Human dendritic cell microRNA profile after NOD2 and / or TLR2 stimulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE44785 | GEO | 2013/06/01
SECONDARY ACCESSION(S): PRJNA191800
REPOSITORIES: GEO
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Project description:microRNA expression in human monocyte-derived DCs following stimulation with NOD2 ligand MDP, TLR2 ligand Pam3CSK4, or both. 4 condition experiment with two timepoints, and 4 biological replicates. Conditions: unstimulated; MDP stimulated; Pam3CSK4 stimulated; MDP + Pam3CSK4 stimulated. Timepoints: 4 hours and 24 hours.
2013-06-01 | E-GEOD-44785 | biostudies-arrayexpress
Project description:Most of the genes were self-tolerized by Pam3CSK4 and MDP but there was no or minimal cross-tolerization. The transcriptome induced via Nod2 stimulation is greatly expanded in TLR2-tolerant macrophages. Keywords: self and cross tolerance by MDP or Pam3CSK4
2008-03-15 | GSE10182 | GEO
Project description:Most of the genes were self-tolerized by Pam3CSK4 and MDP but there was no or minimal cross-tolerization. The transcriptome induced via Nod2 stimulation is greatly expanded in TLR2-tolerant macrophages. Experiment Overall Design: Genes induced by Pam3CSK4 or MDP were selected based on a three-fold increase over expression levels in unstimulated macrophages. Tolerized genes are defined as genes downregulated more than 2-fold in tolerant macrophages stimulated with Pam3CSK4 or MDP.
2008-04-05 | E-GEOD-10182 | biostudies-arrayexpress
Project description:Recognition and response to gram-positive bacteria by macrophages and dendritic cells is mediated in part through TLR2. We found that that Streptococcus pneumoniae cell wall fragments, containing primarily peptidoglycan and teichoic acids, induced prodigious secretion of IL-10 from macrophages and dendritic cells and was dependent on TLR2 and NOD2, a cytoplasmic CARD-NACHT-LRR protein encoded by Card15. IL-10 secretion in response to cell walls was also dependent on RICK/RIP2, a kinase associated with NOD2, and MYD88 but independent of the ERK/p38 pathway. The reduction of IL-10 secretion by cell wall-activated NOD2-deficient myeloid–derived cells translated into downstream effects on IL-10 target gene expression and elevations in subsets of pro-inflammatory cytokine expression normally restrained by autocrine/paracrine effects of IL-10. Since NOD2 is linked to aberrant immune responses in Crohn’s Disease patients bearing mutations in CARD15, the temporal and quantitative effects of the TLR2/NOD/RICK pathway on IL-10 secretion may affect homeostatic control of immune responses to gram-positive bacteria. Keywords: immune response simulated pathogen response
2008-09-01 | GSE8960 | GEO
Project description:Bacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan, a polymeric structure comprising of alternating amino sugars. Muramyl dipeptide (MDP) is the minimal, biologically active molecular structure derived from peptidoglycan, and its immunogenicity is well documented in numerous studies. MDP is sensed by the cytosolic nucleotide-binding and nucleotide oligomerization domain-like receptor 2 (NOD2), which triggers a pro-inflammatory response upon engagement 1,2. Conducting a forward genetic screen to identify factors required for MDP detection, we discovered that N-acetylglucosamine kinase (NAGK) is essential for the immunostimulatory activity of MDP. NAGK, which has previously been identified to contribute to the hexosamine salvage pathway in humans, is broadly expressed and inducible in innate immune cells. Mechanistically, NAGK functions upstream of NOD2 in that it directly phosphorylates the N-acetylmuramic moiety of MDP at the hydroxyl group of its C6 position, yielding 6-O-phospho-MDP. NAGK-phosphorylated MDP constitutes an essential component of NOD2 dependent signal transduction. Altogether, these results unveil a previously unknown interconnection of amino sugar metabolism and innate immunity to bacterial cell walls.
2022-06-13 | PXD022384 | Pride
Project description:NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP) and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs e.g. Crohn disease, asthma and atopic eczema. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. The exact transcriptomal signatures that define the cellular programs downstream of NOD2 activation and the influence of the Crohn-associated variant L1007fsinsC are yet to be defined. To describe the MDP-induced activation program, we analyzed the transcriptomal reactions of isogenic HEK293 cells expressing NOD2wt or NOD2L1007fsinsC to stimulation with MDP. Importantly, a clear loss-of-function could be observed in the cells carrying the Crohn-associated variant L1007fsinsC, while the NOD2wt cells showed differential regulation of growth factors, chemokines and several antagonists of NF-κB, e.g. TNFAIP3 (A20) and IER3. To elucidate the MDP-induced activation program we generated isogenic HEK293 cells stably expressing wildtype NOD2 or NOD2L1007fsinsC using a FRT-recombinase based approach. Cells carrying the inserted vector cassette were used as controls (mock-transfectant). To comprehensively analyze NOD2-mediated innate immune responses we analyzed transcriptomal signature patterns using genome-wide cDNA microarrays. Samples were harvested from cell cultures under normal growth conditions 0 h, 2 h and 6 h after MDP‑ stimulation of the cells.
