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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BackgroundInfluential
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BackgroundInfluential
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Background
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Background
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BackgroundInfluential
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Background
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Background
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BackgroundResult
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Hörner, C., Bouchon, A., Bierhaus, A., Nawroth, P. P., Martin, E., Bardenheuer, H., & Weigand, M. A. (2004) · Der Anaesthesist · doi:10.1007/s00101-003-0626-4 · Cited by 26
sTREM-1 is a potential useful biomarker for exclusion of ongoing infection in patients with secondary peritonitis
Determann, R. M., van Till, J. W. O., van Ruler, O., van Veen, S. Q., Schultz, M. J., & Boermeester, M. A. (2009) · Cytokine · doi:10.1016/j.cyto.2008.12.006 · Cited by 24
“The triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently discovered cell-surface protein that is expressed by neutrophils and a subset of monocytes and macrophages [13].”
Background
Plasma levels of eight different mediators and their potential as biomarkers of various clinical malaria conditions in African children
Tahar, R., Albergaria, C., Zeghidour, N., Ngane, V. F., Basco, L. K., & Roussilhon, C. (2016) · Malaria Journal · doi:10.1186/s12936-016-1378-3 · Cited by 24
“Similarly, sTREM-1, which is an effective marker for chronic exacerbated inflammation [47, 48], was also lower in AM children than in control samples, possibly reflecting controlled inflammatory conditions in these individuals.”
TREM-1 and TREM-2 Expression on Blood Monocytes Could Help Predict Survival in High-Grade Glioma Patients
Klučková, K., Kozak, J., Szabóová, K., Rychlý, B., Švajdler, M., Suchánková, M., Tibenská, E., Filová, B., Steno, J., Matejčı́k, V., et al. (2020) · Mediators of Inflammation · doi:10.1155/2020/1798147 · Cited by 24
“Elevated serum/plasma levels of sTREM-1 were found in inflammatory diseases of both infectious and noninfectious origins [18, 19].”
Background
Neutrophils: Neglected Players in Viral Diseases
Gabriel, C., Her, Z., & Ng, L. F. P. (2013) · DNA and Cell Biology · doi:10.1089/dna.2013.2211 · Cited by 23
“TREM-1 (triggering receptors expressed in myeloid cells-1), a neutrophil surface protein (Bouchon et al. , 2000), has been reported to bind to the surface glycoprotein (GP) expressed by the ﬁlovirus Marburg virus (MARV) (Fig.”
Modulation of Paired Immunoglobulin-Like Type 2 Receptor Signaling Alters the Host Response toStaphylococcus aureus-Induced Pneumonia
Banerjee, A., Stevenaert, F., Pande, K., Haghjoo, E., Antonenko, S. V., Gorman, D., Sathe, M., McClanahan, T. K., Pierce, R. H., Turner, S. P., et al. (2010) · Infection and Immunity · doi:10.1128/iai.00969-09 · Cited by 24
“Additionally, the activating receptors MDL-1 (4) and the TREMs (6), which associate with DAP12, were implicated in mycobacterial infections and in the diagnosis of lung infections.”
Background
Transcript profiles of dendritic cells of PLOSL patients link demyelinating CNS disorders with abnormalities in pathways of actin bundling and immune response
Kiialainen, A., Veckman, V., Saharinen, J., Paloneva, J., Gentile, M., Hakola, P., Hemelsoet, D., Ridha, B., Kopra, O., Julkunen, I., et al. (2007) · Journal of molecular medicine · doi:10.1007/s00109-007-0191-4 · Cited by 31
“The DAP12/TREM2 protein complex is expressed on the surface of monocytederived dendritic cells (DCs) [10].”
