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Genetic Determinants of Transcriptional Variation in Primary Human Monocytes Across Multiple Contexts

ABSTRACT: Monocytes undergo global gene expression changes upon stimulation, thus a significant proportion of eQTL are specific to activation state. Here we systematically explore determinants of gene and transcript expression in monocytes from 185 individuals in the untreated state and post-exposure to IFNÃŽÂ³ or lipopolysaccharide (LPS).

PROVIDER: EGAS00001007111 | EGA |

REPOSITORIES: EGA

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Staphylococcus aureus Mediated Tolerance Induction in Human Monocytes is accompanied with Specific Alterations in Membrane Receptor Expression

Project description:Exposure of human monocytes to lipopolysaccharide (LPS) or other pathogen-associated molecular pattern (PAMPs) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance (ET). The tolerant state of monocytes is accompanied by cell surface and other glycoprotein expression changes induced by the activation of Toll-like receptors (TLRs). In this study, we aimed to characterize the cellular state of human monocytes stimulated with Gram-positive Staphylococcus aureus and TLR2 ligands. We analyzed gene expression changes induced by S. aureus after 2 and 24 hours by amplicon sequencing (RNA-AmpliSeq) and compared the pro-inflammatory response after 2 hours of stimulation to the to the response in re-stimulation experiments after the first stimulus. In parallel, glycoprotein expression changes in human monocytes after 24 hours of S. aureus stimulation were analyzed by proteomics and compared to stimulation experiments with TLR2 ligands Malp-2 and Pam3Cys and TLR4 ligand LPS. The results demonstrate that monocytes stimulated with S. aureus and TLR ligands entered the tolerant cell state after activation. Compared to TLR agonist mediated activation and tolerization of monocytes, glycoprotein expression changes induced by S. aureus stimulation revealed significant differences in receptor expression profiles. We report a glycoprotein expression profile characteristic for PAMP and S. aureus tolerized human monocytes. Finally, we analyzed peripheral blood monocytes of patients with S. aureus bloodstream infection for inflammatory responses in vitro and for their glycoprotein expression profiles. RNA-AmpliSeq data from patient-derived monocytes demonstrated that the cells were pro-inflammatory responsive to S. aureus stimulation and expressed higher level of CD44 mRNA, while other markers of the tolerant cell state were not detected.

2023-05-10 | PXD036036 | Pride

Transcriptome analysis of in vitro endotoxin tolerant human monocytes

Project description:Monocyte exposure to lipopolysaccharide (LPS) induces a transient state in which these cells are refractory to further endotoxin stimulation. Here we demonstrate the transcriptome analysis of in vitro generated LPS refractory monocytes upon subsequent re-exposure to LPS for different time points.

2009-03-14 | GSE15219 | GEO

Transcriptome analysis of in vitro endotoxin tolerant human monocytes

2009-03-13 | E-GEOD-15219 | biostudies-arrayexpress

Transcriptional profiing of cultured adherent and non-adherent monocytes

Project description:To determine the effect of adherence on the metabolic and functional response of human monocytes. Monocytes were stimulated with lipopolysaccharide (LPS) under non-adherent and adherent conditions. To determine the role of glycolysis in LPS-induced immune responses, this pathway was inhibited by glucose deprivation or the glucose analog 2-deoxy-D-glucose (2DG).

2020-12-08 | GSE161839 | GEO

scRNAseq of monocytes from Trained immunity experiments

Project description:scRNAseq of monocytes from in vitro Trained immunity experiments stimulated by β-glucan (BG), uric acid (UA), muramyl dipeptide (MDP), oxidized low-density lipoprotein (oxLDL), or RPMI-Control, and respective samples restimulated with Lipopolysaccharide (LPS).

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Glycoproteomes of naive and LPS stimulated human monocytes and THP-1 cells

Project description:CD14+ Monocytes from healthy volunteers were purified by MACS (negative selection) and FACSorting and either left untreated or stimulated for 24h and 48h with LPS. THP-1 cells were stimulated for 4h, 24h and 48h with LPS. Glycoproteins were captured with hydrazide chemistry and tryptic and PNGase F-released peptide fractions analyzed by MS/MS. Quantitative assessment revealed differential glycoprotein expression in activated/LPS-tolerized monocytes and naïve monocytes and THP-1 cells.

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Patterns of transcriptional response to 1,25-dihydroxyvitamin D3 and bacterial lipopolysaccharide in primary human monocytes

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Project description:Stroke is a highly prevalent and devastating disease with limited therapeutic options. Most efforts to develop treatments for stroke have thus far met with limited success in large clinical trials. The brain has an enormous capacity for self-preservation, and elucidating how the brain protects itself may provide novel insights into stroke treatment. Ischemic tolerance (IT), a phenomenon in which application of sub-lethal stress [preconditioning (PC) stimulus; PC] induces a state of tolerance to a subsequent ischemic insult, represents an example of endogenous neuroprotection. IT can be induced in brain by systemic administration of the Toll-like receptor-4 ligand lipopolysaccharide (LPS). Different populations of immune cell could potentially play a role in PC induced by LPS. In particular, monocytes, which are the main target of LPS, can exert a powerful protective effect either directly or by modulating the immune system.

2016-07-13 | GSE84327 | GEO

Transcription profiling of human monocytes exposed to lipopolysaccharide or collagen-related peptide to elucidate the transcriptional differences in monocytes responding to either a danger or damage signal

Project description:stimulation of whole blood using 5 ng/ml lipopolysaccharide (LPS, gram -ve bacterial endotoxin) or 5 ug/ml CRP-18 (collagen-related peptide; GPO-18). Monocytes respond to stimuli differently. This experiment was designed to elucidate the transcriptional differences in monocytes responding to either a danger signal (supplied by LPS) or a damage signal (supplied by CRP-18). CRP-18 is a collagen mimetic and was used to represent collagen exposure at sites of vessel damage. Exposed collagen activates platelts which in turn activate monocytes. The transcriptional differences which ensue are not known yet and were investigated in this work.

2010-01-01 | E-TABM-483 | biostudies-arrayexpress

GM-CSF Production by Non-Classical Monocytes Controls Antagonistic LPS-driven Functions In Allergic Inflammation

Project description:Lipopolysaccharide (LPS) can either promote or prevent T helper-2 (Th2) cell-allergic responses. However, the underlying mechanism remains unknown. We show here that LPS activity switches from pro-pathogenic to protective depending on the production of GM-CSF by non-classical monocytes. In the absence of GM-CSF, LPS can favor pathogenic Th2 cell responses by supporting the trafficking of lung migratory dendritic cells (mDC2s) into the lung-draining lymph node. However, when non-classical monocytes produce GM-CSF, LPS and GM-CSF synergize to differentiate monocyte-derived DCs (moDCs) that instruct mDC2s for Th2 cell suppression. Importantly, only allergens with cysteine protease activity trigger GM-CSF production by non-classical monocytes. Hence, the therapeutic effect of LPS is restricted to allergens with this enzymatic activity. Treatment with GM-CSF, however, restores the protective effects of LPS. Thus, GM-CSF produced by non-classical monocytes acts as a rheostat that fine-tunes the pathogenic and therapeutic functions of LPS.

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