Expression data from human primary monocytes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE55608 | GEO | 2015/03/06
SECONDARY ACCESSION(S): PRJNA240213
REPOSITORIES: GEO
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Project description:A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the antimicrobial mechanism is unclear. Here, we demonstrate that vitamin A mediates host defense through regulation of cellular cholesterol content. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3, the biologically active forms of vitamin A and vitamin D respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Gene expression profiling reveals that ATRA but not 1,25D3 triggers a lipid metabolism and efflux pathway, including expression of lysosomal lipid transport gene NPC2. ATRA-induced decrease in total cellular cholesterol content, subcellular lipid reorganization, lysosomal acidification and antimicrobial activity are all dependent upon expression of NPC2. Finally, the addition of HIV-protease inhibitors known to inhibit cholesterol efflux, Ritonavir and Nelfinavir, blocked both ATRA-induced cholesterol decrease as well as antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated host defense mechanism against M. tuberculosis requires regulation of cellular cholesterol. Monocytes derived from four independent healthy blood donors that were stimulated with control (CTRL), ATRA or 1,25D3 at 10-8M for 18 hours.
2013-12-31 | E-GEOD-46268 | biostudies-arrayexpress
Project description:Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. While most information on these cells comes from in vitro studies in humans or in vivo studies in mice, little is known about monocytes under human disease conditions. We investigated the role of monocytes during sepsis and its resolution in humans. A transcriptomal and functional analysis of blood monocytes from patients during gram negative sepsis and at recovery was performed. Monocytes from sepsis patients showed upregulation of a large number of pro-inflammatory genes and cytokines/chemokines, consistent with an ongoing systemic inflammation. However, these cells showed impairment to ex vivo endotoxin (LPS) challenge, displaying a quantitative decrease in the number of LPS-inducible genes. Moreover, they downregulated the expression of several pro-inflammatory cytokine/chemokine genes, activation marker genes and transcription factors associated with monocyte/macrophage activation, upon ex vivo LPS stimulation. Functionally, they downregulated expression of inflammatory cytokines/chemokines and antigen presentation-related molecules and functions. In contrast, genes and functions related to phagocytosis, anti-microbial activity and tissue remodeling where remained unaffected or even enhanced . Collectively, our observations suggest a genetic and functional re-programming of these cells during human sepsis progression. Understanding the molecular mechanisms which regulate this re-programming will allow to devise strategies which could modulate the response of these cells and hence, disease progression. Blood monocytes from gram-negative sepsis patients during sepsis (Sepsis) and following their recovery (Recovery/Basal) as well as healthy donor (control) were isolated. Thereafter, these cells were treated ex vivo with or without LPS for 3h and analysed for transcriptomic study.
2014-05-14 | E-GEOD-46955 | biostudies-arrayexpress
Project description:The balance between tolerogenic and inflammatory responses determines immune homeostasis in the gut. Dysbiosis and a defective host defense against invading intestinal bacteria can shift this balance via bacterial-derived metabolites and trigger chronic inflammation. We show that the short chain fatty acid butyrate modulates monocyte to macrophage differentiation by promoting antimicrobial effector functions. The presence of butyrate modulates antimicrobial activity via a shift in macrophage metabolism and reduction in mTOR activity. This mechanism is furthermore dependent on the inhibitory function of butyrate on histone deacetylase 3 (HDAC3) driving transcription of a set of antimicrobial peptides including calprotectin. The increased antimicrobial activity against several bacterial species is not associated with increased production of conventional cytokines. Butyrate imprints antimicrobial activity of intestinal macrophages in vivo. Our data suggest that commensal bacteria derived butyrate stabilize gut homeostasis by promoting antimicrobial host defense pathways in monocytes that differentiate into intestinal macrophages.
2019-01-30 | GSE111049 | GEO
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
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. Total RNA obtained from human monocyte exposure treated with LPS for 3h, 6h, or 24h, subsequent to endotoxin tolerization or not.