Background
Expression of soluble triggering receptor expression on myeloid cells-1 in pleural effusion
Huang, L., Shi, H., LIANG, Q.-L., et al. (2008) · Chinese Medical Journal · doi:10.1097/00029330-200809010-00012 · Cited by 24
DIAGNOSTIC MARKERS OF SEPSIS IN THE EMERGENCY DEPARTMENT
Spapen, H. D., Hachimi-Idrissi, S., Corne, L., et al. (2006) · Acta Clinica Belgica · doi:10.1179/acb.2006.022 · Cited by 24
Impact of delayed antimicrobial therapy in septic ITU patients
Frost, R. E., Newsham, H., Parmar, S., & González-Ruiz, A. (2010) · Critical Care · doi:10.1186/cc9123 · Cited by 24
TREM1: A Potential Therapeutic Target For Alzheimer’s Disease
Saadipour, K. (2017) · Neurotoxicity Research · doi:10.1007/s12640-017-9716-y · Cited by 25
“Triggering receptor expressed on myeloid cells -1 (TREM1) and -2 (TREM2) are members of TREM family and belong to the immunoglobulin variable (IgV) domain receptor superfamily of proteins (Bouchon et al. 2000).”
Triterpenoid compound betulin attenuates allergic airway inflammation by modulating antioxidants, inflammatory cytokines and tissue transglutaminase in ovalbumin-induced asthma mice model
Kamaraj, Y., Dhayalan, S., Chinnaiyan, U., et al. (2021) · Journal of Pharmacy and Pharmacology · doi:10.1093/jpp/rgab015 · Cited by 23
scCASE: accurate and interpretable enhancement for single-cell chromatin accessibility sequencing data
Tang, S., Cui, X., Wang, R., Li, S., Li, S., Huang, X., & Chen, S. (2024) · Nature Communications · doi:10.1038/s41467-024-46045-w · Cited by 23
Inhibition of Innate Co-Receptor TREM-1 Signaling Reduces CD4+ T Cell Activation and Prolongs Cardiac Allograft Survival
Schiechl, G., Brunner, S. M., Kesselring, R., et al. (2013) · American Journal of Transplantation · doi:10.1111/ajt.12186 · Cited by 23
“However, modulating the innate immune system by influencing cell intrinsic regulatory mechanisms (26,30–33), such as TREM1 (7,9,18,19,34) is feasible.”
BackgroundInfluential
New markers in pneumonia
Cheng, C.-W., Chien, M., Su, S.-C., & Yang, S.-F. (2013) · Clinica Chimica Acta · doi:10.1016/j.cca.2013.01.011 · Cited by 23
“Once the TREM binds to its ligand and is activated through the association with the adapter protein, DAP12, it can further induce the secretion of inflammatory cytokines, such as IL-8, monocyte chemotactic protein-1, and TNF-α to induce neutrophil degranulation in response to infections [65].”
Background
Inflammatory Marker sTREM-1 Reflects the Clinical Stage and Respiratory Tract Obstruction in Allergic Asthma Bronchiale Patients and Correlates with Number of Neutrophils
Bucová, M., Suchánková, M., Dzurilla, M., et al. (2012) · Mediators of Inflammation · doi:10.1155/2012/628754 · Cited by 23
“Myeloid cells activation upon a ligand binding to this receptor generally results in inflammatory response amplification, enhanced production of proinflammatory mediators, mainly of tumour necrosis factor-alfa (TNF-α and of interleukin-8 (IL-8) [2, 10], increased expression of costimulatory molecules on the surface of…”
Background
Association of Serum Myeloid Cells of Soluble Triggering Receptor-1 Level with Myocardial Dysfunction in Patients with Severe Sepsis
Tao, F., Peng, L., Li, J., et al. (2013) · Mediators of Inflammation · doi:10.1155/2013/819246 · Cited by 23
“in 2000 [4], is amember of the immunoglobulin superfamily of receptors that is specifically expressed on the surfaces of monocytes and neutrophils.”
Background
Monocyte TREM-1 membrane expression in non-infectious inflammation
Cavaillon, J. (2009) · Critical Care · doi:10.1186/cc7882 · Cited by 23
“Not only do these antibodies activate monocytes and neutrophils to produce cytokines [9], but they also act in synergy with TLR4, TLR3, and NOD-like receptor ligands [10,11].”
Background
Host Response Biomarkers in Sepsis: Overview on sTREM-1 Detection
Lemarie, J., Barraud, D., & Gibot, S. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1776-1_17 · Cited by 23
Enhanced expression of TREM-1 in splenic cDCs in lupus prone mice and it was modulated by miRNA-150
Gao, S., Yuan, L., Wang, Y., et al. (2016) · Molecular Immunology · doi:10.1016/j.molimm.2016.12.006 · Cited by 23
“In the presence of an inhibitng TREM-1 chimera (Bouchon et al., 2000; Bouchon et al., 2001), construct with TREM-1 protein fused to Fc region of IgG1, the ecretion of IL-6 and TNF- was significantly inhibited (Fig.”
