PGLYRP1-mediated intracellular peptidoglycan detection promotes intestinal mucosal protection
Date
2025-02-21
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Communications
Abstract
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.
Description
This article was originally published in Nature Communications. The version of record is available at: https://doi.org/10.1038/s41467-025-57126-9.
© The Author(s) 2025.
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Keywords
antimicrobial responses, mucosal immunology
Citation
Chen, S., Putnik, R., Li, X. et al. PGLYRP1-mediated intracellular peptidoglycan detection promotes intestinal mucosal protection. Nat Commun 16, 1864 (2025). https://doi.org/10.1038/s41467-025-57126-9