Expression data from peritoneal macrophages stimulated with trehalose-6,6'-dimycolate (TDM)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE52338 | GEO | 2013/11/14
SECONDARY ACCESSION(S): PRJNA227446
REPOSITORIES: GEO
Similar Datasets
Project description:Macrophage-inducible C-type lectin (Mincle, Clec4e) is a pathogen sensor that recognizes pathogenic fungi and Mycobactrium tuberculosis. We perfomed microarray analysis using peritoneal macrophages stimulated with TDM, a mycobacterial cell wall glycolipid that is known to be a Mincle ligand. Many chemokine and cytokine genes were upregulated in wildtype macrophages stimulated with TDM. Upregulation of these genes were completely abolishd in Mincle KO macrophages. Peritoneal macrophages from WT and Mincle KO mice were stimulated with TDM or vehicle for 24 h (3 samples each). Microarray analysis was performed using Affymetrix Mouse 430 2.0.
2013-11-14 | E-GEOD-52338 | biostudies-arrayexpress
Project description:Sensing of Mycobacterium tuberculosis by the immune system relies on recognition by macrophages. Mycobacterial cord factor, trehalose-6,6’-dimycolate (TDM), is the most abundant cell wall glycolipid and binds to the C-type lectin receptor Mincle. To explore the kinase signaling linking the TDM-Mincle interaction to gene expression, we employed quantitative phosphoproteome analysis using dimethyl-labeling and high-resolution mass spectrometry. TDM caused upregulation of 6.7% and suppressed 3.8% of the 14k phospho-sites identified in 3727 proteins. Mincle-dependent phosphorylation was observed for several canonical players of CLR signaling (e.g. PLC, PKC), and was enriched for PKC and GSK3 kinase motifs. Mincle-dependent activation of the PI3K-AKT-GSK3 pathway contributed to TDM-induced inflammatory gene expression and required the PI3K regulatory subunit p85. Unexpectedly, a substantial fraction of TDM-induced phosphorylation was Mincle-independent, a finding which was paralleled by RNAseq-based transcriptome data. GO and pathway enrichment analysis of both datasets concurred in the requirement for Mincle in “innate immune response”. In contrast, Mincle-independent phosphorylation and transcriptome responses to TDM were linked to “cell cycle” and to the DNA damage response. Collectively, our global analyses show substantial reprogramming of macrophages by mycobacterial cord factor and reveal a dichotomy of Mincle-dependent and –independent signaling linked to distinct biological responses
2019-01-17 | PXD009513 | Pride
Project description:Immune sensing of Mycobacterium tuberculosis relies on recognition by macrophages. Mycobacterial cord factor, trehalose-6,6’-dimycolate (TDM), is the most abundant cell wall glycolipid and binds to the C-type lectin receptor (CLR) MINCLE. To explore the kinase signaling linking the TDM-MINCLE interaction to gene expression, we employed quantitative phosphoproteome analysis. TDM caused upregulation of 6.7% and suppressed 3.8% of the 14,000 phospho-sites identified on 3727 proteins. MINCLE-dependent phosphorylation was observed for canonical players of CLR signaling (e.g. PLCg, PKCd), and was enriched for PKCd and GSK3 kinase motifs. MINCLE-dependent activation of the PI3K-AKT-GSK3 pathway contributed to inflammatory gene expression and required the PI3K regulatory subunit p85a. Unexpectedly, a substantial fraction of TDM-induced phosphorylation was MINCLE-independent, a finding paralleled by transcriptome data. Bioinformatic analysis of both datasets concurred in the requirement for MINCLE for innate immune response pathways and processes. In contrast, MINCLE-independent phosphorylation and transcriptome responses were linked to cell cycle regulation. Collectively, our global analyses show substantial reprogramming of macrophages by TDM and reveal a dichotomy of MINCLE-dependent and -independent signaling linked to distinct biological responses.
2019-06-01 | GSE115322 | GEO
Project description:Analysis of total RNAs from wild-type and Mincle-KO macrophages stimulated with TLR2 ligand and co-stimulated with TLR2 ligand and Mincle ligand. And analysis of total and polysomal RNAs from wild-type macrophages co-stimulated with TLR2 ligand and Mincle ligand in the presence or absence of DHS inhibitor (GC7). Mincle is a C-type lectin receptor for trehalose dimycolate, a mycobacterial cell wall component. And results provide insight into the crosstalk between the TLR2 and Mincle signaling pathways by RNA-seq assay and identifying potential targets of Mincle-mediated translational control by polysome profiling assay.
2016-07-10 | GSE70793 | GEO
Project description:Mycobacteria can survive and persist in macrophages despite triggering multiple pattern recognition receptors and strong T cell-derived IFN-gamma production. The mycobacterial cord factor trehalose-6,6-dimycolate binds the C-type lectin receptor Mincle and induces inflammatory gene expression through the Syk-Card9 pathway. It is well established that TDM and IFN-gamma synergize to induce expression of iNOS. However, the cord factor may also act to down-regulate IFN-gamma-induced responses and contribute to mycobacterial immune evasion. Here, we have investigated the cross-regulation of the macrophage transcriptome by IFN-gamma and by TDM, as well as its synthetic analog TDB. For genome-wide expression profiling, bone marrow derived macrophages (BMMs) from female C57BL/6 mice aged 6 to 8 weeks were used for stimulation.
