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Analysis of early dendritic cell, natural killer cell and B lymphocyte responses to murine cytomegalovirus (MCMV) infection by genome-wide expression profiling

ABSTRACT: Dendritic cells (DCs) are a complex group of cells which play a critical role in vertebrate immunity. They are subdivided into conventional DC (cDC) subsets (CD11b and CD8alpha in mouse) and plasmacytoid DCs (pDCs). Natural killer cells are innate lymphocytes involved in the recognition and killing of abnormal self cells, including virally infected cells or tumor cells. DCs and NK cells are activated very early upon viral infections and regulate one another. However, the global responses of DC and NK cells early after viral infection in vivo and their molecular regulation are not entirely characterized. The goal of this experiment was to use global gene expression profiling to assess the global genetic reprogramming of DC and NK cells during a viral infection in vivo, as compared to B lymphocytes, and to investigate the underlying molecular mechanisms This study includes data from cell sort purified DCs, NK cells and B cells isolated from the spleen of MCMV-infected mice. 2 independent replicates were made for each cell type except B cells. The control dataset for cells isolated from uninfected control animals has been previously published and is available in the GEO database as GSE9810. The complete dataset representing: (1) the infected Samples and (2) the uninfected control Samples from Series GSE9810 (re-processed using RMA), is linked below as a supplementary file.

ORGANISM(S): Mus musculus

PROVIDER: GSE21491 | GEO | 2012/10/17

SECONDARY ACCESSION(S): PRJNA126031

REPOSITORIES: GEO

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Analysis of early dendritic cell, natural killer cell and B lymphocyte responses to murine cytomegalovirus (MCMV) infection by genome-wide expression profiling

Project description:Dendritic cells (DCs) are a complex group of cells which play a critical role in vertebrate immunity. They are subdivided into conventional DC (cDC) subsets (CD11b and CD8alpha in mouse) and plasmacytoid DCs (pDCs). Natural killer cells are innate lymphocytes involved in the recognition and killing of abnormal self cells, including virally infected cells or tumor cells. DCs and NK cells are activated very early upon viral infections and regulate one another. However, the global responses of DC and NK cells early after viral infection in vivo and their molecular regulation are not entirely characterized. The goal of this experiment was to use global gene expression profiling to assess the global genetic reprogramming of DC and NK cells during a viral infection in vivo, as compared to B lymphocytes, and to investigate the underlying molecular mechanisms This study includes data from cell sort purified DCs, NK cells and B cells isolated from the spleen of MCMV-infected mice. 2 independent replicates were made for each cell type except B cells. The control dataset for cells isolated from uninfected control animals has been previously published and is available in the GEO database as GSE9810. The complete dataset representing: (1) the infected Samples and (2) the uninfected control Samples from Series GSE9810 (re-processed using RMA), is linked below as a supplementary file. Comparison of the gene expression programs of wild-type spleen leukocyte subsets, including plasmacytoid DCs, CD8alpha conventional DCs, CD11b conventional DCs and NK cells, isolated from MCMV-infected versus control animals.

2012-10-17 | E-GEOD-21491 | biostudies-arrayexpress

Genome-wide expression study of the responses of murine NK cells and dendritic cell subsets to MCMV infection

Project description:Murine Cytomegalovirus (MCMV) infection leads to the activation of various immune cells, including dendritic cells (DCs) and Natural Killer (NK) cells. This activation is partly driven by innate cytokines including IFN-I, which are induced early after infection. The objective was to address the role of different innate cytokines in shaping DC subsets and NK cell responses, in particular the role of cell intrinsic responses to IFN-I. In order to decipher the specific impact of cell-intrinsic IFN-I on cell subsets, we performed a genome-wide expression analysis on CD45.1 WT and CD45.2 IFNAR-/- splenic conventional DC (cDC) subsets and NK cells isolated from C57BL/6 [CD45.1 WT / CD45.2 IFNAR-KO] mixed bone marow chimera mice. This study includes data from cDC subsets (CD8a and CD11b) and NK cells purified by flow cytometry sorting from the spleen of bone marrow chimera (BMC) mice, under steady-state or MCMV condition. Two independent replicates were made for each cell type, from two independent pools of spleens from uninfected or d1.5 MCMV-infected BMC 5-8 mice, and were hybridized on 3 separate batches of gene chips.