2013-01-01 | E-GEOD-22611 | biostudies-arrayexpress
Project description:NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP) and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs e.g. Crohn disease, asthma and atopic eczema. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. The exact transcriptomal signatures that define the cellular programs downstream of NOD2 activation and the influence of the Crohn-associated variant L1007fsinsC are yet to be defined. To describe the MDP-induced activation program, we analyzed the transcriptomal reactions of isogenic HEK293 cells expressing NOD2wt or NOD2L1007fsinsC to stimulation with MDP. Importantly, a clear loss-of-function could be observed in the cells carrying the Crohn-associated variant L1007fsinsC, while the NOD2wt cells showed differential regulation of growth factors, chemokines and several antagonists of NF-κB, e.g. TNFAIP3 (A20) and IER3.
2013-01-01 | GSE22611 | GEO
Project description:Recognition and response to gram-positive bacteria by macrophages and dendritic cells is mediated in part through TLR2. We found that that Streptococcus pneumoniae cell wall fragments, containing primarily peptidoglycan and teichoic acids, induced prodigious secretion of IL-10 from macrophages and dendritic cells and was dependent on TLR2 and NOD2, a cytoplasmic CARD-NACHT-LRR protein encoded by Card15. IL-10 secretion in response to cell walls was also dependent on RICK/RIP2, a kinase associated with NOD2, and MYD88 but independent of the ERK/p38 pathway. The reduction of IL-10 secretion by cell wall-activated NOD2-deficient myeloidâderived cells translated into downstream effects on IL-10 target gene expression and elevations in subsets of pro-inflammatory cytokine expression normally restrained by autocrine/paracrine effects of IL-10. Since NOD2 is linked to aberrant immune responses in Crohnâs Disease patients bearing mutations in CARD15, the temporal and quantitative effects of the TLR2/NOD/RICK pathway on IL-10 secretion may affect homeostatic control of immune responses to gram-positive bacteria. Experiment Overall Design: KO mice were treated with a cel wall extract and evaluated for immune response 1 hr and 4 hrs after treatment
2008-10-25 | E-GEOD-8960 | biostudies-arrayexpress
Project description:We have begun to approach gd T cells more as prospective innate cells than as conventional T cells. Recent results indicated that purified gd T cells are primed directly in response to pathogen associated molecular patterns (PAMPs) to better respond to secondary signals and increase expression of chemokine and activation-related genes. In microarray and real time PCR analyses of RNA derived from bovine and human gd T cells, transcripts encoding Nod2 were repeatedly amplified. Nod2 is the intracellular receptor for muramyl dipeptide (MDP), a subunit of PGN, functions in regulating innate activities, and was thought to be expressed primarily in APCs. Given our repeated detection of Nod2 transcripts in gd T cells, the specific direct response of gd T cells to MDP was analyzed by microarray, real time PCR, proteome array and in a functional priming assay. The results indicate a subtle activation in response to MDP akin to priming, and suggest a unique mechanism for differential gene expression. Keywords: Comparison of genes expressed after stimulation of bovine gd T cells with either PBS or MDP
2009-02-10 | GSE6918 | GEO
Project description:Toll-like receptor 2 (TLR2) is a pattern recognition receptor that, upon ligation by microbial molecules, interacts with other proteins to initiate pro-inflammatory responses by the cell. Statins (hydroxymethylglutaryl coenzyme A reductase inhibitors), drugs widely prescribed to reduce hypercholesterolemia, are reported to have both pro- and anti-inflammatory effects upon cells. Some of these responses are presumed to be driven by effects on signaling proteins at the plasma membrane, but the underlying mechanisms remain obscure. We reasoned that profiling the effect of statins on the repertoire of TLR2-interacting proteins might provide novel insights into the mechanisms by which statins impact inflammation. In order to study the TLR2 interactome, we designed a co-immunoprecipitation (IP)-based cross-linking proteomics study. A hemagglutinin (HA)-tagged-TLR2 transfected HEK293 cell line was utilized to precipitate the TLR2 interactome upon cell exposure to the TLR2 agonist Pam3CSK4 and simvastatin, singly and in combination. To stabilize protein interactors, we utilized two different chemical cross-linkers with different spacer chain lengths. Proteomic analysis revealed important combinatorial effects of simvastatin and Pam3CSK4 on the TLR2 interactome. After stringent data filtering, we identified alpha-centractin (ACTR1A), an actin-related protein and subunit of the dynactin complex, as a potential interactor of TLR2. The interaction was validated using biochemical methods. RNA interference studies revealed an important role for ACTR1A in induction of pro-inflammatory cytokines. Taken together, we report that statins remodel the TLR2 interactome, and we identify ACTR1A, a part of the dynactin complex, as a novel regulator of TLR2-mediated immune signaling pathways.
2019-06-24 | PXD012759 | Pride