Immune Response of Immature Dendritic Cells after Infection with Human Cytomegalovirus Strain TB40E
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE14816 | GEO | 2009/08/01
SECONDARY ACCESSION(S): PRJNA112055
REPOSITORIES: GEO
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Project description:Microarray analysis and quantitative real-time PCR revealed that TB40E infection of DCs led to changes of the gene expression pattern. A variety of pro-inflammatory cytokines and chemokines (CXCL10, CXCL11, CCL5), TLR3 and genes whose products function downstream of the TLR3 signalling pathway (e.g. IFN-alpha, IFN-beta) were significantly upregulated. Three mock transfected DC vs. three TB40 transfected DCs
2009-08-01 | E-GEOD-14816 | biostudies-arrayexpress
Project description:Chemokines are chemotactic cytokines that control the migratory patterns and positioning of immune cells. Many chemokines have been associated with systemic autoimmune diseases that have chronic IFN signature. We now describe that a series of chemokines, including CXCL4, CXCL10, CXCL12 and CCL5, can superinduce type I IFN (IFN-I) by TLR9-activated plasmacytoid DCs (pDCs), independently of their respective known chemokine receptors. Mechanistically, we show that chemokines such as CXCL4 mediate transcriptional and epigenetic changes in pDCs, mostly targeted to the IFN-I pathways. We also describe that chemokines physically interact with DNA to form nanoparticles which promote clathrin-mediated cellular uptake and delivery of DNA in the early endosomes of pDCs. Using two mouse models of skin inflammation, we observed the presence of CXCL4 associated with DNA in vivo. These data thus reveal a non-canonical role for chemokines to modulate TLR signaling, and extend our understanding on the mechanism associated with the chronic expression of IFN-I by pDCs in autoimmune diseases.
2022-05-24 | GSE202333 | GEO
Project description:To identify the immunological status of the persistent and chronic stages, we analysed immunological genes in lung tissues from mice infected with M. tuberculosis. Based on the cDNA microarray results, 11 candidate cytokine genes, which were obviously up-regulated during the chronic stage compared with those during the persistent stage, were selected and clustered into three groups: 1) chemokine genes, except those of monocyte chemoattractant proteins (MCPs) (CXCL9, CXCL10, CXCL11, CCL5, CCL19); 2) MCP genes (CCL2, CCL7, CCL8, CCL12); and 3) TNF and IFN-γ genes. Results from the cDNA microarray and quantitative RT-PCR analyses revealed that the mRNA expression of the selected cytokine genes was significantly higher in lung tissues of the chronic stage than of the persistent stage. Three chemokines (CCL5, CCL19 and CXCL9) and three MCPs (CCL7, CCL2 and CCL12) were noticeably increased in the chronic stage compared with the persistent stage.
2017-04-15 | GSE97835 | GEO
Project description:Abstract Background: Dendritic cells (DCs) are often produced by granulocyte-macrophage colony-stimulating factor (GMCSF) and interleukin-4 (IL-4) stimulation of monocytes. To improve the effectiveness of DC adoptive immune cancer therapy, many different agents have been used to mature DCs. We analyzed the kinetics of DC maturation by lipopolysaccharide (LPS) and interferon-g (IFN-g) induction in order to characterize the usefulness of mature DCs (mDCs) for immune therapy and to identify biomarkers for assessing the quality of mDCs. Methods: Peripheral blood mononuclear cells were collected from 6 healthy subjects by apheresis, monocytes were isolated by elutriation, and immature DCs (iDCs) were produced by 3 days of culture with GM-CSF and IL-4. The iDCs were sampled after 4, 8 and 24 hours in culture with LPS and IFN-g and were then assessed by flow cytometry, ELISA, and global gene and microRNA (miRNA) expression analysis. Results: After 24 hours of LPS and IFN-g stimulation, DC surface expression of CD80, CD83, CD86, and HLA Class II antigens were up-regulated. Th1 attractant genes such as CXCL9, CXCL10, CXCL11 and CCL5 were up-regulated during maturation but not Treg attractants such as CCL22 and CXCL12. The expression of classical mDC biomarker genes CD83, CCR7, CCL5, CCL8, SOD2, MT2A, OASL, GBP1 and HES4 were up-regulated throughout maturation while MTIB, MTIE, MTIG, MTIH, GADD45A and LAMP3 were only up-regulated late in maturation. The expression of miR-155 was up-regulated 8-fold in mDCs. Conclusion: DCs, matured with LPS and IFN-g, were characterized by increased levels of Th1 attractants as opposed to Treg attractants and may be particularly effective for adoptive immune cancer therapy.
