scholarly journals Virus-induced Interferon α Production by a Dendritic Cell Subset in the Absence of Feedback Signaling In Vivo

2002 ◽  
Vol 195 (4) ◽  
pp. 507-516 ◽  
Author(s):  
Winfried Barchet ◽  
Marina Cella ◽  
Bernhard Odermatt ◽  
Carine Asselin-Paturel ◽  
Marco Colonna ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Marginal Zone ◽  
Viral Infections ◽  
Cell Subset ◽  
Interferon Α ◽  
Type I ◽  
Dendritic Cell Subset ◽  
Type I Ifn ◽  
High Level

An effective type I interferon (IFN-α/β) response is critical for the control of many viral infections. Here we show that in vesicular stomatitis virus (VSV)-infected mouse embryonic fibroblasts (MEFs) the production of IFN-α is dependent on type I IFN receptor (IFNAR) triggering, whereas in infected mice early IFN-α production is IFNAR independent. In VSV-infected mice type I IFN is produced by few cells located in the marginal zone of the spleen. Unlike other dendritic cell (DC) subsets, FACS®-sorted CD11cintCD11b−GR-1+ DCs show high IFN-α expression, irrespective of whether they were isolated from VSV-infected IFNAR-competent or -deficient mice. Thus, VSV preferentially activates a specialized DC subset presumably located in the marginal zone to produce high-level IFN-α largely independent of IFNAR feedback signaling.

Spi-B is critical for plasmacytoid dendritic cell function and development

Blood ◽  
2012 ◽  
Vol 120 (24) ◽  
pp. 4733-4743 ◽  
Author(s):  
Izumi Sasaki ◽  
Katsuaki Hoshino ◽  
Takahiro Sugiyama ◽  
Chihiro Yamazaki ◽  
Takahiro Yano ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dendritic Cell ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Plasmacytoid Dendritic Cell ◽  
Cell Subset ◽  
Type I ◽  
Dendritic Cell Subset ◽  
Type I Ifn ◽  
Deficient Mice

Abstract Plasmacytoid dendritic cells (pDCs), originating from hematopoietic progenitor cells in the BM, are a unique dendritic cell subset that can produce large amounts of type I IFNs by signaling through the nucleic acid–sensing TLR7 and TLR9 (TLR7/9). The molecular mechanisms for pDC function and development remain largely unknown. In the present study, we focused on an Ets family transcription factor, Spi-B, that is highly expressed in pDCs. Spi-B could transactivate the type I IFN promoters in synergy with IFN regulatory factor 7 (IRF-7), which is an essential transcription factor for TLR7/9-induced type I IFN production in pDCs. Spi-B–deficient pDCs and mice showed defects in TLR7/9-induced type I IFN production. Furthermore, in Spi-B–deficient mice, BM pDCs were decreased and showed attenuated expression of a set of pDC-specific genes whereas peripheral pDCs were increased; this uneven distribution was likely because of defective retainment of mature nondividing pDCs in the BM. The expression pattern of cell-surface molecules in Spi-B–deficient mice indicated the involvement of Spi-B in pDC development. The developmental defects of pDCs in Spi-B–deficient mice were more prominent in the BM than in the peripheral lymphoid organs and were intrinsic to pDCs. We conclude that Spi-B plays critical roles in pDC function and development.

scholarly journals Endogenous mitochondrial double‐stranded RNA is not an activator of the type I interferon response in human pancreatic beta cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexandra Coomans de Brachène ◽  
Angela Castela ◽  
Anyïshai E. Musuaya ◽  
Lorella Marselli ◽  
Piero Marchetti ◽  
...  
Keyword(s):  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Viral Infections ◽  
Human Islets ◽  
Interferon Response ◽  
Interferon Α ◽  
Type I ◽  
Type I Ifn ◽  
Danger Signal ◽  
Double Stranded Rna

