[HTML][HTML] Cutting edge: identification of neutrophil PGLYRP1 as a ligand for TREM-1

CB Read, JL Kuijper, SA Hjorth, MD Heipel… - The Journal of …, 2015 - journals.aai.org
CB Read, JL Kuijper, SA Hjorth, MD Heipel, X Tang, AJ Fleetwood, JL Dantzler, SN Grell…
The Journal of Immunology, 2015journals.aai.org
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 …
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.
journals.aai.org