Transcriptional profiling of macrophage plasticity following recovery from Lipopolysaccharide (LPS) tolerance
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47783 | GEO | 2013/12/06
SECONDARY ACCESSION(S): PRJNA207802
REPOSITORIES: GEO
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Project description:To investigate the plasticity of Lipolysaccharide (LPS) tolerance, we employed microarray profiling to analyse the gene expression profile in macrophage. Four macrophage populations were induced; Untreated macrophages (Control group), Acute response to LPS (LPS activation group), LPS tolerance (T – Tolerant group) and recovered (R = recovered macrophage group) Using transcriptional analysis we demonstrate that recovery from LPS tolerance (R – Recovery), as defined by cytokine gene expression, is associated with a global change in the transcriptional profile of macrophage. This data confirms that LPS tolerance is a transient state which results in induction of novel hybrid macrophage activation state with a unique transcriptional signature. Bone marrow derived macrophages were polarised into three activation states; Acute response to LPS (A), LPS tolerant (T) and recovered (R). Gene expression was measured at 4 hours post stimulation with LPS. Three independent experiments were performed to measure gene expression changes between each macrophage group.
2013-12-06 | E-GEOD-47783 | biostudies-arrayexpress
Project description:Transcriptional profiling of macrophage plasticity following recovery from Lipopolysaccharide (LPS) tolerance
| PRJNA207802 | ENA
Project description:Among the multiple mechanisms that control the intensity and duration of macrophage activation, the development of a state of refractoriness to a second stimulation in cells treated with LPS has long been recognized. Release of inhibitory cytokines and alterations in intracellular signaling pathways may be involved in the development of LPS tolerance. Although a number of molecules have been implicated, a detailed picture of the molecular changes in LPS tolerance is still missing. We have used a genome-wide gene expression analysis approach to (i) define which fraction of LPS target genes are subject to tolerance induction and (ii) identify genes that are expressed at high levels in tolerant macrophages. Our data show that in LPS tolerant macrophages the vast majority of LPS-induced gene expression is abrogated. The extent of tolerance induction varies for individual genes, and a small subset appears to be excepted. Compared to other negative control mechanisms of macrophages, e.g. IL-10-induced deactivation, LPS-tolerance inhibits a much wider range of transcriptional targets. Some previously described negative regulators of TLR-signaling (e.g. IRAK-M) were confirmed as expressed at higher levels in LPS-tolerant macrophages. In addition, we discuss other potential players in LPS tolerance identified in this group of genes. Keywords: pre and restimulation with LPS, tolerance induction
2007-08-10 | GSE8621 | GEO
Project description:Among the multiple mechanisms that control the intensity and duration of macrophage activation, the development of a state of refractoriness to a second stimulation in cells treated with LPS has long been recognized. Release of inhibitory cytokines and alterations in intracellular signaling pathways may be involved in the development of LPS tolerance. Although a number of molecules have been implicated, a detailed picture of the molecular changes in LPS tolerance is still missing. We have used a genome-wide gene expression analysis approach to (i) define which fraction of LPS target genes are subject to tolerance induction and (ii) identify genes that are expressed at high levels in tolerant macrophages. Our data show that in LPS tolerant macrophages the vast majority of LPS-induced gene expression is abrogated. The extent of tolerance induction varies for individual genes, and a small subset appears to be excepted. Compared to other negative control mechanisms of macrophages, e.g. IL-10-induced deactivation, LPS-tolerance inhibits a much wider range of transcriptional targets. Some previously described negative regulators of TLR-signaling (e.g. IRAK-M) were confirmed as expressed at higher levels in LPS-tolerant macrophages. In addition, we discuss other potential players in LPS tolerance identified in this group of genes. Experiment Overall Design: Cells were either prestimulated (1_X) or not (0_X) for 18h with 100 ng/ml LPS. Media was exchanged and after 2h rest, cells either restimulated (X_1) or not (X_0) with again 100 ng/ml LPS. This resulted in 4 experimental conditions: 0_0, 0_1, 1_0 and 1_1. There were 3 biological replicates done, resulting in 12 arrays altogether.
2008-06-16 | E-GEOD-8621 | biostudies-arrayexpress
Project description:Monocytes and macrophages are central to host defense but also contribute to inflammation-associated pathology. Efforts to manipulate monocyte and macrophage function are limited by our ability to effectively quantify the functional programs of these cells. We identified the gene Fth1, which encodes the Ferritin heavy chain, as highly predictive of alveolar macrophage transcriptomic states during LPS-induced lung inflammation and developed a novel Fth1-mScarlet reporter mouse. In the steady state lung, high Fth1-mScarlet expression is restricted to alveolar macrophages. In response to LPS-induced lung inflammation, Fth1 reporter activity is robustly increased in monocytes, with its expression reporting genes that are differentially expressed in monocytes versus macrophages. Consistent with this reporter associated gene profile, within the Lyz2-GFP+CD11b+Ly6C+ gate the highest Fth1 reporter expression was observed CD11c+ cells, indicative of monocyte-to-macrophage differentiation. While Fth1-mScarlet was induced in monocytes responding to either TLR4 ligation or M-CSF induced macrophage differentiation in vitro, TLR4-dependent expression occurred with greater speed and magnitude. Considering this, we suggest that Fth1-mScarlet expression reports monocyte-to-macrophage differentiation, with increased expression in pro-inflammatory states. Dissecting macrophage differentiation from inflammatory programs will be enhanced when combining Fth1-mScarlet with other reporter systems. Thus, the Fth1-mScarlet model addresses an important lack of tools to report the diverse spectrum of monocyte and macrophage states in vivo.