Abstract Background Type 1 diabetes (T1D) is an autoimmune disease characterized by the progressive destruction of pancreatic beta cells. Interferon-α (IFNα), an antiviral cytokine, is expressed in the pancreatic islets in early T1D, which may be secondary to viral infections. However, not all patients harboring a type I IFN signature present signals of viral infection, suggesting that this response might be initiated by other “danger signals”. Accumulation of mitochondrial double-stranded RNA (mtdsRNA; a danger signal), secondary to silencing of members of the mitochondrial degradosome, PNPT1 and SUV3, has been described to activate the innate immune response. Methods To evaluate whether mtdsRNA represents a “danger signal” for pancreatic beta cells in the context of T1D, we silenced PNPT1 and/or SUV3 in slowly proliferating human insulin-secreting EndoC-βH1 cells and in non-proliferating primary human beta cells and evaluated dsRNA accumulation by immunofluorescence and the type I IFN response by western blotting and RT-qPCR. Results Only the simultaneous silencing of PNPT1/SUV3 induced dsRNA accumulation in EndoC-βH1 cells but not in dispersed human islets, and there was no induction of a type I IFN response. By contrast, silencing of these two genes individually was enough to induce dsRNA accumulation in fibroblasts present in the human islet preparations. Conclusions These data suggest that accumulation of endogenous mtdsRNA following degradosome knockdown depends on the proliferative capacity of the cells and is not a mediator of the type I IFN response in human pancreatic beta cells.

scholarly journals HIV-1 Nef Protein Affects Cytokine and Extracellular Vesicles Production in the GEN2.2 Plasmacytoid Dendritic Cell Line

Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 74
Author(s):  
Alessandra Aiello ◽  
Flavia Giannessi ◽  
Zulema Antonia Percario ◽  
Katia Fecchi ◽  
Claudia Arenaccio ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cell Line ◽  
Plasmacytoid Dendritic Cell ◽  
Cell Subset ◽  
Extracellular Vesicle ◽  
Type I ◽  
Dendritic Cell Subset ◽  
System A ◽  
New Information ◽  
Tnf Α

Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset specialized in type I interferon production, whose role in Human Immunodeficiency Virus (HIV) infection and pathogenesis is complex and not yet well defined. Considering the crucial role of the accessory protein Nef in HIV pathogenicity, possible alterations in intracellular signalling and extracellular vesicle (EV) release induced by exogenous Nef on uninfected pDCs have been investigated. As an experimental model system, a human plasmacytoid dendritic cell line, GEN2.2, stimulated with a myristoylated recombinant NefSF2 protein was employed. In GEN2.2 cells, Nef treatment induced the tyrosine phosphorylation of STAT-1 and STAT-2 and the production of a set of cytokines, chemokines and growth factors including IP-10, MIP-1β, MCP-1, IL-8, TNF-α and G-CSF. The released factors differed both in type and amount from those released by macrophages treated with the same viral protein. Moreover, Nef treatment slightly reduces the production of small EVs, and the protein was found associated with the small (size < 200 nm) but not the medium/large vesicles (size > 200 nm) collected from GEN2.2 cells. These results add new information on the interactions between this virulence factor and uninfected pDCs, and may provide the basis for further studies on the interactions of Nef protein with primary pDCs.

scholarly journals Achieving dendritic cell subset-specific targeting in vivo by site-directed conjugation of targeting antibodies to nanocarriers

Nano Today ◽  
2022 ◽  
Vol 43 ◽  
pp. 101375
Author(s):  
Johanna Simon ◽  
Michael Fichter ◽  
Gabor Kuhn ◽  
Maximilian Brückner ◽  
Cinja Kappel ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cell Subset ◽  
Dendritic Cell Subset ◽  
Specific Targeting

scholarly journals Absence of CD47 in vivo influences thymic dendritic cell subset proportions but not negative selection of thymocytes

2009 ◽  
Vol 21 (2) ◽  
pp. 167-177 ◽  
Author(s):  
F. Guimont-Desrochers ◽  
C. Beauchamp ◽  
G. Chabot-Roy ◽  
V. Dugas ◽  
E. E. Hillhouse ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Negative Selection ◽  
Cell Subset ◽  
Dendritic Cell Subset ◽  
Thymic Dendritic Cell ◽  
Selection Of

scholarly journals Interferon α/β and Interleukin 12 Responses to Viral Infections

