title: Cutting Edge: identification of neutrophil PGLYRP1 as a ligand for TREM-1.
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.
authors.affiliation: Novo Nordisk A/S, DK-2760 Måløv, Denmark; and.
authors.forename: Christine B
authors.initials: CB
authors.lastname: Read
authors.affiliation: Novo Nordisk Research Center, Seattle, WA 98109.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kuijper
authors.affiliation: Novo Nordisk A/S, DK-2760 Måløv, Denmark; and Novo Nordisk Research Center, Seattle, WA 98109.
authors.forename: Siv A
authors.initials: SA
authors.lastname: Hjorth
authors.affiliation: Novo Nordisk Research Center, Seattle, WA 98109.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Heipel
authors.affiliation: Novo Nordisk Research Center, Seattle, WA 98109.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Tang
authors.affiliation: Novo Nordisk A/S, DK-2760 Måløv, Denmark; and.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Fleetwood
authors.affiliation: Novo Nordisk Research Center, Seattle, WA 98109.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Dantzler
authors.affiliation: Novo Nordisk A/S, DK-2760 Måløv, Denmark; and.
authors.forename: Susanne N
authors.initials: SN
authors.lastname: Grell
authors.affiliation: Novo Nordisk A/S, DK-2760 Måløv, Denmark; and.
authors.forename: Jesper
authors.initials: J
authors.lastname: Kastrup
authors.affiliation: Novo Nordisk Research Center, Seattle, WA 98109.
authors.forename: Camilla
authors.initials: C
authors.lastname: Wang
authors.affiliation: Novo Nordisk Research Center, Seattle, WA 98109.
authors.forename: Cameron S
authors.initials: CS
authors.lastname: Brandt
authors.affiliation: Novo Nordisk A/S, DK-2760 Måløv, Denmark; and.
authors.forename: Anker J
authors.initials: AJ
authors.lastname: Hansen
authors.affiliation: Novo Nordisk A/S, DK-2760 Måløv, Denmark; and.
authors.forename: Nicolai R
authors.initials: NR
authors.lastname: Wagtmann
authors.affiliation: Novo Nordisk Research Center, Seattle, WA 98109.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Xu
authors.affiliation: Novo Nordisk A/S, DK-2760 Måløv, Denmark; and vws@novonordisk.com.
authors.forename: Vibeke W
authors.initials: VW
authors.lastname: Stennicke
mesh_terms: D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D047468:Immunoprecipitation; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D020349:Surface Plasmon Resonance; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D016207:Cytokines; D008024:Ligands; D008562:Membrane Glycoproteins; C491878:PGLYRP1 protein, human; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1