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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Background
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Background
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Background
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Background
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Background
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“Triggering receptor expressed on myeloid cells-1 (TREM-1), a 30-kDa immuno-globulin superfamily member, is a recently discovered cell-surface molecule identified on both human and murine neutrophils and mature monocytes [3, 4].”
Background
Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells
Prüfer, S., Weber, M., Sasca, D., Teschner, D., Wölfel, C., Stein, P., Stassen, M., Schild, H., & Radsak, M. P. (2013) · Journal of Innate Immunity · doi:10.1159/000355892 · Cited by 35
Pig immune response to general stimulus and to porcine reproductive and respiratory syndrome virus infection: a meta-analysis approach
Badaoui, B., