title: Regulation of triggering receptor expressed on myeloid cells 1 expression on mouse inflammatory monocytes.
abstract: Triggering receptor expressed on myeloid cells 1 (TREM-1) is an activating receptor involved in inflammatory diseases and septic shock. The TREM-1 ligand(s) (TREM-1L) have not yet been identified. In this study, we performed a detailed analysis of the expression of mouse TREM-1 and its ligand(s). Our results demonstrate that TREM-1 is expressed on bone-marrow-derived dendritic cells (BMDC). On bone-marrow-derived macrophages (BMM) its expression is induced in vitro after stimulation by granulocyte-macrophage colony-stimulating factor, interleukin-3 or by myeloid differentiation primary response gene 88 (MyD88)-dependent Toll-like receptor (TLR) ligands. Under steady-state conditions mouse TREM-1 is detectable on a Gr-1(-) F4/80(+) monocyte subpopulation bearing markers of resident monocytes, but not on Gr-1(+) F4/80(+) inflammatory monocytes. During lipopolysaccharide (LPS)-induced endotoxaemia TREM-1 was also up-regulated on inflammatory Gr-1(+) F4/80(+) cells in vivo. In tumour-bearing mice, TREM-1 was up-regulated on Gr-1(+) F4/80(+) monocytes, which phenotypically and functionally resembled mononuclear myeloid-derived suppressor cells. Using a soluble TREM-1 fusion protein, we demonstrate that after intravenous injection of LPS TREM-1L was induced on Gr-1(+) granulocytes and monocytes but not on other cell populations in peripheral blood. This up-regulation on granulocytes was directly mediated by TLR ligands and required the adapter protein MyD88. In contrast to human, mouse platelets expressed TREM-1L neither under steady-state conditions nor after LPS injection in vivo. Our study reveals differential regulation of TREM-1 expression on mouse monocyte subpopulations and improves our understanding of the biological role of TREM-1 during disease.
authors.affiliation: German Cancer Research Centre (DKFZ), Innate Immunity, 69120 Heidelberg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Zanzinger
authors.forename: Carola
authors.initials: C
authors.lastname: Schellack
authors.forename: Norman
authors.initials: N
authors.lastname: Nausch
authors.forename: Adelheid
authors.initials: A
authors.lastname: Cerwenka
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D019446:Endotoxemia / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006098:Granulocytes / Q000276:immunology; D007113:Immunity, Innate; D007377:Interleukin-3 / Q000276:immunology; D008024:Ligands; D016399:Lymphoma, T-Cell / Q000276:immunology; D008562:Membrane Glycoproteins / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D009368:Neoplasm Transplantation; D011971:Receptors, Immunologic / Q000097:blood*; D051193:Toll-Like Receptors / Q000276:immunology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007377:Interleukin-3; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D051193:Toll-Like Receptors; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor