PGLYRP1-mediated intracellular peptidoglycan detection promotes intestinal mucosal protection.

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Tác giả: Brian J Bahnson, Klare Bersch, Ezra Burstein, Shuyuan Chen, Alka Diwaker, Jeffrey C Gildersleeve, Sudershan Gondi, Catherine Leimkuhler Grimes, Lei Guo, Stephen Hyland, Xi Li, Shuzhen Liu, Rachel Putnik, Hans-Christian Reinecker, Sebastian Temme, Marina Vasconcelos, Lin Xu, Jianyi Yin, Junhui Zhou

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Nature communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 489655

 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.
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