Cited by 1,284Inflammation biomarkers and pathwaysImmune Response and InflammationNeutrophil, Myeloperoxidase and Oxidative Mechanisms

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Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes

Bouchon, Axel, Dietrich, Jes, Colonna, Marco·2000·The Journal of Immunology

DOI 10.4049/jimmunol.164.10.4991

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Abstract

We have identified new activating receptors of the Ig superfamily expressed on human myeloid cells, called TREM (triggering receptor expressed on myeloid cells). TREM-1 is selectively expressed on blood neutrophils and a subset of monocytes and is up-regulated by bacterial LPS. Engagement of TREM-1 triggers secretion of IL-8, monocyte chemotactic protein-1, and TNF-alpha and induces neutrophil degranulation. Intracellularly, TREM-1 induces Ca2+ mobilization and tyrosine phosphorylation of extracellular signal-related kinase 1 (ERK1), ERK2 and phospholipase C-gamma. To mediate activation, TREM-1 associates with the transmembrane adapter molecule DAP12. Thus, TREM-1 mediates activation of neutrophil and monocytes, and may have a predominant role in inflammatory responses.

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Background
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“At the beginning of the 21st century, triggering receptors expressed on myeloid cells (TREMs) as a new class of receptors were identified (22,23).”
Inhibiting triggering receptor expressed on myeloid cells 1 signaling to ameliorate skin fibrosis
Bale, S., Verma, P., Yalavarthi, B., Bajželj, M., Hasan, S. A. M., Silverman, J. N., Broderick, K. T., Shah, K. A., Hamill, T., Khanna, D., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.176319 · Cited by 6
“Upregulation of TREM-1 on immune cells is implicated in acute inflammation (7, 13), while sustained TREM-1 activation plays a crucial role in sepsis, arthritis, and colitis (11, 13–16).”
Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors
Wu, X., Han, X., Zhu, H., Li, M., Gong, L., Jing, S., Xie, W., Liu, Z., Li, C., & Zhang, Y. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03296-9 · Cited by 6
TREM2-Positive Lipid-Associated Macrophages (LAMs) Control White Adipose Tissue Remodeling and Metabolic Adaptation in Obesity
Worthmann, A., & Heeren, J. (2020) · Immunometabolism · doi:10.20900/immunometab20200014 · Cited by 5
“Initially, TREM2 was identified in monocytes and macrophages where it has been shown to regulate inflammatory processes [12,13].”
Background
Anti-Inflammatory Effect of Charantadiol A, Isolated from Wild Bitter Melon Leaf, on Heat-Inactivated Porphyromonas gingivalis-Stimulated THP-1 Monocytes and a Periodontitis Mouse Model
Tsai, T.-H., Chang, C., Hung, Y.-L., Huang, W.-C., Chang, H., Kuo, Y., Chyuan, J., Chuang, L., & Tsai, P. (2021) · Molecules · doi:10.3390/molecules26185651 · Cited by 6
“Co-triggering of TREM-1 and TLR4 results in a synergistic increase in TLR4-mediated pro-inflammatory cytokine and chemokine secretion [20].”
Background
Transcriptomic analysis of the chorioallantois in equine premature placental separation
MURASE, H., Ali, H. E., Ruby, R. E., Scoggin, K. E. S., & Ball, B. A. (2022) · Equine Veterinary Journal · doi:10.1111/evj.13602 · Cited by 6
Computational saturation mutagenesis to explore the effect of pathogenic mutations on extra-cellular domains of TREM2 associated with Alzheimer’s and Nasu-Hakola disease
Swain, P. S., Panda, S., Pati, S., & Dehury, B. (2023) · Journal of Molecular Modeling · doi:10.1007/s00894-023-05770-7 · Cited by 6
Soluble Triggering Receptor Expressed on Myeloid cells-1: Role in the Diagnosis of Pleural Effusions
Kim, J., Park, E.-Y., Kim, W.-H., et al. (2007) · Tuberculosis & respiratory diseases · doi:10.4046/trd.2007.62.4.290 · Cited by 6
Generation and Characterization of Two Novel Monoclonal Antibodies Produced Against Human TLT-2 Molecule
Xu, J., Gao, F., Fu, F., et al. (2013) · Monoclonal Antibodies in Immunodiagnosis and Immunotherapy · doi:10.1089/mab.2012.0086 · Cited by 6
“Triggering receptors expressed by myeloid cells (TREM) are an example of one of these kinds of receptor.((14)) Trem-like transcript 2 (TLT-2) gene is one of the conserved TREM family members, which is expressed on B cells,((15)) T cells , macrophages, and neutrophils.”
Background
Effect of Subcutaneous Glucose Sensor Implantation on Skin mRNA Expression in Pigs
Kvist, P. H., Iburg, T. M., Dawson, H. D., & Jensen, H. E. (2010) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2010.0041 · Cited by 6
