Nonspreading Rift Valley Fever Virus Infection of Human Dendritic Cells Results in Downregulation of CD83 and Full Maturation of Bystander Cells
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Mendeley | Further Information

{"title"=>"Nonspreading Rift Valley Fever Virus Infection of Human Dendritic Cells Results in Downregulation of CD83 and Full Maturation of Bystander Cells.", "type"=>"journal", "authors"=>[{"first_name"=>"Nadia", "last_name"=>"Oreshkova"}, {"first_name"=>"Paul J", "last_name"=>"Wichgers Schreur"}, {"first_name"=>"Lotte", "last_name"=>"Spel"}, {"first_name"=>"Rianka P M", "last_name"=>"Vloet"}, {"first_name"=>"Rob J M", "last_name"=>"Moormann"}, {"first_name"=>"Marianne", "last_name"=>"Boes"}, {"first_name"=>"Jeroen", "last_name"=>"Kortekaas"}], "year"=>2015, "source"=>"PloS one", "identifiers"=>{"issn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0142670", "pmid"=>"26575844"}, "keywords"=>["Antigens, CD", "Antigens, CD80", "Antigens, CD80: genetics", "Antigens, CD80: metabolism", "Antigens, CD: genetics", "Antigens, CD: metabolism", "Cell Differentiation", "Cells, Cultured", "Cytokines", "Cytokines: secretion", "Dendritic Cells", "Dendritic Cells: immunology", "Dendritic Cells: metabolism", "Dendritic Cells: virology", "Down-Regulation", "Gene Expression", "Glyceraldehyde-3-Phosphate Dehydrogenases", "Glyceraldehyde-3-Phosphate Dehydrogenases: genetic", "Glyceraldehyde-3-Phosphate Dehydrogenases: metabol", "Host-Pathogen Interactions", "Humans", "Immunoglobulins", "Immunoglobulins: genetics", "Immunoglobulins: metabolism", "Lipopolysaccharides", "Lipopolysaccharides: pharmacology", "Membrane Glycoproteins", "Membrane Glycoproteins: genetics", "Membrane Glycoproteins: metabolism", "Proteasome Endopeptidase Complex", "Proteasome Endopeptidase Complex: metabolism", "Proteolysis", "Rift Valley Fever", "Rift Valley Fever: immunology", "Rift Valley Fever: prevention & control", "Rift Valley Fever: virology", "Rift Valley fever virus", "Rift Valley fever virus: immunology", "Vaccines, Attenuated", "Vaccines, Attenuated: immunology", "Viral Vaccines", "Viral Vaccines: immunology", "Virus Replication"], "id"=>"0875118d-fc17-3d63-8d19-94fe4c1d4028", "abstract"=>"Vaccines based on nonspreading Rift Valley fever virus (NSR) induce strong humoral and robust cellular immune responses with pronounced Th1 polarisation. The present work was aimed to gain insight into the molecular basis of NSR-mediated immunity. Recent studies have demonstrated that wild-type Rift Valley fever virus efficiently targets and replicates in dendritic cells (DCs). We found that NSR infection of cultured human DCs results in maturation of DCs, characterized by surface upregulation of CD40, CD80, CD86, MHC-I and MHC-II and secretion of the proinflammatory cytokines IFN-β, IL-6 and TNF. Interestingly, expression of the most prominent marker of DC maturation, CD83, was consistently downregulated at 24 hours post infection. Remarkably, NSR infection also completely abrogated CD83 upregulation by LPS. Downregulation of CD83 was not associated with reduced mRNA levels or impaired CD83 mRNA transport from the nucleus and could not be prevented by inhibition of the proteasome or endocytic degradation pathways, suggesting that suppression occurs at the translational level. In contrast to infected cells, bystander DCs displayed full maturation as evidenced by upregulation of CD83. Our results indicate that bystander DCs play an important role in NSR-mediated immunity.", "link"=>"http://www.mendeley.com/research/nonspreading-rift-valley-fever-virus-infection-human-dendritic-cells-results-downregulation-cd83-ful", "reader_count"=>4, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>1, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>2, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2444254"], "description"=>"<p>(A) DCs were infected with NSR for 24 h and evaluated for expression of GFP, using an EVOS fluorescence microscope. (B) Infection efficiency under optimal conditions as determined by flow cytometry. (C) Viability and percentage of infected cells at different time points after infection. Cells were infected with NSR or mock-infected with NSRmock, harvested at the indicated time points, stained with 7AAD and analysed by flow cytometry. The percentage of GFP expressing cells (bars) and the viability after NSR or NSRmock infections (lines) is depicted. Viability of the cells was calculated relative to the viability at 8 hpi, which was set at 100%. The data depict average values from two experiments with cells from two different donors ±SD. (D) Morphology of DCs stimulated with the indicated stimuli at 24 h post treatment.</p>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605831, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142670.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Infection_of_DCs_by_NSR_/1605831", "title"=>"Infection of DCs by NSR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-17 15:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2444255"], "description"=>"<p>Supernatants of infected or control-treated DCs were harvested at 24 hpi and analysed with a luminex-based cytokine assay. Bars represent the mean cytokine concentrations ± SD of triplicates with cells from one donor. Statistical significance between infected (NSR) and mock-infected (NSRmock) conditions is indicated.