2018-03-08 | GSE111581 | GEO
Project description:Plasmacytoid dendritic cells (pDCs) play a critical role in bridging the innate and adaptive immune systems. pDCs are specialized type I interferon (IFN) producers, which has implicated them as initiators of autoimmune pathogenesis. However, little is known about the down-stream effectors of type I IFN signaling that amplify autoimmune responses. Here we have used a chemokine reporter mouse to determine the CXCR3 ligand responses in DCs subsets. Following TLR7 stimulation conventional type 1 and type 2 DCs (cDC1 and cDC2 respectively) uniformly upregulate CXCL10. By contrast, the proportion of chemokine positive pDCs was significantly less, and stable CXCL10+ and CXCL10 - populations could be distinguished. CXCL9 expression was induced in all cDC1s, in half of the cDC2 but not by pDCs. In all DC subsets, type I IFNs were the main inducer of CXCR3 chemokines, as IFNAR receptor blocking or deficiency completely abrogated reporter expression. Chemoki ne producing potential was not concordant with the previously identified markers of pDC heterogeneity. Finally, we show that CXCL10+ and CXCL10 - populations are transcriptionally distinct, expressing unique transcriptional regulators, IFN signaling molecules, chemokines, cytokines and cell surface markers. This work highlights CXCL10 as a downstream effector of type I IFN signaling and suggests a division of labor in pDCs subtypes that likely impacts their function as effectors of viral responses and as drivers of inflammation.
2018-06-24 | GSE113770 | GEO
Project description:G protein-coupled receptors (GPCRs) interact with many transducers like G proteins and β-arrestins. Some GPCR agonists act as “biased agonists” which preferentially activate specific signaling transducers over others, leading to unique signaling profiles. The chemokine system, a subfamily of GPCRs that plays a critical role in inflammatory diseases, serves as an endogenous example of biased agonism where over 50 different chemokines ligands and 20 receptors interact promiscuously. In this study, we sought to determine the three different chemokines of the chemkoine receptor CXCR3 generate different transcriptional responses in primary CD8+ T cells. Using RNAseq on CD8+ T cells stimulated with either vehicle control, CXCL9, CXCL10, or CXCL11, the endogenous chemokines of CXCR3, we found that the CXCR3 chemokines promoted unique transcriptional responses that are predicted to differentially regulate inflammatory pathways. We observed significant changes in global transcriptional activation, detecting approximately 48000 transcripts, 887 of which varied by chemokine treatment. There was a high degree of replicability between biological replicates. The overwhelming majority of differentially expressed genes (DEGs) increased in transcript level following chemokine treatment. Compared to vehicle control, CXCL11 demonstrated the largest number of DEGs. Importantly, CXCL11 and CXCL10 demonstrate unique transcriptional profiles where the majority of DEGs were only found following treatment with each specific chemokine, rather than being shared across chemokines. These data contrast with that observed at CXCL9 – although it promoted a significant amount of transcriptional regulation, approximately 66% of CXCL9-induced DEGs were shared with CXCL11 and/or CXCL10.
2022-07-23 | GSE192679 | GEO
Project description:DCs are localized under the mucosa of the lungs and the gastrointestinal tract, and therefore come into close contact with A. fumigatus germ tubes during early steps of infection as soon as fungi become invasive. For a more detailed insight into differentially regulated genes, whole genome microarray analysis was performed. On average, unstimulated DCs showed expression of about 13.500 genes (35% of all genes spotted on the chip). After 6h co-cultivation of DCs and live A. fumigatus germ tubes, 590 genes showed a 4fold altered gene expression, if normalizing data with VSN before. Therein, a wide range of immune response genes, including genes encoding for cytokines (IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, TNF-α), chemokines (CCL5, CCL20, CXCL10), immunorelevant receptors (TLR2, TLR4, PTX-3), as well as costimulatory molecules (CD40, CD80, CD83, CD86) were differentially regulated. Experiment Overall Design: Human DCs were generated from two independent, healthy blood donors. 5 x 106 DCs were either cultivated without fungi or together with 5 x 106 A. fumigatus germ tubes for 6h until isolation of total RNA.
