The Modular Nature of Dendritic Cell Responses to Commensal and Pathogenic Fungi
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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/315244", "https://ndownloader.figshare.com/files/315294", "https://ndownloader.figshare.com/files/315365", "https://ndownloader.figshare.com/files/315422", "https://ndownloader.figshare.com/files/315478", "https://ndownloader.figshare.com/files/315511", "https://ndownloader.figshare.com/files/315624", "https://ndownloader.figshare.com/files/315702", "https://ndownloader.figshare.com/files/315761", "https://ndownloader.figshare.com/files/315840", "https://ndownloader.figshare.com/files/315905", "https://ndownloader.figshare.com/files/315983", "https://ndownloader.figshare.com/files/316032", "https://ndownloader.figshare.com/files/316076", "https://ndownloader.figshare.com/files/316111"], "description"=>"<div><p>The type of adaptive immune response following host-fungi interaction is largely determined at the level of the antigen-presenting cells, and in particular by dendritic cells (DCs). The extent to which transcriptional regulatory events determine the decision making process in DCs is still an open question. By applying the highly structured DC-ATLAS pathways to analyze DC responses, we classified the various stimuli by revealing the modular nature of the different transcriptional programs governing the recognition of either pathogenic or commensal fungi. Through comparison of the network parts affected by DC stimulation with fungal cells and purified single agonists, we could determine the contribution of each receptor during the recognition process. We observed that initial recognition of a fungus creates a temporal window during which the simultaneous recruitment of cell surface receptors can intensify, complement and sustain the DC activation process. The breakdown of the response to whole live cells, through the purified components, showed how the response to invading fungi uses a set of specific modules. We find that at the start of fungal recognition, DCs rapidly initiate the activation process. Ligand recognition is further enhanced by over-expression of the receptor genes, with a significant correspondence between gene expression and protein levels and function. Then a marked decrease in the receptor levels follows, suggesting that at this moment the DC commits to a specific fate. Overall our pathway based studies show that the temporal window of the fungal recognition process depends on the availability of ligands and is different for pathogens and commensals. Modular analysis of receptor and signalling-adaptor expression changes, in the early phase of pathogen recognition, is a valuable tool for rapid and efficient dissection of the pathogen derived components that determine the phenotype of the DC and thereby the type of immune response initiated.</p> </div>", "links"=>[], "tags"=>["modular", "dendritic", "responses", "commensal", "pathogenic", "fungi"], "article_id"=>122208, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0042430.s001", "https://dx.doi.org/10.1371/journal.pone.0042430.s002", "https://dx.doi.org/10.1371/journal.pone.0042430.s003", "https://dx.doi.org/10.1371/journal.pone.0042430.s004", "https://dx.doi.org/10.1371/journal.pone.0042430.s005", "https://dx.doi.org/10.1371/journal.pone.0042430.s006", "https://dx.doi.org/10.1371/journal.pone.0042430.s007", "https://dx.doi.org/10.1371/journal.pone.0042430.s008", "https://dx.doi.org/10.1371/journal.pone.0042430.s009", "https://dx.doi.org/10.1371/journal.pone.0042430.s010", "https://dx.doi.org/10.1371/journal.pone.0042430.s011", "https://dx.doi.org/10.1371/journal.pone.0042430.s012", "https://dx.doi.org/10.1371/journal.pone.0042430.s013", "https://dx.doi.org/10.1371/journal.pone.0042430.s014", "https://dx.doi.org/10.1371/journal.pone.0042430.s015"], "stats"=>{"downloads"=>6, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Modular_Nature_of_Dendritic_Cell_Responses_to_Commensal_and_Pathogenic_Fungi/122208", "title"=>"The Modular Nature of Dendritic Cell Responses to Commensal and Pathogenic Fungi", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-08-03 00:36:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/596415"], "description"=>"<p>Following DC-ATLAS pathway structure, receptor/sensing modules, transduction modules and the outcome modules were represented for (A) Dectin-1 signaling and (B) DC-SIGN signaling. For the outcome modules the cytokines measured within the manuscript are indicated (bold). These graphs present both the vertical and horizontal resolution of DC-TLAS pathways. For the complete BCML pathways, please see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042430#pone.0042430.s001\" target=\"_blank\">Figure S1</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042430#pone.0042430.s002\" target=\"_blank\">S2</a>. Note: the TLP1-mediated signalosome upon DC-SIGN engagement recently described has not been drawn to simplify view of the modules.