1. Academic Validation
  2. Cutting Edge: identification of neutrophil PGLYRP1 as a ligand for TREM-1

Cutting Edge: identification of neutrophil PGLYRP1 as a ligand for TREM-1

  • J Immunol. 2015 Feb 15;194(4):1417-21. doi: 10.4049/jimmunol.1402303.
Christine B Read 1 Joseph L Kuijper 2 Siv A Hjorth 3 Mark D Heipel 2 Xiaoting Tang 2 Andrew J Fleetwood 1 Jeffrey L Dantzler 2 Susanne N Grell 1 Jesper Kastrup 1 Camilla Wang 2 Cameron S Brandt 2 Anker J Hansen 1 Nicolai R Wagtmann 1 Wenfeng Xu 2 Vibeke W Stennicke 4
Affiliations

Affiliations

  • 1 Novo Nordisk A/S, DK-2760 Måløv, Denmark; and.
  • 2 Novo Nordisk Research Center, Seattle, WA 98109.
  • 3 Novo Nordisk A/S, DK-2760 Måløv, Denmark; and Novo Nordisk Research Center, Seattle, WA 98109.
  • 4 Novo Nordisk A/S, DK-2760 Måløv, Denmark; and vws@novonordisk.com.
Abstract

Triggering receptor expressed on myeloid cells (TREM)-1 is an Orphan Receptor implicated in innate immune activation. Inhibition of TREM-1 reduces sepsis in mouse models, suggesting a role for it in immune responses triggered by bacteria. However, the absence of an identified ligand has hampered a full understanding of TREM-1 function. We identified complexes between peptidoglycan recognition protein 1 (PGLYRP1) and bacterially derived peptidoglycan that constitute a potent ligand capable of binding TREM-1 and inducing known TREM-1 functions. Interestingly, multimerization of PGLYRP1 bypassed the need for peptidoglycan in TREM-1 activation, demonstrating that the PGLYRP1/TREM-1 axis can be activated in the absence of Bacterial products. The role for PGLYRP1 as a TREM-1 activator provides a new mechanism by which bacteria can trigger myeloid cells, linking two known, but previously unrelated, pathways in innate immunity.

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