“TREM1 and TREM2 are newly discovered receptors: TREM1 activates and stimulates degranulation of IL8 and myeloperoxidase from neutrophils and secretion of MCP-1, IL8, and TNF-a from monocytes,(43,44) whereas TREM2 is expressed on macrophages and dendritic cells but not on neutrophils and monocytes, suggesting a role in…”
Serum level of soluble triggering receptor expressed on myeloid cells-1 as a biomarker of disease activity in relapsing polychondritis
Sato, T., Yamano, Y., Tomaru, U., et al. (2013) · Modern Rheumatology · doi:10.1007/s10165-013-0833-z · Cited by 6
Perturbations of mucosal homeostasis through interactions of intestinal microbes with myeloid cells
Schey, R., Danzer, C., & Mattner, J. (2014) · Immunobiology · doi:10.1016/j.imbio.2014.11.014 · Cited by 6
“It contains an xtracellular hydrophobic signal peptide followed by a type-V Ig F domain, a transmembrane domain and a cytoplasmic domain Bouchon et al., 2000).”
BackgroundInfluential
Several MHC-Linked Ig Superfamily Genes Have Features of Ancestral Antigen-Specific Receptor Genes
Pasquier, L. D. (2002) · Current topics in microbiology and immunology · doi:10.1007/978-3-662-04700-2_5 · Cited by 6
CD Antigens 2001
Mason, D. Y., André, P., Bensussan, A., et al. (2002) · Modern Pathology · doi:10.1038/modpathol.3880492 · Cited by 6
“Highest levels on neutrophils, monocytes, and macrophages Novel EGF-TM7 molecule; interacts with a surface ligand on myeloid cells (23) Flt-1 (VEGFR-1) Endothelial cells, monocytes (24) GPRv53 390 aa Leukocytes Identified by gene cloning; G-protein– coupled histamine receptor (25) IRTA1 and IRTA2 Subpopulations of B c…”
Background
Nouveaux acteurs de l’immunité innée : les récepteurs TREM
Gibot, S. (2004) · médecine/sciences · doi:10.1051/medsci/2004205503 · Cited by 6
Mitochondrial Electron Transport Chain Inhibition Suppresses LPS-Induced Inflammatory Responses via TREM1/STAT3 Pathway in BV2 MicrogliaPreprint
Zhou, C., Zhang, J., & Ying, W. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.25.888529 · Cited by 6
“A number of studies have suggested that TREMs play important regulatory roles in inflammation (20-22).”
Background
Commentary: Triggering Receptor Expressed on Myeloid Cells-1 Inhibitor Targeted to Endothelium Decreases Cell Activation
Sigalov, A. B. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00173 · Cited by 6
The properties of TREM1 and its emerging role in pain-related diseases
Fan, Z., Wang, L., Sun, S., & Ge, Z. (2025) · Molecular Brain · doi:10.1186/s13041-025-01187-w · Cited by 7
“The initial belief was that TREM1 is primarily expressed on the surface of neutrophils and monocytes [13].”
The TREM Receptor Family in Cardiovascular Diseases: Functions, Mechanisms and Therapeutic Perspectives
Liu, W., Liu, Y., Guo, X., Cao, C., Weng, S., & Peng, D. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116167 · Cited by 5
Damage-associated molecular patterns and sensing receptors based molecular subtypes in malignant pleural mesothelioma and implications for immunotherapy
Liu, Z., Wan, R., Bai, H., & Wang, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1104560 · Cited by 6
The Role of TREM-1 Gene Expression and Soluble TREM-1 as Prognostic Markers of Sepsis
Atef, D. M., & Ghonaim, R. A. (2016) · Journal of Medical Microbiology & Diagnosis · doi:10.4172/2161-0703.1000211 · Cited by 5
“Triggering receptor expressed on myeloid cells-1 (TREM-1) was first described in the year 2000 [3], is a member of immunoglobulin (Ig) superfamily receptor expressed on polymorphonuclear granulocytes and mature monocytes, stimulation by bacteria or fungus infection may cause up-regulation for TREM-1 expression and tra…”
Background
Serum Presepsin, Proadrenomedullin and Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) as Biomarkers for the Diagnosis of Acute Pyelonephritis
Çetin, N., Kiraz, Z. K., & Gençler, A. (2020) · Indian Pediatrics · doi:10.1007/s13312-020-1914-7 · Cited by 5
Triggering receptor expressed on myeloid cells-1 deletion in mice attenuates high-fat diet-induced obesity
Brustolin, B., Touly, N., Maillefer, M., Parisot, L., Pillo, E. D., Derive, M., & Gibot, S. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.983827 · Cited by 5
BDNF, sHLA-G, and sTREM-1 are useful blood biomarkers for identifying grade IV glioma patients
Klučková, K., Kozak, J., Švajdler, M., Štěňo, J., Matejčı́k, V., Ďurmanová, V., Zsemlye, E., & Bucová, M. (2023) · Neoplasma · doi:10.4149/neo_2023_221129n1147 · Cited by 5
