Ontology highlight
ABSTRACT:
PROVIDER: PRJNA672131 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12936069_1.fastq.gz | Fastqsanger.gz | |||
| SRR12936069_2.fastq.gz | Fastqsanger.gz | |||
| SRR12936070_1.fastq.gz | Fastqsanger.gz | |||
| SRR12936070_2.fastq.gz | Fastqsanger.gz | |||
| SRR12936071_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:We hypothesize that human RIPK3 deficiency does not result in impairment of type I IFN mediated antiviral immunity, contrasting with the situation in deficiencies of the TLR3-IFNAR1 circuit. To test the cellular responses to HSV1 at the wide transcriptome level, bulk RNA sequencing was performed with human primary fibroblasts without or with HSV-1 infection for 24 hours, in cells from healthy controls, RIPK3 HSE patient and other patients with recessive TLR3, IFNAR1 or NEMO deficiency.
2023-03-29 | GSE228495 | GEO
Project description:In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of the TLR3- and UNC-93B-dependent induction of IFN-α/β and/or IFN-λ immunity are prone to HSV-1 encephalitis (HSE) 1-3. The cells responsible for HSE in these children have yet to be identified. We tested the hypothesis that the pathogenesis of HSE involves non hematopoietic central nervous system (CNS)-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were allowed to differentiate into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of IFN-β and/or IFN-λ1 in response to poly(I:C) stimulation was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. The rescue of UNC-93B-deficient cells with the wild-type UNC93B1 allele demonstrated the genetic defect as the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was further rescued by treatment with exogenous IFN-α/β, but not IFN-λ1. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection, a phenotype rescued by wild-type TLR3. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3 pathway deficiencies One human ESC line (H9) was differentiated into 4 different cell types, neural rosettes, CNS neurons, astrocytes and immature oligodendrocytes. Rosettes were purified manually, neurons were sorted negatively for the surface markers EGFR and CD44, oligodendrocyte cells were positively sorted for the surface marker O4 while astrocytes were enriched by growth in serum containing medium. All cell types were subjected to RNA extraction and hybridization on Illumina microarrays. Each sample has 3 biological repeats, except rosettes which has 2 repeats. In a seperate experiement, undifferentiated H9 cells along with H9-derived neurons and astrocyes as well as UNC93B-/- iPS derived neurons and astrocytes were also subjected to RNA extraction and hybridization on Illumina microarrays.
2012-11-29 | E-GEOD-40593 | biostudies-arrayexpress
Project description:In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of the TLR3- and UNC-93B-dependent induction of IFN-α/β and/or IFN-λ immunity are prone to HSV-1 encephalitis (HSE) 1-3. The cells responsible for HSE in these children have yet to be identified. We tested the hypothesis that the pathogenesis of HSE involves non hematopoietic central nervous system (CNS)-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were allowed to differentiate into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of IFN-β and/or IFN-λ1 in response to poly(I:C) stimulation was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. The rescue of UNC-93B-deficient cells with the wild-type UNC93B1 allele demonstrated the genetic defect as the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was further rescued by treatment with exogenous IFN-α/β, but not IFN-λ1. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection, a phenotype rescued by wild-type TLR3. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3 pathway deficiencies
2012-11-29 | GSE40593 | GEO
Project description:We have performed microarray expression profiling of mouse primary neurons (cortical neurons and granule cell neurons) to model molecular networks and define whether distinct antiviral IFN responses occurred in neurons corresponding to different brain regions. Primary mouse cortical neurons and granule cell neurons were left untreated, treated with 100IU/mL of IFN-M-NM-2, or infected with West Nile virus (MOI of 1) and RNA was harvested after 24 hours. Three independent experiments were performed using a balanced design.
2012-12-05 | E-GEOD-42727 | biostudies-arrayexpress
Project description:Microarray expression profilling of mouse primary mixed cortical/hippocampal neurons, primary fibroblasts and L929 cells to compare ISGs signature in disctinct cell types Primary mixed cortical/hippocampal neurons, primary fibroblasts (MEFs) and L929 cells were mock-treated or treated with 5U/mL of IFN-beta and RNA was harvested after 24 hours. For neurons and fibroblast, 2 samples were analyzed for each condition.
