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Distinct Colitis-Associated Macrophages Drive NOD2-Dependent Bacterial Sensing and Gut Homeostasis

ABSTRACT: In this study, to investigate the role of macrophage GIV in the colon, Katkar et al. employed a myeloid-specific GIV-KO (Ccdc88afl/fl/LysMCre) mouse model to analyze colon transcriptomic data from wild-type (WT) and macrophage-specific GIV-KO mice treated with dextran sulfate sodium (DSS) colitis, with or without muramyl dipeptide (MDP) treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE299285 | GEO | 2025/09/18

REPOSITORIES: GEO

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Impact of NOD2 Genotype on the Innate Monocyte Transcriptome in Crohn’s Disease

Project description:Short title: Innate Gene/miRNA MDP-response in CD RNA-seq and small RNA-seq were used to identify the expression of gene and microRNA (miRNA) in monocytes from healthy controls and patients with Crohn's Disease (CD), with and without NOD2 (nucleotide-binding oligomerization domain-containing protein 2) single nucleotide polymorphisms (SNPs) after stimulation with muramyl dipeptide (MDP).

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NOD2 and desease associated variant NOD2-L1007fsinsC dependent genomewide transcriptional regulation in stable Flp-In HEK cells

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MDP phosphorylation by NAGK is essential for NOD2 activation

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

NOD2 and desease associated variant NOD2-L1007fsinsC dependent genomewide transcriptional regulation in stable Flp-In HEK cells

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

Triggering of NOD2 receptor converts inflammatory Ly6Chigh into Ly6Clow monocytes with patrolling properties.

Project description:In the present study, we demonstrate that NOD2 receptor triggering by muramyl dipeptide converts blood inflammatory Ly6Chigh monocytes into patrolling Ly6Clow monocytes. Muramyl dipeptide administration to Nr4a1-/- mice, which lack Ly6Clow monocytes, and to Ly6Clow-depleted mice leads to the emergence of blood patrolling monocytes expressing phenotypic profile of typical Ly6Clow monocytes, including high expression of CX3CR1 and LFA1. Furthermore using intravital microscopy in live animal models of inflammatory diseases, we observed that converted Ly6Chigh monocytes are capable of patrolling the endothelium of blood vessels and their presence contributes to reduce the inflammatory response following muramyl dipeptide injection.

2019-01-14 | GSE101496 | GEO

Bone marrow derived dendritic cells (BMDC) and MDP and MSU

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2010-12-01 | E-MEXP-2905 | biostudies-arrayexpress

The distinct response of gd T cells to the Nod2 agonist muramyl dipeptide

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scRNAseq of monocytes from Trained immunity experiments

Project description:scRNAseq of monocytes from in vitro Trained immunity experiments stimulated by β-glucan (BG), uric acid (UA), muramyl dipeptide (MDP), oxidized low-density lipoprotein (oxLDL), or RPMI-Control, and respective samples restimulated with Lipopolysaccharide (LPS).

2021-09-30 | E-MTAB-9702 | biostudies-arrayexpress

Expression analysis of human PBMCs stimulated with Borrelia, MDP or Pam3cys.

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2015-06-30 | E-GEOD-68765 | biostudies-arrayexpress

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2025-05-29 | PXD052647 | JPOST Repository

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