2024-09-25 | GSE278058 | GEO
Project description:Analysis of gene expression in explanted peritoneal macrophages from Aoah -/- and Aoah +/+ mice treated with LPS 21 days prior to harvest. Explanted peritoneal machrophages were challenged with LPS or control (PBS). The study seeks to characterize global gene expression in the state of prolonged LPS tolerance induced in mice lacking the LPS-inactivating enzyme Aoah. Groups of 9 C57BL/6 Aoah+/+ or Aoah-/- mice were given i.p. injections of 10 µg E. coli LPS/mouse. Twenty-one days later (when Aoah-/- mice remain tolerant and Aoah+/+ mice have recovered), peritoneal macrophages were harvested and the yields from three mice were pooled to form 3 samples per group (i.e., three samples of Aoah+/+ and Aoah-/- mice, with each sample comprised of peritoneal macrophages from 3 mice). Next day, cells were challenged with LPS or PBS and whole RNA was isolated 2 hours later and used for microarray experiments.
2012-08-17 | E-GEOD-40154 | biostudies-arrayexpress
Project description:We sought to characterize pulmonary interstitial macrophage (IM) origin, subsets, and transcriptomic profiles during homeostasis and lipopolysaccharide (LPS) induced acute lung inflammation. During homeostasis, we used three complementary methods: spectral flow cytometry, single-cell RNA-sequencing, and gene regulatory network enrichment to demonstrate that IMs can be divided into two core subsets distinguished by surface and transcriptional expression of folate receptor β (Folr2/FRβ). Within FRβ+ IMs we identified a subpopulation marked by co-expression of LYVE1. During acute LPS-induced inflammation, lung IM numbers expand. Lineage tracing revealed IM expansion was due to recruitment of monocyte-derived IMs. At the peak of inflammation, recruited IMs were comprised of two unique subsets defined by expression of genes associated with interferon signaling and glycolytic pathways. As recruited IMs matured, they adopted the overall transcriptional state of FRβ- resident IMs but retained expression in several origin-specific genes. FRβ+ IMs were of near-pure resident origin.
2023-03-17 | GSE218884 | GEO
Project description:Recovery of cardiac function is the ultimate goal of heart failure therapy yet is infrequently observed and remains poorly understood. Here we characterize the cellular landscape and predictors of cardiac recovery by performing single nucleus RNA-sequencing (snRNA-seq) from 40 heart failure patients who recovered LV systolic function following left ventricular assist device (LVAD) implantation and patients who did not recover and non-diseased donors. We identify cell type specific transcriptional signatures of recovery in all cell types, most prominently in macrophages and fibroblasts. Pro-inflammatory macrophages and inflammatory signalling in fibroblasts were negative predictors of recovery, while downregulation of RUNX1 transcriptional activity in macrophages and fibroblasts was associated with recovery. In silico perturbation of RUNX1 in macrophages and fibroblasts recapitulated the transcriptional state of recovery. In a mouse model of cardiac recovery mediated by BRD4 inhibition, we observed a decrease in macrophage and fibroblast Runx1 expression, diminished chromatin accessibility within a Runx1 intronic peak, and acquisition of human recovery signatures. These findings suggest that cardiac recovery is a unique biological state and identify RUNX1 as a possible therapeutic target to facilitate cardiac recovery.
2023-02-28 | GSE226314 | GEO
Project description:We performed gene expression microarray experiments to compare the global transcriptional response induced by b-glucans and LPS with their secretomes. We identified 1683, 767 and 1447 genes with over two-fold increase or decrease in LPS-, curdlan- or GBY-stimulated macrophages, respectively. We show that both LPS and b-glucan induces significant gene expression changes in macrophages, but only b-glucans activate a robust protein secretion. The gene expression of human primary macrophage cells was measured at 6 hours after exposure the cells to 1 M-BM-5g LPS or 10 M-BM-5g Curdlan or 100 M-BM-5g GBY (glucan from bakerM-BM-4s yeast), also 0-group was included. Three independent experiments were performed using three different donors for each experiment.
2014-05-15 | E-GEOD-32282 | biostudies-arrayexpress
Project description:Macrophage plasticity allows cells to adopt different phenotypes, a property with potentially important implications in chronic pulmonary disorders such as cystic fibrosis (CF). We examined the transcriptional and functional significance of macrophage repolarization from an “M1” (LPS-stimulated) towards an “M2” phenotype using 5 stimuli. We found that macrophages exhibit highly diverse responses to distinct M2-polarizing stimuli. Specifically, we observed that IL-10 abrogated LPS-tolerance allowing for rapid restoration of LPS responsiveness. In contrast, IL-4 enhanced LPS-tolerance, dampening pro-inflammatory responses after repeat LPS challenge. We found enrichment of phagocytosis-associated pathways in macrophages stimulated with IL-10, leading them to display the greatest efferocytosis ability. Finally, we observed that CF macrophages had intact reparative responses, suggesting that macrophage contributions to CF lung disease are shaped by their environmental milieu and are modifiable. These findings highlight the diversity of macrophage activation states, attribute functional consequences to these stimuli, and provide a unique resource of human macrophage repolarization markers.
2018-09-30 | GSE100521 | GEO