BackgroundResult
CpG-oligodeoxynucleotide-induced TLR9 activation regulates macrophage TREM-1 expression and shedding
Molad, Y., Pokroy‐Shapira, E., & Carmon, V. (2013) · Innate Immunity · doi:10.1177/1753425913476970 · Cited by 23
s TREM ‐1 in patients with chronic kidney disease on hemodialysis
Essa, E. S., & Elzorkany, K. M. A. (2015) · Apmis · doi:10.1111/apm.12459 · Cited by 22
“A finding that could be speculated as TREM-1 was highly upregulated and has been implicated as an amplifier of inflammation (10, 36–38), functioning as an important coactivator of the TLR (6, 10, 39) and NOD Like Receptor (NLR) (40, 41) signaling pathways.”
Background
Novel Attributions of TREMs in Immunity
Pandupuspitasari, N. S., Khan, F. A., Huang, C., Chen, X., & Zhang, S. (2016) · Current Issues in Molecular Biology · doi:10.21775/cimb.020.047 · Cited by 22
Serum sTREM‐1 level is quite higher in Crimean Congo Hemorrhagic Fever, a viral infection
Altay, F. A., Elaldı, N., Şentürk, G. Ç., et al. (2016) · Journal of Medical Virology · doi:10.1002/jmv.24496 · Cited by 22
“The first Triggering Receptor Expressed on Myeloid Cells (TREM) molecule was designated in 2000 [Bouchon et al., 2000].”
Background
Triggering receptor expressed on myeloid cells and 5’adenosine monophosphate-activated protein kinase in the inflammatory response: a potential therapeutic target
Thankam, F. G., Dilisio, M. F., Dougherty, K. A., Dietz, N. E., & Agrawal, D. K. (2016) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2016.1196138 · Cited by 22
“Activation studies of TREM-1 by TLR ligands on monocytes also revealed the cumulative amplification of inflammatory cytokines [20].”
Background
Inflammatory Mediators Across the Spectrum of Ankle-Brachial Index
Gür, D. Ö., Gür, Ö., Güzel, S., Akyüz, A., Gürkan, S., Alpsoy, Ş., Gulec, N. S., & Koc, F. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.44891 · Cited by 22
The enigmatic nature of the triggering receptor expressed in myeloid cells -1 (TLT- 1)
Branfield, S. L., & Washington, A. V. (2021) · Platelets · doi:10.1080/09537104.2021.1881948 · Cited by 22
Inhibition of the Interaction of TREM-1 and eCIRP Attenuates Inflammation and Improves Survival in Hepatic Ischemia/Reperfusion
Borjas, T., Jacob, A., Yen, H.-T., Patel, V. M., Coppa, G. F., Aziz, M., & Wang, P. (2021) · Shock · doi:10.1097/shk.0000000000001894 · Cited by 23
“TREM-1 promotes inflammation by releasing cytokines and chemokines, via the activation of DNAX activating protein 12 and the spleen tyrosine kinase (14, 25).”
Background
Anticancer efficacy of monotherapy with antibodies to SIRPα/SIRPβ1 mediated by induction of antitumorigenic macrophages
Sakamoto, M., Murata, Y., Tanaka, D., Kakuchi, Y., Okamoto, T., Hazama, D., Saito, Y., Kotani, T., Ohnishi, H., Miyasaka, M., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2109923118 · Cited by 21
“Indeed, cross-linking of TREM1 by specific Abs was shown to induce TNFα secretion and MAPK activation in human monocytes (36).”
Extracellular CIRP induces acute kidney injury via endothelial TREM-1
Siskind, S., Zhang, F., Brenner, M., et al. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.954815 · Cited by 22
“Interestingly, TREM-1, which was originally identified with high expression on neutrophils, monocytes, and macrophages, has recently been identified on endothelial cells (Bouchon et al., 2000; Jolly et al., 2018).”
