Clinical review: role of triggering receptor expressed on myeloid cells-1 during sepsis

Abstract

Triggering receptor expressed on myeloid cells (TREM)-1 is a recently identified molecule that is involved in monocytic activation and in the inflammatory response. It belongs to a family related to the natural killer cell receptors and is expressed on neutrophils, mature monocytes and macrophages. The inflammatory response mediated by Toll-like receptor-2 and -4 stimulation is amplified by the engagement of TREM-1. The expression of membrane-bound TREM-1 is greatly increased on monocytes during sepsis. Moreover, infection induces the release of a soluble form of this receptor, which can be measured in biological fluid and may be useful as a diagnostic tool. Modulation of the TREM-1 signalling pathway by the use of small synthetic peptides confers interesting survival advantages during experimental septic shock in mice, even when this teatment is administered late after the onset of sepsis.

Figure 1

TREM-1 expression and release in healthy volunteers administered lipopolysaccharide. (a) TREM-1 cell surface expression in healthy volunteers administered 4 ng/kg lipopolysaccharide intravenously. (b) Corresponding plasma concentrations of the soluble form of TREM-1. Adapted with permission from Knapp and coworkers [21]. LPS, lipopolysaccharide; TREM, triggering receptor expressed on myeloid cells.

Figure 2

Time course of median plasma levels of sTREM-1 in septic patients. Patients are subgrouped according to whether they survived (squares; n = 42) or did not survive (triangles; n = 21). Adapted with permission from Gibot and coworkers [29]. sTREM, soluble triggering receptor expressed on myeloid cells.

Figure 3

Overview of the role of TREM-1 in sepsis. DAG, diacylglycerol; ERK, extracellular signal regulated kinase; GRB, growth factor receptor binding protein; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; PAMP, pathogen-associated molecular pattern; PI3K, phosphatidylinositol 3-kinase; PKC, protein kinase C; PLC, phospholipase C; SOS, son of sevenless; TLR, Toll-like receptor; TREM, triggering receptor expressed on myeloid cells; TREM-1L, TREM-1 ligand.