2002 ◽  
Vol 195 (4) ◽  
pp. 517-528 ◽  
Author(s):  
Marc Dalod ◽  
Thais P. Salazar-Mather ◽  
Lene Malmgaard ◽  
Casey Lewis ◽  
Carine Asselin-Paturel ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Lymphocytic Choriomeningitis ◽  
Murine Cytomegalovirus ◽  
Interleukin 12 ◽  
Interferon Α ◽  
Type I ◽  
Type I Ifns ◽  
Immunocompetent Mice

Interferon (IFN)-α/β and interleukin (IL)-12 are cytokines critical in defense against viruses, but their cellular sources and mechanisms of regulation for in vivo expression remain poorly characterized. The studies presented here identified a novel subset of dendritic cells (DCs) as major producers of the cytokines during murine cytomegalovirus (MCMV) but not lymphocytic choriomeningitis virus (LCMV) infections. These DCs differed from those activated by Toxoplasma antigen but were related to plasmacytoid cells, as assessed by their CD8α+Ly6G/C+CD11b− phenotype. Another DC subset (CD8α2Ly6G/C−CD11b+) also contributed to IL-12 production in MCMV-infected immunocompetent mice, modestly. However, it dramatically increased IL-12 expression in the absence of IFN-α/β functions. Conversely, IFN-α/β production was greatly reduced under these conditions. Thus, a cross-regulation of DC subset cytokine responses was defined, whereby secretion of type I IFNs by CD8α+ DCs resulted in responses limiting IL-12 expression by CD11b+ DCs but enhancing overall IFN-α/β production. Taken together, these data indicate that CD8α+Ly6G/C+CD11b− DCs play important roles in limiting viral replication and regulating immune responses, through cytokine production, in some but not all viral infections. They also illustrate the plasticity of cellular sources for innate cytokines in vivo and provide new insights into the roles of IFNs in shaping immune responses to viruses.

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 The BXH2 mutation in IRF8 differentially impairs dendritic cell subset development in the mouse

Blood ◽  
2008 ◽  
Vol 111 (4) ◽  
pp. 1942-1945 ◽  
Author(s):  
Prafullakumar Tailor ◽  
Tomohiko Tamura ◽  
Herbert C. Morse ◽  
Keiko Ozato
Keyword(s):  
Dendritic Cell ◽  
Chromatin Immunoprecipitation ◽  
Cell Subset ◽  
Type I Interferons ◽  
Type I ◽  
Dendritic Cell Subset ◽  
Regulatory Factor ◽  
Mobility Shift ◽  
Type I Ifns ◽  
Plasmacytoid Dcs

Among dendritic cell (DC) subsets, CD8α+ DCs and plasmacytoid DCs (pDCs) produce high levels of IL12 and type I interferons (IFNs), respectively, and confer early innate immunity. Development of CD8α+ DCs and pDCs requires the interferon regulatory factor 8 (IRF8). Recently, a spontaneous point mutation was identified in the Irf8/Icsbp gene in the BXH2 mouse, which exhibits an immunodeficient phenotype similar to the IRF8 knockout (KO) mouse. We show that this mutation, designated IRF8R294C, abolishes the development of CD8α+ DCs without impairing pDC development, and eliminates production of IL12p40, while retaining that of type I IFNs. Electrophoretic mobility shift and chromatin immunoprecipitation assays indicated that IRF8R294C failed to interact with partner transcription factors and did not bind certain promoters that require partner interactions. Together, this work indicates that IRF8-partner interactions play different roles in CD8α+ DCs and pDCs, revealing a mechanistic separation that underlies development of these DC subsets.

scholarly journals SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4

2020 ◽  
Author(s):  
Fanny Onodi ◽  
Lucie Bonnet-Madin ◽  
Laurent Meertens ◽  
Léa Karpf ◽  
Justine Poirot ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Dendritic Cell ◽  
Late Stage ◽  
Antiviral Immunity ◽  
Interferon Α ◽  
Type I ◽  
Type I Ifn ◽  
Ox40 Ligand ◽  
Immune Pathways

Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their interaction with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.

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