Background
TREM ‐1 induces pyroptosis in cardiomyocytes by activating NLRP3 inflammasome through the SMC4 / NEMO pathway
Yang, Z.-L., Pan, X., Wu, X., Lin, Q., Chen, Y., Cai, S., Zhang, Y., Mai, Z., Ahmad, N., Ma, D., et al. (2022) · FEBS Journal · doi:10.1111/febs.16644 · Cited by 22
Association between genetic variants in TREM1, CXCL10, IL4, CXCL8 and TLR7 genes with the occurrence of congenital Zika syndrome and severe microcephaly
Santos, C. N. O., Magalhães, L. S., Fonseca, A. B. D. L., Bispo, A. J. B., Porto, R. L. S., Alves, J. C., dos Santos, C. A., de Carvalho, J. V., da Silva, Â. M., Teixeira, M. M., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-30342-3 · Cited by 22
Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer’s Disease
Tamburini, B., Badami, G. D., Manna, M. P. L., Azgomi, M. S., Caccamo, N., & Dieli, F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241511922 · Cited by 22
Pleural fluid soluble triggering receptor expressed on myeloid cells-1 as a marker of bacterial infection: a meta-analysis
Summah, H. D., Tao, L., Zhu, Y., Jiang, H., & Qu, J. (2011) · BMC Infectious Diseases · doi:10.1186/1471-2334-11-280 · Cited by 22
“and is involved in inflammatory response [2,3].”
TLT2 Potentiates Neutrophil Antibacterial Activity and Chemotaxis in Response to G Protein-Coupled Receptor-Mediated Signaling
Halpert, M. M., Thomas, K. A., King, R. G., & Justement, L. B. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100534 · Cited by 22
TREM-like transcript 2 is stored in human neutrophil primary granules and is up-regulated in response to inflammatory mediators
Thomas, K. A., King, R. G., Sestero, C. M., & Justement, L. B. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.3ab1115-507r · Cited by 22
“Previous studies have shown that expression of TREM locus receptors is modulated in response to inflammatory stimuli [19, 20], and TLT2 expression is up-regulated on mouse neutrophils in response to in vivo administration of LPS [7].”
Background
Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Impairs Host Defense in Experimental Melioidosis
Weehuizen, T. A. F., Hommes, T. J., Lankelma, J. M., de Jong, H. K., Roelofs, J. J. T. H., de Vos, A. F., Colonna, M., van der Poll, T., & Wiersinga, W. J. (2016) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0004747 · Cited by 23
“TREM-1 is expressed on neutrophils and monocyte subsets [11] and amplifies pro-inflammatory TLR-mediated responses in vitro [12].”
BackgroundResult
Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis
Carneiro, M. W., Fukutani, K. F., Andrade, B. B., Curvelo, R. P., Cristal, J. R., Carvalho, A. M., Barral, A. M. P., Weyenbergh, J. V., Barral‐Netto, M., & de Oliveira, C. I. (2016) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0005116 · Cited by 24
Atorvastatin has a protective effect in a mouse model of bronchial asthma through regulating tissue transglutaminase and triggering receptor expressed on myeloid cells-1 expression
Liu, M.-W., Liu, R., Wu, H., Chen, M., Dong, M.-N., Huang, Y.-Q., Zhang, C.-H., Wang, Y.-Z., Xia, J., Shi, Y., et al. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.4576 · Cited by 21
“Under conditions of infection and inflammation, the expression levels of TREM‑1 are significantly upregulated (11).”
Idelalisib impairs TREM-1 mediated neutrophil inflammatory responses
Alflen, A., Stadler, N., Lopez, P. A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-23808-2 · Cited by 22
The triggering receptor expressed by myeloid cells-1 activates TLR4-MyD88-NF-κB-dependent signaling to aggravate ventilation-induced lung inflammation and injury in mice
Wang, X., Luo, B., Lu, Y., Pang, D., Zheng, J., Mo, J., Huang, H., & Feng, J. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2853-7 · Cited by 23
Soluble Triggering Receptor Expressed on Myeloid Cells 1 in lung cancer
Kuemmel, A., Alflen, A., Schmidt, L. H., Sebastian, M., Wiewrodt, R. G., Schulze, A. B., Buhl, R., & Radsak, M. P. (2018) · Scientific Reports · doi:10.1038/s41598-018-28971-0 · Cited by 22

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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