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PGLYRP1-mediated intracellular peptidoglycan detection promotes intestinal mucosal protection

Author

Listed:
  • Shuyuan Chen

    (University of Texas Southwestern Medical Center)

  • Rachel Putnik

    (University of Delaware)

  • Xi Li

    (University of Texas Southwestern Medical Center)

  • Alka Diwaker

    (University of Texas Southwestern Medical Center)

  • Marina Vasconcelos

    (University of Delaware)

  • Shuzhen Liu

    (University of Texas Southwestern Medical Center)

  • Sudershan Gondi

    (University of Texas Southwestern Medical Center)

  • Junhui Zhou

    (University of Delaware)

  • Lei Guo

    (University of Texas Southwestern Medical Center)

  • Lin Xu

    (University of Texas Southwestern Medical Center)

  • Sebastian Temme

    (National Cancer Institute)

  • Klare Bersch

    (University of Delaware)

  • Stephen Hyland

    (University of Delaware)

  • Jianyi Yin

    (University of Texas Southwestern Medical Center)

  • Ezra Burstein

    (University of Texas Southwestern Medical Center)

  • Brian J. Bahnson

    (University of Delaware)

  • Jeffrey C. Gildersleeve

    (National Cancer Institute)

  • Catherine Leimkuhler Grimes

    (University of Delaware)

  • Hans-Christian Reinecker

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

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.

Suggested Citation

  • Shuyuan Chen & Rachel Putnik & Xi Li & Alka Diwaker & Marina Vasconcelos & Shuzhen Liu & Sudershan Gondi & Junhui Zhou & Lei Guo & Lin Xu & Sebastian Temme & Klare Bersch & Stephen Hyland & Jianyi Yin, 2025. "PGLYRP1-mediated intracellular peptidoglycan detection promotes intestinal mucosal protection," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57126-9
    DOI: 10.1038/s41467-025-57126-9
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    References listed on IDEAS

    as
    1. Che A. Stafford & Alicia-Marie Gassauer & Carina C. Oliveira Mann & Maria C. Tanzer & Evelyn Fessler & Benedikt Wefers & Dennis Nagl & Gunnar Kuut & Karolina Sulek & Catherine Vasilopoulou & Sophia J., 2022. "Phosphorylation of muramyl peptides by NAGK is required for NOD2 activation," Nature, Nature, vol. 609(7927), pages 590-596, September.
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