2014-01-10 | E-GEOD-53951 | biostudies-arrayexpress
Project description:Effective anti-viral immunity depends on the ability of infected cells or cells triggered with virus-derived nucleic acids to produce type I interferon (IFN), which activates transcription of numerous antiviral genes. However, disproportionately strong or chronic IFN expression is a common cause of inflammatory and autoimmune diseases. Here we describe an epigenetic mechanism that determines cell-type specific differences in IFN and IFN-stimulated gene expression in response to exogenous signals. We identify di-methylation of histone H3 at lysine 9 (H3K9me2) as a suppressor of IFN and IFN-inducible antiviral gene expression. We show that levels of H3K9me2 at IFN and IFN stimulated genes (ISG) correlate inversely with the scope and amplitude of IFN and ISG expression in fibroblasts and dendritic cells. Accordingly, genetic ablation or pharmacological inactivation of lysine methyltransferase G9a, which is essential for the generation of H3K9me2, resulted in phenotypic conversion of fibroblasts into highly potent IFN-producing cells and rendered these cells resistant to pathogenic RNA viruses. In summary, our studies implicate H3K9me2 and enzymes controlling its abundance as key regulators of innate antiviral immunity. Examination of epigenetic modifications in WT and G9a deficient MEFs and splenic DCs
2012-03-02 | E-GEOD-22102 | biostudies-arrayexpress
Project description:Effective anti-viral immunity depends on the ability of infected cells or cells triggered with virus-derived nucleic acids to produce type I interferon (IFN), which activates transcription of numerous antiviral genes. However, disproportionately strong or chronic IFN expression is a common cause of inflammatory and autoimmune diseases. Here we describe an epigenetic mechanism that determines cell-type specific differences in IFN and IFN-stimulated gene expression in response to exogenous signals. We identify di-methylation of histone H3 at lysine 9 (H3K9me2) as a suppressor of IFN and IFN-inducible antiviral gene expression. We show that levels of H3K9me2 at IFN and IFN stimulated genes (ISG) correlate inversely with the scope and amplitude of IFN and ISG expression in fibroblasts and dendritic cells. Accordingly, genetic ablation or pharmacological inactivation of lysine methyltransferase G9a, which is essential for the generation of H3K9me2, resulted in phenotypic conversion of fibroblasts into highly potent IFN-producing cells and rendered these cells resistant to pathogenic RNA viruses. In summary, our studies implicate H3K9me2 and enzymes controlling its abundance as key regulators of innate antiviral immunity. Examination of gene expression in response to PolyI:C in WT and G9a deficient DCs
2012-03-02 | E-GEOD-24774 | biostudies-arrayexpress
Project description:Effective anti-viral immunity depends on the ability of infected cells or cells triggered with virus-derived nucleic acids to produce type I interferon (IFN), which activates transcription of numerous antiviral genes. However, disproportionately strong or chronic IFN expression is a common cause of inflammatory and autoimmune diseases. Here we describe an epigenetic mechanism that determines cell-type specific differences in IFN and IFN-stimulated gene expression in response to exogenous signals. We identify di-methylation of histone H3 at lysine 9 (H3K9me2) as a suppressor of IFN and IFN-inducible antiviral gene expression. We show that levels of H3K9me2 at IFN and IFN stimulated genes (ISG) correlate inversely with the scope and amplitude of IFN and ISG expression in fibroblasts and dendritic cells. Accordingly, genetic ablation or pharmacological inactivation of lysine methyltransferase G9a, which is essential for the generation of H3K9me2, resulted in phenotypic conversion of fibroblasts into highly potent IFN-producing cells and rendered these cells resistant to pathogenic RNA viruses. In summary, our studies implicate H3K9me2 and enzymes controlling its abundance as key regulators of innate antiviral immunity. Examination of gene expression in response to PolyI:C in WT and G9a deficient MEFs
2012-03-02 | E-GEOD-24776 | biostudies-arrayexpress
Project description:We have performed microarray expression profiling of mouse primary neurons (cortical neurons and granule cell neurons) to model molecular networks and define whether distinct antiviral IFN responses occurred in neurons corresponding to different brain regions.
2012-12-05 | GSE42727 | GEO
Project description:<p>Healthy behavioral patterns could modulate organ functions to enhance the body’s immunity. However, whether exercise regulates antiviral innate immunity remains elusive. Here, we found that exercise promotes type-I IFN (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could regulate IFN-I production, we identified Gpld1 as a crucial molecule and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1-/- mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction and therefore enhances IRF3 activation and IFN-I production, and improves the body’s antiviral ability. This study reveals that the exercise behavior improves antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity, and uncovers an unknown function of liver cells in innate immunity.</p>
2024-04-24 | MTBLS7972 | MetaboLights