</p>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605832, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142670.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cytokine_secretion_by_NSR_infected_DCs_/1605832", "title"=>"Cytokine secretion by NSR-infected DCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-17 15:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2444256"], "description"=>"<p>Immature DCs were infected with NSR, mock-infected with NSRmock, or stimulated with LPS (left and middle panels). Alternatively, cells were infected with NSR or mock-infected with NSRmock in the presence of LPS (right panels). The left panel shows representative histograms of surface marker measurements on cells stimulated with LPS, mock infected cells (NSRmock), cells infected with NSR (GFP+) and uninfected bystander DCs (GFP-). Expression of markers in untreated cells and an irrelevant isotype control are depicted. The middle and right panels represent average data from 4 independent experiments performed with cells from 3 donors. The box plots depict MFI of the different markers relative to untreated cells. A black asterisk indicates upregulation compared to the control and a red asterisk indicates downregulation.</p>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605833, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142670.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Surface_expression_of_CD40_CD80_CD83_CD86_MHC_I_and_MHC_II_on_DCs_at_24_h_after_NSR_infection_as_measured_by_flow_cytometry_/1605833", "title"=>"Surface expression of CD40, CD80, CD83, CD86, MHC-I and MHC-II on DCs at 24 h after NSR infection as measured by flow cytometry.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-17 15:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2444257"], "description"=>"<p>DCs were treated with NSRmock, NSR, LPS, LPS+NSRmock or LPS+NSR and were harvested at 0, 4, 8,12, 16, 24 and 48 h post treatment. Surface expression of CD83 (upper panels) and CD80 (lower panels) were measured by flow cytometry. Left panels show histograms from one representative experiment. Time points are depicted with different colors and the color code is shown at the right. IC–isotype control. Right panels illustrate average data from three independent experiments with cells from three different donors. Bars represent means ±SD of the fold change of MFI relative to untreated cells.</p>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605834, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142670.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_CD83_and_CD80_surface_expression_in_time_/1605834", "title"=>"Analysis of CD83 and CD80 surface expression in time.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-17 15:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2444258"], "description"=>"<p>DC RNA samples, prepared 24 h after treatment (as indicated), were analysed by qRT-PCR. Bars represent average Ct values from triplicates ±SD with cells from one donor. The experiment is a representative of 3 independently performed experiments with cells from 3 different donors. Statistical significance is indicated with an asterisk.</p>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605835, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142670.g005", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_CD83_CD80_GAPDH_and_PPIA_mRNA_levels_/1605835", "title"=>"Analysis of CD83, CD80, GAPDH and PPIA mRNA levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-17 15:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2444259"], "description"=>"<p>DCs were stimulated for 24 h with LPS, infected with NSR or left untreated and then fixed and subjected to FISH. Shown are (A) representative cells of each treatment condition from three independently performed experiments with cells from three different donors and (B) average ±SD spot counts of cells probed for GAPDH, CD80 and CD83. Relevant statistical significance is indicated with an asterisk.</p>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605836, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142670.g006", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Visualization_of_GAPDH_CD80_and_CD83_mRNAs_in_infected_cells_using_FISH_/1605836", "title"=>"Visualization of GAPDH, CD80 and CD83 mRNAs in infected cells using FISH.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-17 15:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2444260"], "description"=>"<p>(A) The levels of soluble CD83 in supernatants from cells harvested 24 h after stimulation with LPS, infection with NSR, or from cells mock infected with NSRmock were determined by ELISA. Bars represent average CD83 concentrations ±SD. Results from one of two independently performed experiments with similar results are shown. (B) Detection of CD83 in cell lysates by Western blot at 24 hpi. The different treatments are shown above the top panel and the probed proteins are depicted at the right. The positions of molecular weight standard proteins are shown at the left. The top blot was stripped and re-probed with antibodies against GAPDH and GFP, which served as loading control and control to confirm NSR infection, respectively. Results from one of two independent experiments with cells from two donors are shown.