2012-10-17 | E-GEOD-39555 | biostudies-arrayexpress

CCL4 Secretion By Interleukin-15 Dendritic Cells Directs Superior Recruitment Of Cd56+ Cytolytic Lymphocytes

Project description:A key requisite for the success of a dendritic cell (DC)-based vaccine in treating malignancies is the capacity of the DCs to attract immune effector cells for further interaction and activation, considering crosstalk with DCs is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC therapy. In this paper we examine if the so-called interleukin (IL)-15 DC vaccine provides a favorable chemokine milieu for recruiting T cells, natural killer (NK) cells and gamma delta (γδ) T cells, in comparison with the IL-4 DCs used routinely for clinical studies, as well as the underlying mechanisms of immune cell attraction by IL-15 DCs. Chemokine signaling is studied both at the RNA level, using microarray data of mature DCs, and functional level, by means of a transwell chemotaxis assay. Important to note, the classic IL-4 DC vaccine falls short to attract the required immune effector lymphocytes, whereas the IL-15 DCs provide a favorable chemokine milieu for recruiting all cytolytic effector cells. The elevated secretion of the chemokine (C-C motif) ligand 4 (CCL4), also known as macrophage inflammatory protein-1β (MIP-1β), by IL-15 DCs underlies the enhanced migratory responsiveness of T cells, NK cells and γδ T cells. Namely, neutralizing its receptor CCR5 resulted in a significant drop in migration of the aforementioned effector cells towards IL-15 DCs. These findings should be kept in mind in the design of future DC-based cancer vaccines.

2016-03-17 | GSE79184 | GEO

Phosphoproteome analysis of bone marrow-derived dendritic cells infected by Francisella tularensis – proteome dataset

Project description:Francisella tularensis is a highly infective Gram-negative bacterium, also known as the causative agent of tularemia. The disease is characterized by the delayed onset of the adaptive immune response which provides time for the bacterial replication. As an intracellular pathogen, Francisella proliferates mainly in the cytosol of host phagocytes, which are linkers between the innate and the adaptive immunity. In particular, dendritic cells (DCs) are known to be the most effective antigen-presenting cells and thus they are crucial for the induction of the adaptive response. However, Francisella is able to invade and to proliferate inside DCs while avoiding their effective activation and maturation. The uploaded dataset relates to phosphoproteome analysis of DCs infected by virulent and attenuated Francisella strains (dataset identifier PXD005747) and provides data of DC proteome changes at 60 min p.i.

2017-10-26 | PXD006759 | Pride

Transcriptional profiles of human blood dendritic cell (DC) subsets at steady state

Project description:Innate sensing of viruses by dendritic cells (DCs) is critical for the initiation of anti-viral adaptive immune responses. Virus, however, have evolved to suppress immune activation in infected cells. We now analyze the susceptibility of different populations of dendritic cells to viral infections. We find that circulating human CD1c+ DCs support infection by HIV and influenza virus. Viral infection of CD1c+ DCs is essential for virus-specific CD8+ T cell activation and cytosolic sensing of the virus. In contrast, circulating human CD141+ DCs and pDCs constitutively limit viral fusion. The small GTPase RAB15 mediates this differential viral resistance in DC subsets through selective expression in CD141+ DCs and pDCs. Therefore, dendritic cell sub-populations evolved constitutive resistance mechanisms to mitigate viral infection during induction of antiviral immune response.

