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MDP- and Pam3CSK4-induced genes in naïve and tolerant macrophages

ABSTRACT: 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

ORGANISM(S): Mus musculus

PROVIDER: GSE10182 | GEO | 2008/03/15

SECONDARY ACCESSION(S): PRJNA108395

REPOSITORIES: GEO

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Transcription profiling of mouse naive and tolerant macrophages treated with MDP- and Pam3CSK4

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

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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.

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Transcriptome response after addition of individual agonists of TLR4 (MPLA) and NOD2 (MDP) receptors to THP-1 cells or its combination

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Project description:Aim of this project was to examine the global gene expression profiles of mononuclear phagocytes recruited from peripheral blood to the alveolar space following alveolar deposition of the TLR2-ligand Pam3CSK4 in transgenic CX3CR1+/GFP mice.

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Peptidoglycan metabolite photoaffinity reporters reveal direct binding to intracellular pattern recognition receptors and Arf GTPases

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2020-05-26 | PXD012350 | Pride

MF59 and Pam3CSK4 boost adaptive responses to influenza subunit vaccine through an IFN type I independent mechanism of action

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