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Human monocyte activation with NOD2L vs. TLR2/1L

ABSTRACT: human blood monocytes were isolated, activated and harvested at several timepoints In this study, we identified genes that were differentially expressed in human monocytes activated with eiter NOD2L and/or TLR2/1L.

ORGANISM(S): Homo sapiens

PROVIDER: GSE34156 | GEO | 2012/03/15

SECONDARY ACCESSION(S): PRJNA150053

REPOSITORIES: GEO

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Human monocyte activation with NOD2L vs. TLR2/1L

Project description:human blood monocytes were isolated, activated and harvested at several timepoints In this study, we identified genes that were differentially expressed in human monocytes activated with eiter NOD2L and/or TLR2/1L. human blood monocytes were purified from healthy donors by Ficoll, Percoll and adherence. Monocytes were activated using NOD2L (MDP) and the TLR2/1L (19kD, triacylated peptide). Cells were harvested before activation (0h) and 6h and 24h after stimulation with ligands.

2012-03-15 | E-GEOD-34156 | biostudies-arrayexpress

Transcription profiling of human TLR2/1 stimulated human monocytes with the Mycobacterium tuberculosis derived 19kDa lipopeptide reveals Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

Project description:In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection. Experiment Overall Design: The monocyte microarrays were generated using primary human monocytes stimulated with a TLR2/1L or media at 0, 3, 6, 12, 24 hour timepoints. A total of 10 donors were used with time 0 h samples prepared for each. For time points, we used cells from 4 of the 10 donors to prepare media and TLR2/1-stimulated samples. Experiment Overall Design: Dendritic cells were generated by culturing primary human monocytes with GM-CSF (800 U/ml) and IL-4 (1000 U/ml) for 7 days. The cells were then harvested and recultured for 12 hours with TLR2/1L or media. A total of four donors were used. Experiment Overall Design: See manuscript for specific details on data analysis and experimental design and reagents.

2008-06-17 | E-GEOD-8921 | biostudies-arrayexpress

Beyond Pattern Recognition: TLR2 Promotes Chemotaxis, Cell Adhesion and Migration in THP-1 Cells

Project description:The interaction between monocytes and endothelial cells in inflammation is central to chemoattraction, adhesion, and transendothelial migration. Key players such as selectins and their ligands, integrins and other adhesion molecules and their function in these processes are well studied. Toll-like receptor 2 (TLR2), expressed on monocytes, is critical for sensing invading pathogens and initiating a rapid and effective immune response. However, the extended role of TLR2 in monocyte adhesion and migration has only been partially elucidated. To address this question, we performed several functional cell-based assays using monocyte-like wild type (WT), TLR2-knock-out (KO) and, TLR2-knock-in (KI) THP-1 cells. We found that TLR2 promotes faster and stronger adhesion of monocytes to the endothelium and a more intense endothelial barrier disruption after endothelial activation. In addition, we performed quantitative mass-spectrometry, STRING protein analysis, and RT-qPCR, which revealed the association of TLR2 with specific integrins, but also uncovered novel proteins affected by TLR2. In conclusion, we could show that unstimulated TLR2 affects cell adhesion, endothelial barrier disruption, migration, and actin polymerization.

2023-10-24 | PXD041819 | Pride

Human dendritic cell microRNA profile after NOD2 and / or TLR2 stimulation

Project description:microRNA expression in human monocyte-derived DCs following stimulation with NOD2 ligand MDP, TLR2 ligand Pam3CSK4, or both. 4 condition experiment with two timepoints, and 4 biological replicates. Conditions: unstimulated; MDP stimulated; Pam3CSK4 stimulated; MDP + Pam3CSK4 stimulated. Timepoints: 4 hours and 24 hours.

