Chen Shuyuan, Putnik Rachel, Li Xi, Diwaker Alka, Vasconcelos Marina, Liu Shuzhen, Gondi Sudershan, Zhou Junhui, Guo Lei, Xu Lin, Temme Sebastian, Bersch Klare, Hyland Stephen, Yin Jianyi, Burstein Ezra, Bahnson Brian J, Gildersleeve Jeffrey C, Grimes Catherine Leimkuhler, Reinecker Hans-Christian
Division of Digestive and Liver Diseases, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE, USA.
Nat Commun. 2025 Feb 21;16(1):1864. doi: 10.1038/s41467-025-57126-9.
Peptidoglycan recognition proteins (PGLYRPs) are implicated in the control of the intestinal microbiota; however, molecular requirements for peptidoglycan (PGN) binding and receptor signaling mechanisms remain poorly understood. Here we show that PGLYRP1 is a receptor for the disaccharide motif of lysine N-acetylglucosamine N-acetylmuramic tripeptide (GMTriP-K). PGLYRP1 is required for innate immune activation by GMTriP-K but not muramyl dipeptide (MDP). In macrophages, intracellular PGLYRP1 complexes with NOD2 and GEF-H1, both of which are required for GMTriP-K-regulated gene expression. PGLYRP1 localizes to the endoplasmic reticulum and interacts at the Golgi with NOD2 upon GMTriP-K stimulation. PGLYRP1 and dependent gene expression signatures are induced in both mouse intestinal inflammation and human ulcerative colitis. Importantly, PGLYRP1 activation by GMTriP-K can result in the protection of mice from TNBS-induced colitis. Mammalian PGLYRPs can function as intracellular pattern recognition receptors for the control of host defense responses in the intestine.
肽聚糖识别蛋白（PGLYRPs）参与肠道微生物群的调控；然而，对于肽聚糖（PGN）结合的分子要求和受体信号传导机制仍知之甚少。在此，我们表明PGLYRP1是赖氨酸N - 乙酰葡糖胺N - 乙酰胞壁酸三肽（GMTriP - K）二糖基序的受体。GMTriP - K而非胞壁酰二肽（MDP）激活天然免疫需要PGLYRP1。在巨噬细胞中，细胞内的PGLYRP1与NOD2和GEF - H1形成复合物，这两者都是GMTriP - K调节基因表达所必需的。PGLYRP1定位于内质网，在GMTriP - K刺激下于高尔基体与NOD2相互作用。在小鼠肠道炎症和人类溃疡性结肠炎中均诱导了PGLYRP1及相关基因表达特征。重要的是，GMTriP - K激活PGLYRP1可使小鼠免受三硝基苯磺酸诱导的结肠炎。哺乳动物的PGLYRPs可作为细胞内模式识别受体，用于控制肠道中的宿主防御反应。