</p>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605837, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142670.g007", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_NSR_infection_on_intracellular_and_extracellular_CD83_levels_/1605837", "title"=>"Effect of NSR infection on intracellular and extracellular CD83 levels.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-17 15:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2444261"], "description"=>"<p>(A) Flow cytometry analysis of CD83 surface expression after inhibition of the proteasome. DCs were stimulated with NSRmock, LPS+NSRmock or LPS+NSR for 8 h and then clasto Lactacystin β-lactone (CLBL) was added at two concentrations, as indicated. Control cells were left untreated or were treated with DMSO. Cells were analysed at 24 hpi for CD83 expression. Bars represent average MFI ±SD from two experiments with cells from one donor (B) Detection of total amounts of CD83 in cell lysates by Western blot. Cells were stimulated as described under point “A” and treatments are indicated above the image. (C) Inhibition of endocytosis. DCs were stimulated with LPS+NSRmock, LPS+NSR or left unstimulated. Cytochalasin D (Cyt D) or the solvent DMSO were subsequently added at different time points. The moments of adding Cyt D/DMSO and harvesting of cells are indicated above each graph. Bars represent average fold change of the MFI relative to unstimulated cells treated with DMSO ±SD. Average values of three experiments with cells from one donor are depicted. Relevant statistical significances are shown.</p>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605838, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0142670.g008", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_CD83_after_inhibition_of_cellular_protein_degradation_routes_/1605838", "title"=>"Expression of CD83 after inhibition of cellular protein degradation routes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-11-17 15:14:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/2444262", "https://ndownloader.figshare.com/files/2444263", "https://ndownloader.figshare.com/files/2444264"], "description"=>"<div><p>Vaccines based on nonspreading Rift Valley fever virus (NSR) induce strong humoral and robust cellular immune responses with pronounced Th1 polarisation. The present work was aimed to gain insight into the molecular basis of NSR-mediated immunity. Recent studies have demonstrated that wild-type Rift Valley fever virus efficiently targets and replicates in dendritic cells (DCs). We found that NSR infection of cultured human DCs results in maturation of DCs, characterized by surface upregulation of CD40, CD80, CD86, MHC-I and MHC-II and secretion of the proinflammatory cytokines IFN-β, IL-6 and TNF. Interestingly, expression of the most prominent marker of DC maturation, CD83, was consistently downregulated at 24 hours post infection. Remarkably, NSR infection also completely abrogated CD83 upregulation by LPS. Downregulation of CD83 was not associated with reduced mRNA levels or impaired CD83 mRNA transport from the nucleus and could not be prevented by inhibition of the proteasome or endocytic degradation pathways, suggesting that suppression occurs at the translational level. In contrast to infected cells, bystander DCs displayed full maturation as evidenced by upregulation of CD83. Our results indicate that bystander DCs play an important role in NSR-mediated immunity.</p></div>", "links"=>[], "tags"=>["CD 83", "lps", "Th 1 polarisation", "bystander DCs", "Nonspreading Rift Valley Fever Virus Infection", "ifn", "24 hours post infection", "Human Dendritic Cells Results", "nonspreading Rift Valley fever virus", "Bystander Cells Vaccines", "NSR infection", "CD 83 mRNA transport", "endocytic degradation pathways", "tnf", "il", "CD 83 upregulation"], "article_id"=>1605839, "categories"=>["Biological Sciences"], "users"=>["Nadia Oreshkova", "Paul J. Wichgers Schreur", "Lotte Spel", "Rianka P. M. Vloet", "Rob J. M. Moormann", "Marianne Boes", "Jeroen Kortekaas"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0142670.s001", "https://dx.doi.org/10.1371/journal.pone.0142670.s002", "https://dx.doi.org/10.1371/journal.pone.0142670.s003"], "stats"=>{"downloads"=>3, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nonspreading_Rift_Valley_Fever_Virus_Infection_of_Human_Dendritic_Cells_Results_in_Downregulation_of_CD83_and_Full_Maturation_of_Bystander_Cells_/1605839", "title"=>"Nonspreading Rift Valley Fever Virus Infection of Human Dendritic Cells Results in Downregulation of CD83 and Full Maturation of Bystander Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-11-17 15:14:06"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"6", "full-text"=>"4", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2021", "month"=>"1"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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