function ◽  
Antigen Presenting

Abstract Plasmacytoid dendritic cells (pDCs) reside in bone marrrow and lymphoid organs in homeostatic conditions and typically secrete abundant quantities of type I interferons (IFNs) on Toll-like receptor triggering. Recently, a pDC population was identified within Peyer patches (PPs) of the gut that is distinguished by its lack of IFN production; however, the relationship of PP pDCs to pDCs in other organs has been unclear. We report that PP pDCs are derived from common DC progenitors and accumulate in response to Fms-like tyrosine kinase 3 ligand, yet appear divergent in transcription factor profile and surface marker phenotype, including reduced E2-2 and CCR9 expression. Type I IFN signaling via STAT1 has a cell-autonomous role in accrual of PP pDCs in vivo. Moreover, IFN-α enhances pDC generation from DC progenitors by a STAT1-dependent mechanism. pDCs that have been developed in the presence of IFN-α resemble PP pDCs, produce inflammatory cytokines, stimulate Th17 cell generation, and fail to secrete IFN-α on Toll-like receptor engagement. These results indicate that IFN-α influences the development and function of pDCs by inducing emergence of an inflammatory (Th17-inducing) antigen-presenting subset, and simultaneously regulating accumulation of pDCs in the intestinal microenvironment.

scholarly journals Type I Interferon Production of Plasmacytoid Dendritic Cells under Control

2021 ◽  
Vol 22 (8) ◽  
pp. 4190
Author(s):  
Dóra Bencze ◽  
Tünde Fekete ◽  
Kitti Pázmándi
Keyword(s):  
Dendritic Cells ◽  
Viral Infections ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Tumor Resistance ◽  
Endogenous Factors ◽  
Associated Diseases ◽  
Type I Ifns

One of the most powerful and multifaceted cytokines produced by immune cells are type I interferons (IFNs), the basal secretion of which contributes to the maintenance of immune homeostasis, while their activation-induced production is essential to effective immune responses. Although, each cell is capable of producing type I IFNs, plasmacytoid dendritic cells (pDCs) possess a unique ability to rapidly produce large amounts of them. Importantly, type I IFNs have a prominent role in the pathomechanism of various pDC-associated diseases. Deficiency in type I IFN production increases the risk of more severe viral infections and the development of certain allergic reactions, and supports tumor resistance; nevertheless, its overproduction promotes autoimmune reactions. Therefore, the tight regulation of type I IFN responses of pDCs is essential to maintain an adequate level of immune response without causing adverse effects. Here, our goal was to summarize those endogenous factors that can influence the type I IFN responses of pDCs, and thus might serve as possible therapeutic targets in pDC-associated diseases. Furthermore, we briefly discuss the current therapeutic approaches targeting the pDC-type I IFN axis in viral infections, cancer, autoimmunity, and allergy, together with their limitations defined by the Janus-faced nature of pDC-derived type I IFNs.

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

The TLR-mediated response of plasmacytoid dendritic cells is positively regulated by estradiol in vivo through cell-intrinsic estrogen receptor α signaling

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 454-464 ◽  
Author(s):  
Cyril Seillet ◽  
Sophie Laffont ◽  
Florence Trémollières ◽  
Nelly Rouquié ◽  
Claude Ribot ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Genetic Ablation ◽  
17Β Estradiol ◽  
Female Host

Plasmacytoid dendritic cells (pDCs) produce large amounts of type I interferons (IFN-α/β) in response to viral or endogenous nucleic acids through activation of their endosomal Toll-like receptors (TLR-7 and TLR-9). Enhanced TLR-7–mediated IFN-α production by pDCs in women, compared with men, has been reported, but whether sex hormones, such as estrogens, are involved in this sex-based difference is unknown. Here we show, in humanized mice, that the TLR-7–mediated response of human pDCs is increased in female host mice relative to male. In a clinical trial, we establish that treatment of postmenopausal women with 17β-estradiol markedly enhances TLR-7– and TLR-9–dependent production of IFN-α by pDCs stimulated by synthetic ligands or by nucleic acid-containing immune complexes. In mice, we found exogenous and endogenous estrogens to promote the TLR-mediated cytokine secretion by pDCs through hematopoietic expression of estrogen receptor (ER) α. Genetic ablation of ERα gene in the DC lineage abrogated the enhancing effect of 17β-estradiol on their TLR-mediated production of IFN-α, showing that estrogens directly target pDCs in vivo. Our results uncover a previously unappreciated role for estrogens in regulating the innate functions of pDCs, which may account for sex-based differences in autoimmune and infectious diseases.

scholarly journals Sources of Type I Interferons in Infectious Immunity: Plasmacytoid Dendritic Cells Not Always in the Driver's Seat

2019 ◽  
Vol 10 ◽  
Author(s):  
Shafaqat Ali ◽  
Ritu Mann-Nüttel ◽  
Anja Schulze ◽  
Lisa Richter ◽  
Judith Alferink ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Type I ◽  
Infectious Immunity

Plasmacytoid dendritic cells and autoimmune inflammation

2014 ◽  
Vol 395 (3) ◽  
pp. 335-346 ◽  
Author(s):  
Georgina Galicia ◽  
Jennifer L. Gommerman
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Plasmacytoid Dendritic Cells ◽  
Type I ◽  
Toll Like Receptor ◽  
Autoimmune Encephalomyelitis ◽  
Effector Cells ◽  
The Central Nervous System ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Abstract Plasmacytoid dendritic cells (pDC) are a sub-population of dendritic cells (DC) that produce large amounts of type I interferon (IFN) in response to nucleic acids that bind and activate toll-like-receptor (TLR)9 and TLR7. Type I IFN can regulate the function of B, T, DC, and natural killer (NK) cells and can also alter the residence time of leukocytes within lymph nodes. Activated pDC can also function as antigen presenting cells (APC) and have the potential to prime and differentiate T cells into regulatory or inflammatory effector cells, depending on the context. In this review we discuss pDC ontogeny, function, trafficking, and activation. We will also examine how pDC can potentially be involved in regulating immune responses in the periphery as well as within the central nervous system (CNS) during multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE).

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