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Treatment of human monocytes with TLR7 or TLR8 agonists

ABSTRACT: Goal was to detect differences in response to TLR7 versus TLR8 agonists in human monocytes from healthy donors

ORGANISM(S): Homo sapiens

PROVIDER: GSE64480 | GEO | 2014/12/24

SECONDARY ACCESSION(S): PRJNA271093

REPOSITORIES: GEO

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Treatment of human monocytes with TLR7 or TLR8 agonists

Project description:Goal was to detect differences in response to TLR7 versus TLR8 agonists in human monocytes from healthy donors 3 deidentified donors from the Red Cross, monocytes from each donor incubated overnight with either vehicle, TLR7 agonist or TLR8 agonist

2014-12-24 | E-GEOD-64480 | biostudies-arrayexpress

UNC93B1 variants underlie TLR7-dependent autoimmunity

Project description:UNC93B1 is critical for trafficking and function of nucleic acid-sensing Toll-like receptors (TLRs) TLR3, TLR7, TLR8, and TLR9, which are essential for antiviral immunity. Overactive TLR7 signaling induced by recognition of self-nucleic acids has been implicated in systemic lupus erythematosus (SLE). Here, we report UNC93B1 variants (E92G and R336L) in four patients with early-onset SLE. Patient cells or mouse macrophages carrying the UNC93B1 variants produced high amounts of TNF-α and IL-6 and upon stimulation with TLR7/TLR8 agonist, but not with TLR3 or TLR9 agonists. E92G causes UNC93B1 protein instability and reduced interaction with TLR7, leading to selective TLR7 hyperactivation with constitutive type I IFN signaling. Thus, UNC93B1 regulates TLR subtype-specific mechanisms of ligand recognition. Our findings establish a pivotal role for UNC93B1 in TLR7-dependent autoimmunity and highlight the therapeutic potential of targeting TLR7 in SLE.

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Next Generation Sequencing for Quantitative Transcriptomic Profiling of TLR3, TLR7 and TLR8 Activation in Neurons

Project description:The goal of this study is to compare gene expression of mouse cultured cortical and hippocampal neurons in response to TLR3, TLR7 and TLR8 activation

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Homo sapiens

Project description:Treatment of human monocytes with TLR7 or TLR8 agonists

| PRJNA271093 | ENA

Quantitative Analysis of CXCL4 and TLR8 signaling crosstalk in human primary monocytes by RNA-Seq

Project description:To gain a comprehensive understanding of gene regulation in CXCL4 and TLR8 signaling crosstalk, we treated primary human blood monocytes with CXCL4 and TLR8 ssRNA ligand ORN8L for 6 h and performed transcriptomic analysis via RNA-seq. We observed that CXCL4 interacted with TLR8 ssRNA ligand and triggered inflammatory cytokine storm including IL6, IL12p40, TNF and IFNβ, and pro-fibrotic gene expression and activated NLRP3 inflammasome leading to interleukin-1β (IL-1β) secretion and pyroptosis in human blood monocytes.

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TLR agonists on human dendritic cells

Project description:Toll like receptors (TLRs) sense microbial products and initiate adaptive immune responses by activating dendritic cells (DCs). Since pathogens may contain several agonists we asked whether different TLRs may synergize in DC activation. We report that in human and mouse DC TLR3 or TLR4 potently synergize with TLR7, TLR8 or TLR9 in the induction of selected cytokine genes. Upon synergistic stimulation, IL-12, IL-23 and Delta-4 are induced at levels 50-100 fold higher than those induced by optimal concentrations of single agonists, leading to enhanced and sustained TH1 polarizing capacity. Using microarray analysis we show that only 1.5% of the transcripts induced by single TLR agonists are synergistically regulated by combinations of TLR4 and TLR8 agonists.. These results identify a combinatorial code by which DCs discriminate pathogens and provide (suggest) a rationale to design adjuvants for TH1 responses. Series_overall_design: 3 untreated, 3 treated with LPS at 2h, 3 treated with LPS at 8h, 3 treated with R848 at 2h, 3 treated with R848 at 8h, 3 treated with LPS + R848 at 2h, 3 treated with LPS + R848 at 8h Keywords: other

2005-09-01 | GSE2706 | GEO

RIPK3 negatively regulates the (CXCL4+TLR8)-induced IFN response while promoting NLRP3 inflammasome activation in human monocytes

Project description:To investigate the function of RIPK3 in regulation of IFN response and inflammatory response in human monocytes stimulated with CXCL4 and TLR8, We blocks (CXCL4 + TLR8)-induced pyroptosis and RIPK3 activation using necrosulfonamide (NSA, 5 µM) and GSK'872 (10 µM) and measure gene expression genome-wide with RNA-seq.

2023-04-30 | GSE201909 | GEO

Whole-Genome Gene Expression Bead Array analysis of Toll-like receptor 2/8 stimulated human monocytes

Project description:Monocytes and macrophages are essential cells in the early response in their capacity as ubiquitous phagocytic cells. They phagocytose microorganisms or damaged cells and sense pathogen/damage-associated molecular patterns (PAMPs/DAMPs) through innate receptors such as Toll-like receptors (TLRs). We investigated a phenomenon where co-signaling from TLR2 and TLR8 in human primary monocytes provides a distinct immune activation profile compared to signaling from either TLR alone. Comparison of gene signatures induced by either stimulus alone or together, show that co-signaling result in downstream differences in regulation of signaling and gene transcription. To investigate the interaction of TLR2 and TLR8 stimulation primary human monocytes isolated from buffy coat were stimulated with TLR2/6 ligand FSL-1 and/or TLR7/8 ligand CL075 and the gene expression monitored at 1,2 and 3h post stimulation.

2018-03-09 | E-MTAB-6222 | biostudies-arrayexpress

BCR repertoire analysis by Next-generation sequencing of lymphocytes harvested from mice vaccinated with liposomal TLR4 and TLR7 agonists

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2021-03-01 | E-MTAB-8870 | biostudies-arrayexpress

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