2017-05-22 | GSE76511 | GEO

Loss of Fas (CD95) expression by dendritic cells protects from a chronic viral infection

Project description:Chronic viral infections incapacitate adaptive immune responses by 'exhausting' virus-specific T cells, inducing their deletion and reducing productive T cell memory. Viral infection rapidly induces death receptor Fas (CD95) expression by dendritic cells (DCs) making them susceptible to elimination by the immune response. Lymphocytic Choriomeningitis Virus (LCMV) Clone 13, which normally establishes a chronic infection, is rapidly cleared in C57Black/J mice with conditional deletion of Fas in DCs. The immune response to LCMV is characterized by an extended survival of virus-specific effector T cells. Moreover, transfer of Fas-negative DCs from non-infected mice to already-infected animals results in either complete clearance of the virus or a significant reduction of viral titers. Thus, DC-specific Fas expression plays a role in regulation of anti-viral responses and suggests a strategy for stimulation of T cells in chronically infected animals and humans in order to achieve the clearance of persistent viruses. We compared gene expression between splenic DCs from B6.FasKI and B6.CD11c-Cre.FasKI mice. DCs were isolated on day 5 after LCMV infection with 3 mice in each group, for a total of 6 samples. Spleens were collagenase-DNAse digested and sorted by flow to isolate DCs.

2014-05-09 | E-GEOD-57443 | biostudies-arrayexpress

Transcription profiling of mouse IL-12+IL-18 treated and Yersinia enterocolitica infected C57BL/6 NK cells

Project description:Dataset of IL-12+IL-18 trated and Yersinia enterocolitica infected C57BL/6 NK cells Experiment Overall Design: NK cells were isolated from mouse spleen, grown on IL-2 in vitro, stimlated wih Y. enterocolitica WA(pYV) or left uninfected. Experiment Overall Design: 3 conditions, 3 biological replicates each

2009-01-13 | E-GEOD-9735 | biostudies-arrayexpress

Loss of Fas (CD95) expression by dendritic cells protects from a chronic viral infection

2014-05-09 | GSE57443 | GEO

Yakimchuk2019 - Mathematical modeling of immune modulation by glucocorticoids

Project description:Mathematical modeling of immune modulation by glucocorticoids Konstantin Yakimchuk https://doi.org/10.1016/j.biosystems.2019.104066 Abstract The cellular and molecular mechanisms of immunomodulatory actions of glucocorticoids (GC) remain to be identified. Using our experimental findings, a mathematical model based on a system of ordinary differential equations for characterization of the regulation of anti-tumor immune activity by the both direct and indirect GC effects was generated to study the effects of GC treatment on effector CD8+ T cells, GC-generated tolerogenic dendritic cells (DC), regulatory T cells and the growth of lymphoma cells. In addition, we compared the data from in vivo and in silico experiments. The mathematical simulations indicated that treatment with GCs may suppress anti-tumor immune response in a dose-dependent manner. The model simulations were in line with earlier experimental observations of inhibitory effects of GCs on T and NK cells and DCs. The results of this study might be useful for predicting clinical outcomes in patients receiving GC therapy.

2020-01-06 | MODEL1912170005 | BioModels

Small RNA profiling of wildtype and Eri1-deficient mouse T cells

Project description:Natural killer (NK) cells play a critical role in early host defense to infected and transformed cells. Here we show that mice deficient in Eri1, a conserved 3M-bM-^@M-^Y-to-5M-bM-^@M-^Y exoribonuclease that represses RNA interference, have a cell-intrinsic defect in NK cell development and maturation. Eri1M-bM-^@M-^S/M-bM-^@M-^S NK cells displayed delayed acquisition of Ly49 receptors in the bone marrow and a selective reduction in Ly49D and Ly49H activating receptors in the periphery. Eri1 was required for immune-mediated control of mouse cytomegalovirus (MCMV) infection. Ly49H+ NK cells deficient in Eri1 failed to expand efficiently during MCMV infection, and virus-specific responses were also diminished among Eri1M-bM-^@M-^S/M-bM-^@M-^S T cells. We identified miRNAs as the major endogenous small RNA target of Eri1 in mouse lymphocytes. Both NK and T cells deficient in Eri1 displayed a global, sequence-independent increase in miRNA abundance. Ectopic Eri1 expression rescued defective miRNA expression in mature Eri1M-bM-^@M-^S/M-bM-^@M-^S T cells. Thus, mouse Eri1 regulates miRNA homeostasis in lymphocytes and is required for normal NK cell development and anti-viral immunity. Small RNA profiling from wildtype and Eri1-deficient mouse CD4+ T cells

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