scholarly journals Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

2007 ◽  
Vol 204 (6) ◽  
pp. 1359-1369 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Devi Banerjee ◽  
John Connolly ◽  
Anjli Kukreja ◽  
Elyana Matayeva ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Human Cancer ◽  
Gene Expression Pattern ◽  
Interferon Response ◽  
Type I ◽  
Fcγ Receptor ◽  
Selective Blockade ◽  
Mediated Effects ◽  
Novel Approach ◽  
Dc Maturation

The ability of dendritic cells (DCs) to activate immunity is linked to their maturation status. In prior studies, we have shown that selective antibody-mediated blockade of inhibitory FcγRIIB receptor on human DCs in the presence of activating immunoglobulin (Ig) ligands leads to DC maturation and enhanced immunity to antibody-coated tumor cells. We show that Fcγ receptor (FcγR)–mediated activation of human monocytes and monocyte-derived DCs is associated with a distinct gene expression pattern, including several inflammation-associated chemokines, as well as type 1 interferon (IFN) response genes, including the activation of signal transducer and activator of transcription 1 (STAT1). FcγR-mediated STAT1 activation is rapid and requires activating FcγRs. However, this IFN response is observed without a detectable increase in the expression of type I IFNs themselves or the need to add exogenous IFNs. Induction of IFN response genes plays an important role in FcγR-mediated effects on DCs, as suppression of STAT1 by RNA interference inhibited FcγR-mediated DC maturation. These data suggest that the balance of activating/inhibitory FcγRs may regulate IFN signaling in myeloid cells. Manipulation of FcγR balance on DCs and monocytes may provide a novel approach to regulating IFN-mediated pathways in autoimmunity and human cancer.

scholarly journals Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

2007 ◽  
Vol 204 (10) ◽  
pp. 2489-2489 ◽  
Author(s):  
Kavita M. Dhodapkar ◽  
Devi Banerjee ◽  
John Connolly ◽  
Anjli Kukreja ◽  
Elyana Matayeva ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Fcγ Receptor ◽  
Selective Blockade ◽  
Human Dendritic Cells

scholarly journals Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

2007 ◽  
Vol 204 (10) ◽  
pp. 2494-2494
Author(s):  
Kavita M. Dhodapkar ◽  
Devi Banerjee ◽  
John Connolly ◽  
Anjli Kukreja ◽  
Elyana Matayeva ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Fcγ Receptor ◽  
Selective Blockade ◽  
Human Dendritic Cells

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.

scholarly journals PACSIN1 regulates the TLR7/9-mediated type I interferon response in plasmacytoid dendritic cells

2012 ◽  
Vol 42 (3) ◽  
pp. 573-579 ◽  
Author(s):  
Eiji Esashi ◽  
Musheng Bao ◽  
Yi-Hong Wang ◽  
Wei Cao ◽  
Yong-Jun Liu
Keyword(s):  
Dendritic Cells ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
Interferon Response ◽  
Type I

scholarly journals Nonstructural Proteins 1 and 2 of Respiratory Syncytial Virus Suppress Maturation of Human Dendritic Cells

2008 ◽  
Vol 82 (17) ◽  
pp. 8780-8796 ◽  
Author(s):  
Shirin Munir ◽  
Cyril Le Nouen ◽  
Cindy Luongo ◽  
Ursula J. Buchholz ◽  
Peter L. Collins ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Fluorescent Protein ◽  
Nonstructural Protein ◽  
Type I ◽  
Ns1 Protein ◽  
Myeloid Dendritic Cells ◽  
Nonstructural Protein 1 ◽  
Syncytial Virus ◽  
Dc Maturation

ABSTRACT Human respiratory syncytial virus (RSV) is the most important agent of serious pediatric respiratory tract disease worldwide. One of the main characteristics of RSV is that it readily reinfects and causes disease throughout life without the need for significant antigenic change. The virus encodes nonstructural protein 1 (NS1) and NS2, which are known to suppress type I interferon (IFN) production and signaling. In the present study, we monitored the maturation of human monocyte-derived myeloid dendritic cells (DC) following inoculation with recombinant RSVs bearing deletions of the NS1 and/or NS2 proteins and expressing enhanced green fluorescent protein. Deletion of the NS1 protein resulted in increased expression of cell surface markers of DC maturation and an increase in the expression of multiple cytokines and chemokines. This effect was enhanced somewhat by further deletion of the NS2 protein, although deletion of NS2 alone did not have a significant effect. The upregulation was largely inhibited by pretreatment with a blocking antibody against the type I IFN receptor, suggesting that suppression of DC maturation by NS1/2 is, at least in part, a result of IFN antagonism mediated by these proteins. Therefore, this study identified another effect of the NS1 and NS2 proteins. The observed suppression of DC maturation may result in decreased antigen presentation and T-lymphocyte activation, leading to incomplete and/or weak immune responses that might contribute to RSV reinfection.