2008-06-15 | E-GEOD-6965 | biostudies-arrayexpress
Project description:We have used chemokine reporter mice to investigate down-stream effectors of type I IFN signaling, the chemokines of the CXCR3 family. We show that pDCs and conventional DCs display unique chemokine expression profiles that are dependent on IFNAR1 signaling. We go onto show that, following stimulation, pDCs form two stable and transcriptionally distinct populations based on their expression of CXCL10.
2019-12-26 | GSE110975 | GEO
Project description:Purpose: To investigate the effects of T cell-derived cytokines on gene and protein expression of chemokines in a human RPE cell line (ARPE-19). Methods: We used an in vitro co-culture system in which the RPE and CD3/28-activated T cells were separated by a membrane. Differential gene expression in the RPE cells of chemokine genes was quantified using three different microarrays. Protein expression was determined by single- and multiplex ELISA and immunoblotting. Results: Co-culture with activated T cells increased RPE mRNA and protein expression of chemokines CCL2 (MCP-1), CCL5 (RANTES), CCL7 (MCP-3), CCL8 (MCP-2), CXCL1 (GRO-α), IL8 (CXCL8), CXCL9 (MIG), CXCL10 (IP10), CXCL11 (ITAC), and CX3CL1 (fractalkine). The secretion of CCL7 and CXCL9, 10, and 11 was polarized in the apical direction. Using recombinant human cytokines and neutralizing antibodies we identified IFNgamma and TNFalpha as the two major T cell-derived cytokines responsible for the RPE response. For CCL5, CXCL9, 10, 11, 16, and CX3CL1 we observed a synergistic effect of IFNgamma and TNFalpha in combination. CCL20, CXCL1 and 6, and IL8 were negatively regulated by IFNgamma. Conclusions: RPE cells responded to exposure to T cell-derived cytokines by upregulating expression of several chemokines related to microglial, T cell, and monocyte chemotaxis and activation. This inflammatory stress response may have implications for immune homeostasis in the retina, and for the further understanding of inflammatory ocular diseases such as uveitis and age-related macular degeneration. Differentiated ARPE19 grown on inserts in serum-free media was basolaterally stimulated for 48h with activated T cells or recombinant cytokines (IFNg and/or TNFa) or neutralizing antibodies (aIFNg and/or aTNFa)
2012-11-19 | E-GEOD-36331 | biostudies-arrayexpress
Project description:Borrelia burgdorferi, the agent of Lyme disease, promotes pro-inflammatory changes in endothelium that lead to the recruitment of leukocytes. The host immune response to infection results in increased levels of IFN-gamma in the serum and lesions of Lyme disease patients that correlate with greater severity of disease. Therefore, the effect of IFN-gamma on the gene expression profile of primary human endothelial cells exposed to B. burgdorferi was determined. B. burgdorferi and IFN-gamma synergistically augmented the expression of 34 genes, seven of which encode chemokines. Six of these (CCL7, CCL8, CX3CL1, CXCL9, CXCL10, and CXCL11) attract T lymphocytes, and one (CXCL2) is specific for neutrophils. Synergistic production of the attractants for T cells was confirmed at the protein level. IL-1beta, TNF-alpha, and LPS also cooperated with IFN-gamma to induce synergistic production of CXCL10 by endothelium, indicating that IFN-gamma potentiates inflammation in concert with a variety of mediators. An in vitro model of the blood vessel wall revealed that an increased number of human T lymphocytes traversed endothelium exposed to B. burgdorferi and IFN-gamma, as compared to unstimulated endothelial monolayers. In contrast, addition of IFN-gamma diminished the migration of neutrophils across B. burgdorferi-activated endothelium. IFN-gamma thus alters gene expression by endothelium exposed to B. burgdorferi in a manner that promotes recruitment of T cells and suppresses that of neutrophils. This modulation may facilitate the development of chronic inflammatory lesions in Lyme disease. Experiment Overall Design: Human umbilical vein endothelial cells (HUVEC) were stimulated with Interferon-gamma (IFN-g), Borrelia burgdorferi or both IFN-g and Borrelia or were left unstimulated. Affymetrix HGU133 plus 2.0 slides were used in duplicate for each condition.
2008-06-14 | E-GEOD-6092 | biostudies-arrayexpress