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GSE99841
Mus musculus, Homo sapiens
9 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Epigenetic regulation is based upon a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets to treat a range of diseases including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach to control infection, persistence, and the resulting recurrent disease. The histone methyltransferases EZH2 and EZH1 (EZH2/1) are epigenetic repressors that suppress gene transcription via propagation of repressive H3K27me3 enriched chromatin domains. However, while EZH2/1 are implicated in repression of herpesviral gene expression, inhibitors of these enzymes suppressed HSV primary infection in vitro and in vivo. Furthermore, these compounds blocked lytic viral replication following induction of HSV reactivation in latently infected sensory ganglia. Suppression correlated with the induction of multiple inflammatory, stress, and anti-pathogen pathways as well as enhanced recruitment of immune cells to in vivo infection sites. Importantly, EZH2/1 inhibitors induced a cellular antiviral state that also suppressed infection with DNA (hCMV, Adenovirus) and RNA (Zika virus) viruses. Thus, EZH2/1 inhibitors have considerable potential as general antivirals through activation of cellular antiviral and immune responses.
Publication Title
Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 102 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Malaria is a disease with diverse symptoms depending on host immune status and pathogenicity of Plasmodium parasites. The continuous parasite growth within a host suggests mechanisms of immune evasion and/or inhibition. To identify pathways commonly inhibited by malaria infection, we infected C67BL/6 mice with four Plasmodium yoelii strains causing different disease phenotypes and 24 progeny of a genetic cross. mRNAs from mouse spleens day 1 and/or day 4 post infection (p.i.) were hybridized to a mouse microarray to identify activated or inhibited pathways, upstream regulators, and linkages to parasite genetic loci. Strong interferon responses were observed after infection with N67 strain, whereas initial inhibition and later activation of hematopoiesis pathways were found after infection with 17XNL parasite. Inhibition of pathways such as Th1 activation, dendritic cell (DC) maturation, and NFAT immune regulation were observed in mice infected with all the parasite strains day 4 p.i., suggesting universally inhibited immune pathways. Treatment of infected mice with antibodies against T cell receptors OX40 or CD28 to activate malaria-inhibited pathways enhanced host survival. Controlled activation of these pathways may provide important strategies for better disease management and for developing an effective vaccine.
Publication Title
Detection of host pathways universally inhibited after Plasmodium yoelii infection for immune intervention.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 81 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
An invading pathogen will trigger specific host responses, which can be explored to identify genes functioning in pathogen recognition and elimination. Here we performed trans-species expression quantitative trait locus (ts-eQTL) analysis using genotypes of the Plasmodium yoelii malaria parasite and phenotypes of mouse gene expression. We significantly (LOD score3.0) linked 1,054 host genes to many parasite genetic loci. Clustering genome-wide pattern of LOD scores (GPLSs), which produced results different from those of direct expression level clustering, grouped host genes functioning in related pathways together, allowing accurate functional prediction of unknown genes. As proof of principle, 14 of 15 randomly selected genes unknown, but predicted to function in type I interferon (IFN-I) responses, were experimentally verified using gene over expression, shRNA knockdown, viral infection, and/or infection of KO mice. This study demonstrates an effective strategy for studying gene function, establishes a functional gene database, and identifies regulators in IFN-I pathways.
Publication Title
Genome-wide Analysis of Host-Plasmodium yoelii Interactions Reveals Regulators of the Type I Interferon Response.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 69 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
Gene expression kinetics for BM-DM from C57BL/6 mouse stimulated with four different TLR ligands poly(I:C), R848, LPS, Pam3CSK4 either singly or in paired combination, for 1 hour, 4 hour, or 8 hour.
Publication Title
Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 66 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 47 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
Gene expression kinetics for BM-DM from C57BL/6 mice challenged by poly(I:C) , R848, poly(I:C)+R848 examined at 6 time points including 0.5, 1, 2, 4, 8, 12 h.
Publication Title
Systematic Investigation of Multi-TLR Sensing Identifies Regulators of Sustained Gene Activation in Macrophages.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 36 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Glutamine supplementation suppresses herpes simplex virus reactivation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 27 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Mycobacterium tuberculosis infection (Mtb) is the leading cause of death due to a single infectious agent and among the top ten causes of all human death worldwide1. CD4 T cells are essential for resistance to Mtb infection, and for decades it has been thought that IFN production is the primary mechanism of CD4 T cell-mediated protection2,3. However, IFN responses do not correlate with host protection, and several reports have demonstrated that additional anti-tuberculous CD4 T cell effector functions remain unaccounted for4-8. Here we show that the TNF superfamily molecule CD153 (TNFSF8) is required for IFN-independent control of pulmonary Mtb infection by CD4 T cells. In Mtb infected mice, CD153 expression is highest on Ag-specific Th1 cells in the lung tissue parenchyma, but its induction does not require Th1 polarization. CD153 deficient mice develop high pulmonary but not splenic bacterial loads and succumb early to Mtb infection. Reconstitution of T cell-deficient hosts with either CD153-/- or IFN-/- CD4 T cells fails to rescue mice from early mortality, but reconstitution with a mixture of CD153-/- and IFN-/- CD4 T cells provides similar protection as WT T cells. In Mtb infected non-human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the airways compared to the blood, and the frequency of Mtb-specific CD153-expressing CD4 T cells inversely correlates with bacterial loads in granulomas. In Mtb infected humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells that are much more abundant in individuals with controlled latent Mtb infection compared to those with active TB. In all three species, Mtb-specific CD8 T cells did not upregulate CD153 following peptide stimulation. Thus, we have identified expression of CD153 by CD4 T cells as a major immune mechanism of host protection against pulmonary Mtb infection.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
The innate immune system is the organisms first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level.
Publication Title
Proteome and Secretome Analysis Reveals Differential Post-transcriptional Regulation of Toll-like Receptor Responses.
Sample Metadata Fields
Specimen part, Cell line
View Samples