</p>", "links"=>[], "tags"=>["dc-sign", "dectin-1"], "article_id"=>266910, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042430.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Flowchart_of_DC_SIGN_and_Dectin_1_signalling_/266910", "title"=>"Flowchart of DC-SIGN and Dectin-1 signalling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-03 01:55:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/596545"], "description"=>"<p>Clustering of pathway Enrichment Factor (PEFs) obtained from the FET analysis on DC samples challenged with fungi. (A) Pathway signatures generated on DC-ATLAS. (B) Insert of the pathway signature generated using immune-related public pathway available from KEGG and Reactome. The detail highlights the available pathway involved in the initial recognition of an antigen, in particular the TLR signalings. The complete clustering is available as <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042430#pone.0042430.s003\" target=\"_blank\">Figure S3</a>. Colored spots indicate significant (p≤0.05) up- (red) or down- (green) regulation. The colors of the dendrogram indicate the percentages of the tree support (significance), from 50% (pink) to 100% (black).</p>", "links"=>[], "tags"=>["signaling", "fungal", "receptor"], "article_id"=>267035, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042430.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DC_driven_signaling_response_upon_fungal_receptor_engagement_/267035", "title"=>"DC-driven signaling response upon fungal receptor engagement.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-03 01:57:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/597075"], "description"=>"<p>Transcriptional analysis was performed on DCs after 4 hours of stimulation with Curdlan, Zymosan, Mannan and <i>S. cerevisiae</i> yeast or without any stimuli. (A) Venn diagram of upregulated DEGs. (B) IR differentially regulated genes (p≤0.05) commonly expressed among the four stimulation conditions. (C) IR differentially regulated genes (p≤0.05) commonly expressed among Zymosan and <i>S. cerevisiae</i> yeast stimulation condition and not affected upon single cell wall components stimulation. (D) Cytokine detection assays were performed for IL-1β, TNFα, IL-6 and IL-12p70 measurement on supernatants of DCs stimulated for 18 hours with Sc cells or zymosan; **p<0.01.</p>", "links"=>[], "tags"=>["genes", "activated", "components"], "article_id"=>267564, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042430.g007", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immune_response_IR_genes_activated_by_different_cell_wall_components_and_Saccharomyces_cerevisiae_in_DCs_/267564", "title"=>"Immune response (IR) genes activated by different cell wall components and <i>Saccharomyces cerevisiae</i> in DCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-03 02:06:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/596846"], "description"=>"<p>(A) Clustering selection of Pathway Enrichment Factor (PEFs) obtained from the FET analysis on DC samples stimulated with Curdlan in time. Colored spots indicate significant (p, 0.05) up- (red) or down- (green) regulation. The colors of the dendrogram indicate the percentages of the tree support (significance), from 50% (pink) to 100% (black). (B) <i>CLEC7A, SYK, RAF1</i> and <i>CARD9</i> gene expression on DCs upon Curdlan stimulation. Gene expression was assessed by RT- PCR on DCs stimulated with Curdlan for 5, 15, 30, 60 and 120 minutes. (mean ± SD, N = 3). (C) DC modulation of gene expression of CLR or TLR signalling. The specificity of signals to different PRR agonists was assessed by real-time PCR on DCs stimulated with Curdlan or LPS for 5, 15, 30, 60, 120 and 240 minutes (mean ± SD, N = 3). (D) The differences at the sensing level, between <i>C. albicans</i> hyphae and Sc cells stimulation were addressed by RT-PCR. <i>CLEC7A</i> and <i>SYK</i> gene expression on DCs upon challenge with <i>C. albicans</i> hyphae and <i>S. cerevisiae</i> cells was assessed on DCs stimulated for 1, 2, 4, 8 and 12 hours (mean ±SD, N = 3): **p<0.01, ***p<0.001. (E) <i>CARD9</i> gene expression on DCs upon challenge with Sc cells. Gene expression was assessed in RT-PCR on DCs stimulated over time (mean ± SD, N = 3); FC, fold change was calculated by comparing the stimulated condition at various time points with the unstimulated control after normalization to the expression of the houskeeping gene GAPDH.