Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA394517 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Dendritic cells are the initiators of the adaptive immune response, therefore its gene expression allow us to predict the responses to vaccination. We used bone marrow derived dendritic cells (BMDC) to analyze the gene expression that result from the exposure to adjuvants. We use model antigen OVA and cyclic di-AMP (CDA) as an adjuvant in order to characterize the genes involved in the activation of dendritic cells by CDA alone or when the antigen is present. Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and cellular immunity. The strong STING-dependent stimulation of type I IFN represents a key feature of CDA. However, recent studies suggested that this is dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-γ-secreting CD8+ cytotoxic T lymphocytes (CTL) is significantly decreased after vaccination in the absence of type I IFN signaling. The biological significance of this CTL response was confirmed by the stimulation of MHC class I-restricted protection against influenza virus challenge. We show here that type I IFN (and not TNF-α) is essential for CDA-mediated cross-presentation by a cathepsin independent, TAP and proteosome dependent cytosolic antigen processing pathway, which promotes effective cross-priming and further CTL induction. Our data clearly demonstrate that type I IFN signaling is critical for CDN-mediated cross-presentation
2017-07-15 | GSE101466 | GEO
Project description:The magnitude of CD8+ T lymphocyte (CTL) responses to infection is a function of the available naïve T cell repertoire, combined with the context and duration of antigen presentation. Whilst T cell repertoires are relatively easily studied, the context and abundance of epitopes presented on infected cells and dendritic cells (DCs) and their subsequent impact on CTL responses are generally poorly understood. Using quantitative mass spectrometry, we identified and quantified the abundance of 21 class 1 Major Histocompatibility Complex molecule (MHCI)-restricted influenza A virus (IAV)-derived peptides following either direct presentation or cross-presentation. All identified peptides, including seven novel epitopes, elicited T cell responses in infected C57BL/6 mice. Quantitation of IAV epitopes displayed via direct presentation showed a maintenance of relative epitope abundance across distinct cell types, reflecting common antigen processing mechanisms. Comparison of epitope levels displayed via direct presentation and cross-presentation revealed a broad range of directly presented epitope abundances, which was normalised during cross-presentation. Further, we observed a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drove optimal nucleoprotein (NP)366-374 presentation, while cross-presentation was optimal for acid polymerase (PA)224-233 presentation. This study provides a detailed dissection of viral pMHCI abundance after infection and reveals the importance of both direct and cross-presentation in driving dominant CTL responses. The study also demonstrates how empirical assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.
2019-07-02 | PXD012776 | Pride
Project description:The magnitude of CD8+ T lymphocyte (CTL) responses to infection is a function of the available naïve T cell repertoire, combined with the context and duration of antigen presentation. Whilst T cell repertoires are relatively easily studied, the context and abundance of epitopes presented on infected cells and dendritic cells (DCs) and their subsequent impact on CTL responses are generally poorly understood. Using quantitative mass spectrometry, we identified and quantified the abundance of 21 class 1 Major Histocompatibility Complex molecule (MHCI)-restricted influenza A virus (IAV)-derived peptides following either direct presentation or cross-presentation. All identified peptides, including seven novel epitopes, elicited T cell responses in infected C57BL/6 mice. Quantitation of IAV epitopes displayed via direct presentation showed a maintenance of relative epitope abundance across distinct cell types, reflecting common antigen processing mechanisms. Comparison of epitope levels displayed via direct presentation and cross-presentation revealed a broad range of directly presented epitope abundances, which was normalised during cross-presentation. Further, we observed a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drove optimal nucleoprotein (NP)366-374 presentation, while cross-presentation was optimal for acid polymerase (PA)224-233 presentation. This study provides a detailed dissection of viral pMHCI abundance after infection and reveals the importance of both direct and cross-presentation in driving dominant CTL responses. The study also demonstrates how empirical assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.
2019-07-02 | PXD012728 | Pride
Project description:The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics.The cyclic dinucleotide cyclic-di-guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. Here we provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by cyclic-di- GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, NF-!B and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid-sensing pathways.Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand. Three-condition experiment: macrophages transfected with mono-GMP (negative control), double-stranded DNA (positive control), or cyclic-di-GMP (experimental condition). Biological replicates: two, independently treated, harvested, and hybridized to arrays. One replicate per array, except two technical replicates were performed for one of the positive control samples.
2009-07-21 | E-GEOD-16943 | biostudies-arrayexpress
Project description:The innate immune system responds to unique molecular signatures that are widely conserved among microbes but that are not normally present in host cells. Compounds that stimulate innate immune pathways may be valuable in the design of novel adjuvants, vaccines, and other immunotherapeutics.The cyclic dinucleotide cyclic-di-guanosine monophosphate (c-di-GMP) is a recently appreciated second messenger that plays critical regulatory roles in many species of bacteria but is not produced by eukaryotic cells. In vivo and in vitro studies have previously suggested that c-di-GMP is a potent immunostimulatory compound recognized by mouse and human cells. Here we provide evidence that c-di-GMP is sensed in the cytosol of mammalian cells via a novel immunosurveillance pathway. The potency of cytosolic signaling induced by cyclic-di- GMP is comparable to that induced by cytosolic delivery of DNA, and both nucleic acids induce a similar transcriptional profile, including triggering of type I interferons and coregulated genes via induction of TBK1, IRF3, NF-!B and MAP kinases. However, the cytosolic pathway that senses c-di-GMP appears to be distinct from all known nucleic acid-sensing pathways.Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand.
