Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human macrophages response depends on the infectious agent: is this null hypothesis (H0) an unquestionable dogma?

ABSTRACT: The macrophage is a pluripotent activity in response to infections. We used the central position of this cell type, in an ex vivo system for studying its responses to various infectious agents. Our model is based on cellular macrophages derived from human monocytes purified from healthy individuals. We have stimulated or not the macrophages to obtain paired samples, in a naive environment. Transcriptomic analyzes of match paired and standardized data generated results showing (i) the existence of specific signatures of the infectious agent and its strategy, and (ii) the preponderant existence of macrophage responses specifically related to individuals. The null hypothesis H0, according to which the response of the macrophage is exclusively specific for the pathogen, is refuted. Our results open new perspectives in which the macrophage innate response may be intrinsically associated with the individual.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69964 | GEO | 2016/10/05

SECONDARY ACCESSION(S): PRJNA287277

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The multifaceted responses of human monocytes to IFN-gamma and IL-4 are not reducible to M1/M2 polarization of Macrophages

Project description:Macrophages are known to be polarized into inflammatory (M1) and immunoregulatory (M2) cells when they are stimulated by agonists such as IFN-gamma and IL-4, respectively. If circulating monocytes may be polarized in response to T cell signals is often misguidedly deduced from macrophage results. Here the transcriptional responses of human CD14+ monocytes to IFN-gamma and IL-4 were analyzed using whole genome microarrays. A principal component analysis and hierarchical clustering showed that monocyte and macrophage responses were distinct. Monocytes stimulated with IFN-gamma and IL-4 for 6 hours exhibited some features of macrophage polarization. Indeed, when 80 genes considered as M1 and M2 genes were analyzed, we found that M1 genes were modulated in response to IFN-gamma and that M2 genes were modulated in response to IL-4. The M1 polarization of monocytes was transient because only M2 genes were modulated when monocytes were stimulated with IFN-gamma and IL-4 for 18 hours. However, the activation of monocytes by IFN-gamma and IL-4 could not be reduced to M1/M2 polarization status. Indeed, monocytes exhibited early specific signatures composed of 46 and 39 up-regulated genes in response to IFN-gamma and IL-4, respectively, and a late signature common to both molecules that consisted of 57 up-regulated genes. Taken together, these results demonstrated the extreme plasticity of human monocytes and suggested the existence of a core transcriptional termination program. Using early and late signatures might be pertinent to investigate monocyte activation in inflammatory or infectious diseases. Monocytes were stimulated with IFN-gamma (20ng/mL) or IL-4 (20ng/mL) for 6 and 18 hours or culture for 6 and 18 hours without agonist (Unstimulated samples). Monocytes-derived-macrophages (MDM) stimulated with IFN-gamma and IL-4 for 18 hours were used as controls. Each microarray is derived from a single biological sample.

2013-03-15 | E-GEOD-36537 | biostudies-arrayexpress

Expression data from bone marrow macrophage derived from lean and obese mice after 1,4, and 24h exposition to P.gingivalis

2013-06-12 | GSE47414 | GEO

Histoplasma capsulatum induces a Type I interferon response that contributes to pathogenesis in mice

Project description:To identify signaling pathways that are induced by macrophages infected with Histoplasma capsulatum, we examined the whole genome expression profile of murine bone marrow derived macrophages infected with conidia, the natural infectious particle of Histoplasma. Conidia induced the expression of signature Type I interferon response genes. The induction of a Type I interferon response was specific to conidia, yeast cells did not trigger the response. Macrophages that lack the Type I interferon receptor, IFNAR1, were infected and compared to wild-type macrophages. The expression of some Type I IFN response genes are dependent upon Keywords: Murine bone marrow derived macrophage transcriptional response to infection with Histoplasma capsulatum conidia We analyzed a series of 24 MEEBO arrays on which were hybed RNA amplified from bone marrow derived macrophages from C57BL/6 (WT) or ifnar1-/- mice either mock infected or infected with H. capsulatum conidia or yeast cells.

2010-05-06 | E-GEOD-20022 | biostudies-arrayexpress

Conidia but not yeast cells of the fungal pathogen Histoplasma capsulatum trigger a type I interferon innate immune response in murine macrophages

2010-03-01 | GSE20022 | GEO

Expression data from bone marrow macrophage derived from lean and obese mice after 1,4, and 24h exposition to P.gingivalis

Project description:Obesity is a chronic inflammatory disease that weakens macrophage innate immune response to infections. Since M1 polarization is crucial during acute infectious diseases, we hypothesized that diet-induced obesity inhibits M1 polarization of macrophages in the response to bacterial infection. Using a computational approach in conjunction with microarray data, we identified switching genes that may differentially control the behavior of response pathways in macrophages from lean and obese mice. Bone marrow macrophages (BMMM-NM-&) from lean and obese mice were exposed to live Porphyromonas gingivalis (P. gingivalis) for three incubation times (1 h, 4 h and 24 h). cDNA from BMMM-NM-& of lean and obese mice were hybridized on Affymetrix Mouse Genome 430 2.0 Arrays. Hybridization was performed on three replicates at each time point (18 arrays total).

