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000165135 037__ $$aDZNE-2022-01440
000165135 041__ $$aEnglish
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000165135 1001_ $$aStafford, Che A$$b0
000165135 245__ $$aPhosphorylation of muramyl peptides by NAGK is required for NOD2 activation.
000165135 260__ $$aLondon [u.a.]$$bNature Publ. Group$$c2022
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000165135 520__ $$aBacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan (PGN), a polymeric structure comprising alternating amino sugars that form strands cross-linked by short peptides. Muramyl dipeptide (MDP) has been well documented as a minimal immunogenic component of peptidoglycan1-3. MDP is sensed by the cytosolic nucleotide-binding oligomerization domain-containing protein 24 (NOD2). Upon engagement, it triggers pro-inflammatory gene expression, and this functionality is of critical importance in maintaining a healthy intestinal barrier function5. Here, using a forward genetic screen to identify factors required for MDP detection, we identified N-acetylglucosamine kinase (NAGK) as being essential for the immunostimulatory activity of MDP. NAGK is broadly expressed in immune cells and has previously been described to contribute to the hexosamine biosynthetic salvage pathway6. Mechanistically, NAGK functions upstream of NOD2 by directly phosphorylating the N-acetylmuramic acid moiety of MDP at the hydroxyl group of its C6 position, yielding 6-O-phospho-MDP. NAGK-phosphorylated MDP-but not unmodified MDP-constitutes an agonist for NOD2. Macrophages from mice deficient in NAGK are completely deficient in MDP sensing. These results reveal a link between amino sugar metabolism and innate immunity to bacterial cell walls.
000165135 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
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000165135 650_2 $$2MeSH$$aAcetylmuramyl-Alanyl-Isoglutamine: chemistry
000165135 650_2 $$2MeSH$$aAcetylmuramyl-Alanyl-Isoglutamine: immunology
000165135 650_2 $$2MeSH$$aAcetylmuramyl-Alanyl-Isoglutamine: metabolism
000165135 650_2 $$2MeSH$$aAcetylmuramyl-Alanyl-Isoglutamine: pharmacology
000165135 650_2 $$2MeSH$$aAnimals
000165135 650_2 $$2MeSH$$aBacteria: chemistry
000165135 650_2 $$2MeSH$$aBacteria: immunology
000165135 650_2 $$2MeSH$$aCell Wall: chemistry
000165135 650_2 $$2MeSH$$aHexosamines: biosynthesis
000165135 650_2 $$2MeSH$$aImmunity, Innate
000165135 650_2 $$2MeSH$$aMacrophages: enzymology
000165135 650_2 $$2MeSH$$aMacrophages: immunology
000165135 650_2 $$2MeSH$$aMice
000165135 650_2 $$2MeSH$$aNod2 Signaling Adaptor Protein: agonists
000165135 650_2 $$2MeSH$$aNod2 Signaling Adaptor Protein: metabolism
000165135 650_2 $$2MeSH$$aPeptidoglycan: chemistry
000165135 650_2 $$2MeSH$$aPeptidoglycan: immunology
000165135 650_2 $$2MeSH$$aPhosphorylation
000165135 650_2 $$2MeSH$$aPhosphotransferases (Alcohol Group Acceptor): deficiency
000165135 650_2 $$2MeSH$$aPhosphotransferases (Alcohol Group Acceptor): genetics
000165135 650_2 $$2MeSH$$aPhosphotransferases (Alcohol Group Acceptor): metabolism
000165135 7001_ $$aGassauer, Alicia-Marie$$b1
000165135 7001_ $$ade Oliveira Mann, Carina C$$b2
000165135 7001_ $$00000-0002-4657-9869$$aTanzer, Maria C$$b3
000165135 7001_ $$aFessler, Evelyn$$b4
000165135 7001_ $$0P:(DE-2719)2810988$$aWefers, Benedikt$$b5$$udzne
000165135 7001_ $$aNagl, Dennis$$b6
000165135 7001_ $$aKuut, Gunnar$$b7
000165135 7001_ $$aSulek, Karolina$$b8
000165135 7001_ $$aVasilopoulou, Catherine$$b9
000165135 7001_ $$00000-0002-1747-4144$$aSchwojer, Sophia J$$b10
000165135 7001_ $$00000-0003-2525-6304$$aWiest, Andreas$$b11
000165135 7001_ $$aPfautsch, Marie K$$b12
000165135 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b13$$udzne
000165135 7001_ $$00000-0003-3495-7671$$aYabal, Monica$$b14
000165135 7001_ $$00000-0002-4709-3211$$aFröhlich, Thomas$$b15
000165135 7001_ $$00000-0003-1292-4799$$aMann, Matthias$$b16
000165135 7001_ $$00000-0003-3260-5269$$aGisch, Nicolas$$b17
000165135 7001_ $$00000-0002-3531-1760$$aJae, Lucas T$$b18
000165135 7001_ $$00000-0002-4150-194X$$aHornung, Veit$$b19
000165135 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/s41586-022-05125-x$$gVol. 609, no. 7927, p. 590 - 596$$n7927$$p590 - 596$$tNature <London>$$v609$$x0028-0836$$y2022
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