2013-06-01 | E-GEOD-44785 | biostudies-arrayexpress

TLR2 dimerization blockade allows generation of homeostatic intestinal macrophages under acute colitis challenge

Project description:Recruited blood monocytes contribute to the establishment, perpetuation and resolution of tissue inflammation. Specifically, in the inflamed intestine, monocyte ablation was shown to ameliorate colitis scores in preclinical animal models. However, the majority of intestinal macrophages that seed the healthy gut are also monocyte-derived. Monocyte ablation aimed to curb inflammation would therefore likely interfere with intestinal homeostasis. Here, we used a TLR2 trans-membrane peptide which blocks TLR2 dimerization that is critical for TLR2 /1 and TLR2 / 6 heterodimer signaling to blunt inflammation in a murine colitis model. We show that while the TLR2 peptide treatment ameliorated colitis, it allowed recruited monocytes to give rise to macrophages that lack the detrimental pro-inflammatory gene signature and reduced potentially damaging neutrophils infiltrates. Finally, we demonstrate TLR blocking activity of the peptide on in vitro cultured human monocyte-derived macrophages. Collectively, we provide a significantly improved anti-inflammatory TLR2 peptide and critical insights in its mechanism of action towards future potential use in the clinic.

2019-11-24 | GSE140788 | GEO

RANK+TLR2+ Myeloid Subpopulation Converts Autoimmune to Joint Destruction in Rheumatoid Arthritis

Project description:Joint destruction is the major clinic burden in patients with rheumatoid arthritis (RA). It is unclear, though, how this autoimmune disease progresses to the point of deterioration of the joint. Here, we report that in a mouse model of RA the upregulation of TLR2 expression and its a(2,3) sialylation in RANK+ myeloid monocytes mediate the transition from autoimmunity to osteoclast fusion and bone resorption, resulting in joint destruction. The expression of a(2,3) sialyltransferases were significantly increased in RANK+TLR2+ myeloid monocytes, and their inhibition or treatment with a TLR2 inhibitor blocked osteoclast fusion. Notably, analysis of our single-cell RNA-sequencing (scRNA-seq) libraries generated from RA mice revealed a novel RANK+TLR2- subset that negatively regulated osteoclast fusion. Importantly, the RANK+TLR2+ subset was significantly diminished with the treatments. Moreover, the RANK+TLR2- subset could differentiate into a TRAP+ osteoclast lineage, but the resulting cells did not fuse to form osteoclasts. Our scRNA-seq data showed that Maf is highly expressed in the RANK+TLR2- subset, and the a(2,3) sialyltransferase inhibitor induced Maf expression in the RANK+TLR2+ subset. The identification of a RANK+TLR2- subset provides a potential explanation for TRAP+ mononuclear cells in bone and their anabolic activity. Further, TLR2 expression and its a(2,3) sialylation in the RANK+ myeloid monocytes could be effective targets to prevent autoimmune-mediated joint destruction.

2023-05-24 | GSE221704 | GEO

Transcriptome analysis of TLR2-activated Th17 cells

Project description:Transcriptome analysis of TLR2-activated Th17 cells

| PRJNA730008 | ENA

Profiling of gene expression in TLR2 and TLR3 activated macrophages

Project description:We have identified more than 50 genes that have upregulated expression in TLR3 activated (PMI-1,2), but have downregulated expression in TLR2 activated (PMP-1,2) macrophages, as compared to control cells (PMC-1,2) identify genes that have upregulated expression in TLR3 activated (PMI-1,2), but have downregulated expression in TLR2 activated (PMP-1,2) macrophages, as compared to control cells (PMC-1,2)

2012-03-27 | E-GEOD-36891 | biostudies-arrayexpress

TLR2/1 ligand and IFN-g inducible genes in human monocyte-derived macrophages (MDMs)

Project description:Transcriptome profiles for innate and adaptive immune stimuli important for host response against mycobacteria. Human monocyte-derived macrophages were stimulated with TLR2/1 ligand and interferon-g, stimuli present during innate and adaptive immune responses, respectively.

2016-06-08 | GSE82227 | GEO

Single Cell RNA sequencing of TLR9 ligand (CpG oligonucleotide) and TLR2/4 ligand (LPS)-treated mouse gingiva

Project description:Purpose: The goal of this study was to characterize the gingival oral barrier immunity of TLR9 ligand (CpG oligonucleotide) and TLR2/4 ligand (LPS)-treated mouse maxilla. Method: TLR9 ligand or TLR2/4 ligand was topically applied to the mouse palatal gingiva. Mouse palatal gingiva was harvested at 4 days after topical application. Gingival cells were harvested and subjected to 10X Genomix scRNA-seq. Cell Ranger processed data were analysed.

2022-04-21 | GSE201109 | GEO

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