2019-09-10 | GSE137150 | GEO
Project description:Pathogenic mycobacteria subvert immune responses to survive and replicate in macrophages. Mycobacterial cell wall components are sensed by several C-type lectin receptors, including MINCLE, the receptor for the cord factor trehalose-6,6-dimycolate (TDM). Regulation of innate immune cells relies on miRNAs, some of which are induced by mycobacterial ligands. Thus, MTB may exploit host miRNAs to establish its niche in macrophages. Here, we have employed conditional knockout mice for the microprocessor component DGCR8 to investigate the impact of miRNAs on the macrophage response to the mycobacterial cord factor. Deletion of DGCR8 during differentiation of macrophages from bone marrow progenitors significantly reduced the cell yield, but did not interfere with macrophage differentiation as determined by typical surface marker expression and phagocytic capacity. DGCR8-deficient macrophages expressed reduced levels of constitutive and TDM-inducible miRNAs, yet in turn accumulated primary miRNA transcripts. RNAseq revealed a modest type I interferon (IFN) signature in resting DGCR8-deficient macrophages. Stimulation of DGCR8-deficient macrophages with TDM induced overshooting and prolonged expression of interferon response genes, which was associated with enhanced expression of IFNb and could be largely prevented by antibodies to type I interferon. In turn, exogenous IFNb upregulated CXCL10 and CD69 to similar levels in control and DGCR8-deficient macrophages, indicating that signaling downstream of the type I IFN receptor was unaltered. Infection with live Mycobacterium bovis Bacille Calmette-Guerin (BCG) replicated the enhanced interferon response of DGCR8-deficient macrophages. Together, our results reveal an essential role for DGCR8 in curbing IFNb expression and IFN-dependent macrophage activation by mycobacteria.
2020-04-28 | GSE149441 | GEO
Project description:Bone marrow derived macrophages from wt and card9 KO mice were stimulated with CpG, Curdlan or TDB, an analogon to the mycobacterial cord factor TDM for 48h, respectively. Keywords: card9 knockout, macropphage, TDB wt or card9 KO macrophages stimulated for 48h
2009-01-31 | E-GEOD-10530 | biostudies-arrayexpress
Project description:Bone marrow derived macrophages from wt and card9 KO mice were stimulated with CpG, Curdlan or TDB, an analogon to the mycobacterial cord factor TDM for 48h, respectively. Keywords: card9 knockout, macropphage, TDB
2009-02-01 | GSE10530 | GEO
Project description:Macrophage-inducible C-type lectin (Mincle) dependent sensing of pathogens trig-gers proinflammatory immune responses in professional phagocytes that contribute to protect the host against pathogen invasion. Here, we examined whether overex-pression of Mincle designed to improve early pathogen sensing by professional phagocytes would improve lung protective immunity against Streptococcus pneu-moniae in mice. Proteomic profiling of alveolar macrophages (AM) of Mincle trans-genic (tg) mice stimulated with the Mincle-specific pneumococcal ligand glucosyl-diacylglycerol (Glc-DAG) revealed increased Nlrp3 inflammasome activation and downstream IL-1 cytokine release that was not observed in Glc-DAG stimulated Mincle KO or Nlrp3 KO macrophages. Along this line, Mincle tg mice also responded with a stronger Nlrp3 expression and early proinflammatory cytokine release after challenge with S. pneumoniae, ultimately leading to fatal pneumonia in the Mincle tg mice. Importantly, Nlrp3 inhibitor treatment of Mincle tg mice significantly mitigated the observed hyperinflammatory response to pneumococcal challenge. Together, we show that overexpression of the pattern recognition receptor Mincle triggers in-creased Glc-DAG dependent Nlrp3 inflammasome activation in professional phago-cytes leading to fatal pneumococcal pneumonia in mice, which is amenable to Nlrp3 inhibitor treatment. These data show that ectopic expression of Mincle receptor con-fers increased susceptibility rather than resistance to S. pneumoniae in mice, thus highlighting the importance of an inducible Mincle receptor expression in response to microbial challenge.
2020-10-05 | PXD018752 | Pride
Project description:Helicobacter pylori (H. pylori) causes assorted gastrointestinal disorders. H. pylori-specific T cells develop during infection, which is a prerequisite for the induction of gastritis and malignancy. How the innate immune system senses H. pylori to prime T cells remains unclear. We report that cholesteryl glucosides in H. pylori activate innate immunity through C-type lectin receptors (CLRs). Cholesteryl acyl α-glucoside (αCAG) was identified as a ligand for Mincle (Clec4e). Upon H. pylori infection, T cell responses and gastritis were ameliorated in Mincle-deficient mice, although bacterial numbers were comparable.Thus the cholesteryl lipid–CLR axis exacerbates H. pylori-induced gastric inflammation with limited contribution to protective immunity.
2020-09-19 | GSE136203 | GEO