</p>", "links"=>[], "tags"=>["modular", "structures", "ligand", "differences", "fungi"], "article_id"=>267335, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042430.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dectin_1_modular_structures_in_response_to_ligand_concentration_determine_differences_in_fungi_recognition_/267335", "title"=>"Dectin-1 modular structures in response to ligand concentration determine differences in fungi recognition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-03 02:02:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/597188"], "description"=>"<p>The microarray datasets used in the manuscript are directly accessible from <a href=\"http://dc-atlas.net/datasets/and\" target=\"_blank\">http://dc-atlas.net/datasets/and</a> Array Express (<a href=\"http://www.ebi.ac.uk/arrayexpress/experiments\" target=\"_blank\">www.ebi.ac.uk/arrayexpress/experiments</a>).</p>", "links"=>[], "tags"=>["experiments", "dcs", "challenged", "fungi"], "article_id"=>267678, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042430.t001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Microarray_experiments_on_DCs_challenged_with_fungi_and_single_agonists_/267678", "title"=>"Microarray experiments on DCs challenged with fungi and single agonists.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-08-03 02:07:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/596707"], "description"=>"<p>Cytokines profiles confirm the differences in immune recognition. (A) Cytokines production upon CLR and TLR agonist engagement. DCs were stimulated with Curdlan, LPS or without any stimuli for 18 hours. The level of IL-1β, TNFα, IL-12p70 and IL-6 production was measured using the Milliplex® technology. (B) Cytokine level detection on DC supernatants upon stimulation with the live <i>Candida</i> or Sc cells for 18 hours. Detection was performed as mentioned above. **p<0.01, ***p<0.001.</p>", "links"=>[], "tags"=>["highlighted", "pathway", "revealed", "cytokine"], "article_id"=>267197, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042430.g004", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Differences_highlighted_in_pathway_analysis_are_revealed_in_cytokine_induction_/267197", "title"=>"Differences highlighted in pathway analysis are revealed in cytokine induction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-03 01:59:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/596928"], "description"=>"<p>DCs were stimulated with live <i>S. cerevisiae</i> (Sc) cells, <i>Candida</i> (A) or different concentration of Curdlan (µg/ml, B, C) for the time indicated. Cell lysates were isolated and immunoblotted with the specific primary antibodies and reprobed with anti-β-tubulin antibody to control for the equal loading of cell lysates. Representative blots are shown. Quantitative analysis of protein expression is summarized in bar graphs, presented as mean integrated intensity of specific bands normalized to β-tubulin ± SD of 3–5 independent experiments.</p>", "links"=>[], "tags"=>["analyses", "dectin-1", "syk", "fungal"], "article_id"=>267420, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042430.g006", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunoblot_analyses_of_Dectin_1_and_Syk_upon_fungal_recognition_/267420", "title"=>"Immunoblot analyses of Dectin-1 and Syk upon fungal recognition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-03 02:03:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/596639"], "description"=>"<p>Transcriptional analysis was performed on DCs after 4 hours of stimulation with Curdlan, Zymosan, Mannan, Sc cells and spores or without any stimuli. Clustering of Pathway Enrichment Factors (PEFs) were obtained from the FET analysis of challenged DC samples and compared with those obtained on DC stimulated with whole fungi or the publicly available dataset of LPS or R848 stimulated DCs. Colored spots indicate significant (p≤0.05) up- (red) or down- (green) regulation. The colors of the dendrogram indicate the percentages of the tree support (significance), from 50% (pink) to 100% (black).</p>", "links"=>[], "tags"=>["signaling", "c-lectin", "tlr"], "article_id"=>267128, "categories"=>["Biological Sciences", "Genetics", "Microbiology", "Immunology"], "users"=>["Lisa Rizzetto", "Sonja I. Buschow", "Luca Beltrame", "Carl G. Figdor", "Stephan Schierer", "Gerold Schuler", "Duccio Cavalieri"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0042430.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DC_driven_signaling_response_upon_fungi_C_lectin_and_TLR_agonists_/267128", "title"=>"DC-driven signaling response upon fungi, C-lectin and TLR agonists.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-08-03 01:58:48"}

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