scholarly journals Fcγ Receptor Type I (CD64)-Mediated Impairment of the Capacity of Dendritic Cells to Activate Specific CD8 T Cells by IgG-opsonized Friend Virus

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 145 ◽  
Author(s):  
Zoltán Bánki ◽  
Roland Werner ◽  
Lydia Riepler ◽  
Annika Rössler ◽  
Brigitte Müllauer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Cytotoxic T Cell ◽  
Type I ◽  
Friend Virus ◽  
Fcγ Receptor ◽  
Fcγ Receptors ◽  
Viral Antigens ◽  
Antigen Presenting

Dendritic cells (DCs) express Fcγ receptors (FcγRs) for the binding immune complexes (ICs) consisting of IgG and antigens (Ags). IC–FcγR interactions have been demonstrated to enhance activation and antigen-presenting functions of DCs. Utilizing Friend virus (FV), an oncogenic mouse retrovirus, we investigated the effect of IgG-opsonization of retroviral particles on the infection of DCs and the subsequent presentation of viral antigens by DCs to virus-specific CD8 T cells. We found that opsonization by virus-specific non-neutralizing IgG abrogated DC infection and as a consequence significantly reduced the capacity of DCs to activate virus-specific CD8 T cells. Effects of IgG-opsonization were mediated by the high-affinity FcγR type I, CD64, expressed on DCs. Our results suggest that different opsonization patterns on the retroviral surface modulate infection and antigen-presenting functions of DCs, whereby, in contrast to complement, IgG reduces the capacity of DCs to activate cytotoxic T cell (CTL) responses.

Differential expression of type I interferon genes in plasmacytoid dendritic cells from HIV-infected patientss

2007 ◽  
Vol 30 (4) ◽  
pp. 84
Author(s):  
Martin D. Hyrcza ◽  
Sandy S. Der ◽  
Mario Ostrowski
Keyword(s):  
Dendritic Cells ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Cpg Dna ◽  
Ifn Alpha ◽  
Hiv Virus ◽  
Peripheral T Cells

Background: Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFN). Human genome contains thirteen IFN alpha genes and one IFN beta gene. Research in mice suggests that different IFNs are induced by different stimuli, but whether this is true in human cells is unknown. Patients with HIV-1 infection show chronic interferon response in peripheral T cells, which caused us to analyze the induction of the IFN alpha genes in their dendritic cells. Methods: Uninfected, acutely infected and long-term non-progressive donors were leukopheresed, following which pDCs were isolated by negative depletion. The dendritic cells were then treated for with one of the following: influenza virus, sendai virus, HIV virus, CpG DNA, imiquimod, or media alone, and the cells’ RNA was analysed by real time qPCR for changes in the RNA levels of four IFN alpha genes: α1, α2, α7, α8, as well as IFN beta. Results: Final results were not available at the time of abstract deposition.

scholarly journals Single-cell RNA-Seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells

2022 ◽  
Author(s):  
Flavien Brouiller ◽  
Francesca Nadalin ◽  
Ouardia Aït-Mohamed ◽  
Pierre-Emmanuel Bonté ◽  
Constance Delaugerre ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Type I ◽  
Rna Seq ◽  
Innate Response ◽  
Viral Response ◽  
Hiv 1 ◽  
Dc Maturation

Sensing of incoming viruses represents one of the pivotal tasks of dendritic cells (DC). Human primary blood DC encompass various subsets that are diverse in their susceptibility and response to HIV-1. The recent identification of Axl+DC, a new blood DC subset, endowed with unique capacities to bind, replicate, and transmit HIV-1 prompted us to evaluate its anti-viral response. We show that HIV-1 induced two main broad and intense transcriptional programs in different Axl+DC potentially induced by different sensors; a NF-κB-mediated program that led to DC maturation and efficient antigen-specific CD4+T cell activation, and a program mediated by STAT1/2 that activated type I IFN and an ISG response. These responses were absent from cDC2 exposed to HIV-1 except when viral replication occurred. Finally, Axl+DC actively replicating HIV-1 identified by quantification of viral transcripts exhibited a mixed NF-κB/ISG innate response. Our results suggest that the route of HIV-1 entry may dictate different innate sensing pathway by DC.

scholarly journals Human plasmacytoid dendritic cells elicit a Type I Interferon response by sensing DNA via the cGAS-STING signaling pathway

2016 ◽  
Vol 46 (7) ◽  
pp. 1615-1621 ◽  
Author(s):  
Christian Bode ◽  
Mario Fox ◽  
Poonam Tewary ◽  
Almut Steinhagen ◽  
Richard K. Ellerkmann ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Signaling Pathway ◽  
Type I Interferon ◽  
Plasmacytoid Dendritic Cells ◽  
Interferon Response ◽  
Type I
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