2009-07-22 | GSE16943 | GEO
Project description:Nucleotide signaling pathways are found in all kingdoms of life and are utilized to coordinate a rapid response to changes in the environment. One more recently discovered signaling nucleotide is the secondary messenger cyclic diadenosine monophosphate (c-di-AMP), which is widely distributed among bacteria and is also found in several archaea. This cyclic nucleotide has been shown to involve in several important cellular processes, including maintenance of DNA integrity, cell wall metabolism, stress tolerance, transcription regulation and virulence. However, the mechanisms by which c-di-AMP modulates these physiological changes have remained largely unknown.In the present study, we identified and characterized a c-di-AMP synthase (CdaA) in S. mutans UA159. Furthermore, we investigated the role of CdaA in S. mutans cell physiology and global gene expression by utilizing cdaA gene in-frame deletion mutant. Our findings suggest that CdaA is an important global modulator of optimal growth and environmental adaption in this pathogen.
2015-04-06 | GSE65511 | GEO
Project description:This a model from the article:
A dynamical perspective of CTL cross-priming and regulation: implications for
cancer immunology.
Wodarz D, Jansen VA. Immunol Lett
2003 May 1;86(3):213-27 12706524
,
Abstract:
Cytotoxic T lymphocytes (CTL) responses are required to fight many diseases such
as viral infections and tumors. At the same time, they can cause disease when
induced inappropriately. Which factors regulate CTL and decide whether they
should remain silent or react is open to debate. The phenomenon called
cross-priming has received attention in this respect. That is, CTL expansion
occurs if antigen is recognized on the surface of professional antigen
presenting cells (APCs). This is in contrast to direct presentation where
antigen is seen on the surface of the target cells (e.g. infected cells or tumor
cells). Here we introduce a mathematical model, which takes the phenomenon of
cross-priming into account. We propose a new mechanism of regulation which is
implicit in the dynamics of the CTL: According to the model, the ability of a
CTL response to become established depends on the ratio of cross-presentation to
direct presentation of the antigen. If this ratio is relatively high, CTL
responses are likely to become established. If this ratio is relatively low,
tolerance is the likely outcome. The behavior of the model includes a parameter
region where the outcome depends on the initial conditions. We discuss our
results with respect to the idea of self/non-self discrimination and the danger
signal hypothesis. We apply the model to study the role of CTL in cancer
initiation, cancer evolution/progression, and therapeutic vaccination against
cancers.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Wodarz D, Jansen VA. (2003) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000685 | BioModels
Project description:Nucleotide signaling pathways are found in all kingdoms of life and are utilized to coordinate a rapid response to changes in the environment. One more recently discovered signaling nucleotide is the secondary messenger cyclic diadenosine monophosphate (c-di-AMP), which is widely distributed among bacteria and is also found in several archaea. This cyclic nucleotide has been shown to involve in several important cellular processes, including maintenance of DNA integrity, cell wall metabolism, stress tolerance, transcription regulation and virulence. However, the mechanisms by which c-di-AMP modulates these physiological changes have remained largely unknown.In the present study, we identified and characterized a c-di-AMP synthase (CdaA) in S. mutans UA159. Furthermore, we investigated the role of CdaA in S. mutans cell physiology and global gene expression by utilizing cdaA gene in-frame deletion mutant. Our findings suggest that CdaA is an important global modulator of optimal growth and environmental adaption in this pathogen. Streptococcus mutans UA159 whole-genome arrays (8 x 15 K) were obtained from Agilent and included 1998 probes for S. mutans transcripts. For microarray analysis, S. mutans UA159 and S. mutans ?cdaA cells were routinely grown at 37°C anaerobically (90% N2, 5% CO2, 5% H2) in brain heart infusion broth (BHI; Difco, Sparks, MD, USA) to an optical density at 600 nm (OD600) of 0.5. Four RNA samples isolated from four independent cultures of UA159 and cdaA mutant strains were hybridized to the arrays and analyzed.
2015-04-06 | E-GEOD-65511 | biostudies-arrayexpress
Project description:The ability of dying cells to activate antigen presenting cells (APCs) is carefully controlled to avoid unwarranted inflammatory responses. Here we show that engulfed cells only containing cytosolic dsDNA species (viral or synthetic) or cyclic di-nucleotides (CDNs) are able to stimulate APCs, via extrinsic STING-signaling. HEK293 cells containing double strand DNA robustly induced the production of cytokines in macrophages that was dependent on extrinsic STING signaling within the macrophage.
2018-09-04 | GSE110929 | GEO