Persistently Elevated Soluble Triggering Receptor Expressed on Myeloid Cells 1 and Decreased Monocyte Human Leucocyte Antigen DR Expression Are Associated With Nosocomial Infections in Septic Shock Patients
Venet, M., Bidar, F., Derive, M., et al. (2023) · Critical Care Explorations · doi:10.1097/cce.0000000000000869 · Cited by 5
TREM-1 as a potential prognostic biomarker associated with immune infiltration in clear cell renal cell carcinoma
Pu, Y., Cai, D., Jin, L., Xu, F., Ye, E., Wu, L., Mo, L., Liu, S., Guo, Q., & Wu, G. (2023) · World Journal of Surgical Oncology · doi:10.1186/s12957-023-03013-w · Cited by 5
“TREM-1 is involved in triggering DAP12 association and Src family kinase-mediated phosphorylation of ITAM tyrosine on cell membranes [10–12], followed by recruitment and phosphorylation of GRBP-2, Syk, and ZAP70, thereby initiating downstream signal transduction [10, 11, 13].”
Background
The expression IL1B correlates negatively with the clinical response to adalimumab in Crohn's disease patients: An ex vivo approach using peripheral blood mononuclear cells
Gole, B., Pernat, C., Jezernik, G., et al. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121822 · Cited by 5
Unveiling the significance of TREM1/2 in hemorrhagic stroke: structure, function, and therapeutic implications
Kong, Y., Wang, D., Jin, X., Liu, Y., & Xu, H. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1334786 · Cited by 6
sTREM-1 in bronchoalveolar lavage fluid in patients with pulmonary sarcoidosis, effect of smoking and inflammation
Suchánková, M., Bucová, M., Tibenská, E., et al. (2013) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2013_148 · Cited by 5
Blockade of Triggering receptor expressed on myeloid cells-1 as a new therapy of arthritis
Iwai, H., & Kohsaka, H. (2012) · Japanese Journal of Clinical Immunology · doi:10.2177/jsci.35.81 · Cited by 5
Targeting Intramembrane Protein–Protein Interactions: Novel Therapeutic Strategy of Millions Years Old
Sigalov, A. B. (2017) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2017.06.004 · Cited by 5
“Initial findings established TREM-1 as an amplifier of the systemic inflammatory response syndrome associated with sepsis (Bouchon, Dietrich, & Colonna, 2000; Bouchon et al., 2001) .”
sTREM-1 as a diagnostic biomarker for acute appendicitis in children
Klein, T. T., Kohn, E., Klin, B., et al. (2021) · Asian Journal of Surgery · doi:10.1016/j.asjsur.2021.02.025 · Cited by 5
Glycoprotein Pathways Altered in Frontotemporal Dementia With Autoimmune Disease
Bright, F., Katzeff, J. S., Hodges, J. R., Piguet, O., Kril, J. J., Halliday, G. M., & Kim, W. S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.736260 · Cited by 5
Mice Lacking PECAM-1 and Ceacam1 Have Enhanced Platelet Secretion and Thrombus Growth: Novel Link with PAR4
Kuriri, F. A., Burchall, G., Alanazi, F. G., et al. (2021) · Thrombosis and Haemostasis · doi:10.1055/a-1663-8108 · Cited by 5
Comparison of gastric juice soluble triggering receptor expressed on myeloid cells and C-reactive protein for detection of Helicobacter pylori infection
Piroozmand, A., Soltani, B., Razavizadeh, M., et al. (2017) · Electronic physician · doi:10.19082/6111 · Cited by 5
“Triggering receptor expressed on myeloid cells (TREM-1) is a receptor that is expressed on the surface of monocytes and neutrophils in acute inflammatory processes such as sepsis, and is increased by bacteria and fungus (5, 6).”
Background
A promising novel biomarker for early-onset preeclampsia: soluble trigger receptor expressed on myeloid cells-1 (sTREM-1)
Turhan, U., & Ertaş, S. (2020) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2020.1846706 · Cited by 5
Elevated Plasma Soluble Triggering Receptor Expressed on Myeloid Cells‐1 Level in Patients with Acute Coronary Syndrome (ACS): A Biomarker of Disease Severity and Outcome
Shiber, S., Kliminski, V., Orvin, K., Sagy, I., Vaturi, M., Kornowski, R., Drescher, M. J., & Molad, Y. (2021) · Mediators of Inflammation · doi:10.1155/2021/8872686 · Cited by 5
“The TREM-1-mediated proinflammatory effect has been identified in various infectious and noninfectious inflammatory conditions [9] including atherosclerosis [13].”
Influential
Diagnostic value of TREM-1 and TREM-2 expression in bronchoalveolar lavage fluid in sarcoidosis and other lung diseases
Bucová, M., Suchánková, M., Tibenská, E., Majer, I., Novosadova, H., & Urban, S. K. (2015) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2015_139 · Cited by 5