2009-03-13 | E-GEOD-15219 | biostudies-arrayexpress
Project description:Blood monocytes serve as the first line of host defense and are equipped to recognize and respond to infection by triggering an immune-inflammatory response. While most information on these cells comes from in vitro studies in humans or in vivo studies in mice, little is known about monocytes under human disease conditions. We investigated the role of monocytes during sepsis and its resolution in humans. A transcriptomal and functional analysis of blood monocytes from patients during gram negative sepsis and at recovery was performed. Monocytes from sepsis patients showed upregulation of a large number of pro-inflammatory genes and cytokines/chemokines, consistent with an ongoing systemic inflammation. However, these cells showed impairment to ex vivo endotoxin (LPS) challenge, displaying a quantitative decrease in the number of LPS-inducible genes. Moreover, they downregulated the expression of several pro-inflammatory cytokine/chemokine genes, activation marker genes and transcription factors associated with monocyte/macrophage activation, upon ex vivo LPS stimulation. Functionally, they downregulated expression of inflammatory cytokines/chemokines and antigen presentation-related molecules and functions. In contrast, genes and functions related to phagocytosis, anti-microbial activity and tissue remodeling where remained unaffected or even enhanced . Collectively, our observations suggest a genetic and functional re-programming of these cells during human sepsis progression. Understanding the molecular mechanisms which regulate this re-programming will allow to devise strategies which could modulate the response of these cells and hence, disease progression.
2014-05-14 | GSE46955 | GEO
Project description:A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the antimicrobial mechanism is unclear. Here, we demonstrate that vitamin A mediates host defense through regulation of cellular cholesterol content. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3, the biologically active forms of vitamin A and vitamin D respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Gene expression profiling reveals that ATRA but not 1,25D3 triggers a lipid metabolism and efflux pathway, including expression of lysosomal lipid transport gene NPC2. ATRA-induced decrease in total cellular cholesterol content, subcellular lipid reorganization, lysosomal acidification and antimicrobial activity are all dependent upon expression of NPC2. Finally, the addition of HIV-protease inhibitors known to inhibit cholesterol efflux, Ritonavir and Nelfinavir, blocked both ATRA-induced cholesterol decrease as well as antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated host defense mechanism against M. tuberculosis requires regulation of cellular cholesterol.
2013-12-31 | GSE46268 | GEO
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
Project description:INTRODUCTION: Persistent lung inflammation, with an influx of polymorphonuclear leukocytes and monocytes, occurs early in bronchopulmonary dysplasia. We hypothesized that: 1) that interleukin-10, a potent anti-inflammatory cytokine, would cause a markedly different gene expression profile compared to dexamethasone in these cells, and 2) monocyte insensitivity to dexamethasone was related to glucocorticoid receptor expression. RESULTS: For polymorphonuclear leukocytes, there were <20% of genes changing expression in common between interleukin-10 and dexamethasone. The monocyte had 5 times the number of genes changing expression with interleukin-10 compared to the polymorphonuclear leukocyte. Dexamethasone, in the therapeutic range, had no effect on gene expression in monocytes. The order of potency for inhibition of interleukin-8 release from monocytes was IL-10>betamethasone>> dexamethasone and hydrocortisone. Glucocorticoid potency was directly related to the degree of glucocorticoid receptor translocation to the monocyte nucleus. DISCUSSION: Gene expression profiles by IL-10 versus dexamethasone indicates that there may be major differences in efficacy and adverse effects if interleukin-10 is used for therapy in the future. Betamethasone may be a better therapeutic choice than dexamethasone. METHODS: Isolated cord blood cells were pre-incubated with anti-inflammatory agents prior to endotoxin stimulation. Measurements were made by microarrays, RT-qPCR, ELISA, and Western blots. Isolation of cord blood polymorphonuclear leukocytes and monocytes separately from 5 subjects. Endotoxin stimulation in cell culture for 4 hours. Comparison of gene expression between endotoxin alone versus endotoxin-stimualted cells pretreated with interleukin-10 or dexamethasone (at equimolar, therapeutic levels, 10-8 M. Cell Types : MONOs, PMNs; Treatments: LPS, LPS+IL-10, LPS+DEX
2012-02-16 | E-GEOD-35683 | biostudies-arrayexpress
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