2013-06-12 | E-GEOD-47414 | biostudies-arrayexpress

Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis

Project description:Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted infections and preventable blindness worldwide. There are, however, limited in vitro models to study the role of host genetics in the response of macrophages to this obligate human pathogen. Here, we describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage-Chlamydia interactions in vitro. We show that iPSdMs support the full infectious life cycle of C. trachomatis in a manner that mimicks the infection of human blood-derived macrophages. Transcriptomic and proteomic profiling of the macrophage response to chlamydial infection highlights the role of the type I interferon and interleukin 10-mediated responses. Using CRISPR/Cas9 technology, we generate biallelic knockout mutations in the host genes encoding IRF5 and IL-10RA in iPSCs, confirming their roles in limiting chlamydial infection in macrophages. This model can potentially be extended to other pathogens and tissue systems to advance our understanding of host-pathogen interactions and the role of human genetics in influencing the outcome of infections.

2018-02-14 | PXD005858 | Pride

Transcription profiling of mouse MH-S cell line with methylglyoxal induces apoptosis and immune response

Project description:Mycobacteria-induced apoptosis of macrophages plays an important role in modulation of the host immune response involving TNF-alpha as major cytokine. The underlying mechanisms are still ill-defined. Here, we show for the first time that methylglyoxal (MG) and AGEs levels were elevated during mycobacterial infection of macrophages and that their increased levels mediated mycobacteria-induced apoptotic and immune response of macrophages. Moreover, we show that high levels of AGEs were formed at the sites of pulmonary tuberculosis. This observation represents the first evidence of the potential involvement of AGEs in tuberculosis and in infectious diseases in general. Global gene expression profiling of MG-treated macrophages reveals diversified potential roles of MG in cellular processes, including apoptosis, immune response, and growth regulation. The results of this study provide new insights into intervention strategies to develop therapeutic tools against infectious diseases in which MG and AGE production plays critical roles. Experiment Overall Design: MH-S cells (ATCC Number: CRL-2019), an alveolar macrophage cell line, was treated with 0.8 mM MG. At different time points after treatment (30 min, 4 h, and 8 h) the cells were harvested for total RNA preparation. As negative control the cells without treatment were included. RNA preparation was performed using Trizol method. Totally three independent experiments were performed, so that each time point consists of biological triplicates.

2008-06-12 | E-GEOD-3837 | biostudies-arrayexpress

Modulation of the TNF-induced macrophage response by synovial fibroblasts

Project description:Here we explored how the human macrophage response to tumor necrosis factor (TNF) is regulated by human synovial fibroblasts, the representative stromal cell type in the synovial lining of joints that become activated during inflammatory arthritis. Genome-wide transcriptome analysis (RNAseq) showed that co-cultured synovial fibroblasts modulate the expression of approximately one third of TNF-inducible genes in macrophages, including expression of target genes in pathways important for macrophage survival and polarization towards an alternatively activated phenotype. This work furthers our understanding of the interplay between innate immune and stromal cells during an inflammatory response, one that is particularly relevant to inflammatory arthritis. Our findings also identify modulation of macrophage phenotype as a new function for synovial fibroblasts that may prove to be a contributing factor in arthritis pathogenesis. Human CD14+ MCSF-differentiated macrophages were cultured with or without synovial fibroblasts in transwell chambers. TNF was added at Day 0, macrophages were harvested at Day 2. Total of 4 samples: (1) macrophages alone (2) macrophages with fibroblasts (3) macrophages with TNF (4) macrophages with fibroblasts and TNF. Macrophage RNA was purified using RNeasy mini kit (Qiagen). Tru-seq sample preparation kits (Illumina) were used to purify poly-A transcripts and generate libraries with multiplexed barcode adaptors. All samples passed quality control on a Bioanalyzer 2100 (Agilent). Paired-end reads (50 x 2 cycles, ~75x106 reads per sample) were obtained on an Illumina HiSeq 2500. The TopHat program was used to align the reads to the UCSC Hg19 human reference genome, while the Cufflinks program allowed for measurements of transcript abundance (represented by Fragments Per Kilobase of exon model per Million mapped reads (FPKM)).

2014-08-04 | E-GEOD-57723 | biostudies-arrayexpress

Macrophage-restricted Interleukin-10 receptor-, but not IL-10 deficiency causes severe spontaneous colitis

Project description:Interleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome wide association studies and experimental animal models point at a central role of the IL-10 axis in Inflammatory Bowel Diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10R?) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1hi-expressingmacrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages, but resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning factor in the colon and define intestinal CX3CR1hi macrophages as a decisive factor that determines gut health or inflammation. Microarray of resident macrophages sorted from colons of Interleukin-10 deficeint mice and macrophage-restricted interleukin-10 receptor deficient mice versus colonic resident macrophages of wild type mice

2014-05-09 | E-GEOD-56444 | biostudies-arrayexpress

EGR1 is a gatekeeper of inflammatory enhancers in human macrophages

Project description:We investigated the function of EGR1 in macrophage differentiation and activation. We generated EGR1 CHIP-seq and CUT-and-RUN data during GM-CSF induced macrophage differentiation, paired with ATAC-seq. We performed RNA-seq and CHIP-seq for H3K27ac in EGR1-depleted differentiated macrophages. Finally we generated RNA-seq data in activated macrophages with EGR1 overexpression.

2020-01-01 | GSE136216 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data