Authors: Bouchon, A., Dietrich, J., & Colonna, M.
Affiliations: Basel Institute for Immunology , Basel ,
ORCID: Dietrich, Jes
Colonna, Marco
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2000-05
Volume: 164
Issue: 10
Pages: 4991-4995
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.164.10.4991
OpenAlex: W2149698238
Semantic Scholar: c6fffd66acdcb27c928605f7aca443056a3a6c3f
Cited by: 1,284
References: 13
Citations by year: 2026: 38 · 2025: 47 · 2024: 73 · 2023: 87 · 2022: 51 · 2021: 65 · 2020: 83 · 2019: 49 · 2018: 55 · 2017: 51 · 2016: 59 · 2015: 47 · 2014: 48 · 2013: 68 · 2012: 50
FWCI: 6.50
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords: TREM-1, neutrophils, monocytes, inflammation, IL-8 secretion, MCP-1, TNF-α, neutrophil degranulation, calcium mobilization, phospholipase C-gamma, myeloid cell activation
MeSH terms: Triggering Receptor Expressed on Myeloid Cells-1, Amino Acid Sequence, Fungi, Multigene Family, Gram-Negative Bacteria, Gram-Positive Bacteria, Humans, Immunoglobulins, Inflammation, Macrophage Activation, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, Molecular Weight, Monocytes, Neutrophils, Phosphorylation, Receptors, Immunologic, Tyrosine, Biomarkers, Up-Regulation, Cytokines, Neutrophil Activation, Chemokines, Calcium Signaling, Adaptor Proteins, Signal Transducing

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Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes

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