TREM-1 (triggering receptor expressed on myeloid cells): a new player in acute inflammatory responses.
TREM-1 (triggering receptor expressed on myeloid cells), a recently discovered receptor of the immunoglobulin superfamily, activates neutrophils and monocytes/macrophages by signaling through the adapter protein DAP12. TREM-1 is the best-characterized member of a growing family of DAP12-associated receptors that regulate the function of myeloid cells in innate and adaptive responses. TREM-1 amplifies Toll-like receptor-initiated responses against microbial challenges and potentiates the secretion of proinflammatory chemokines and cytokines in response to bacterial and fungal infections. Blockade of TREM-1 reduces inflammation and increases survival in animal models of bacterial infections that cause systemic hyperinflammatory syndromes. The TREM-1 ligands are not known. Characterization of TREM-1 natural ligands will further illuminate the mechanisms regulating innate responses against pathogens. Whatever the ligands, targeted activation or blockade of TREM-1 and its ligands may help maximize the efficacy of existing treatments for sepsis.
Colonna
Marco
M
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. mcolonna@pathology.wustl.edu
Facchetti
Fabio
F
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C498715:TREM2 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1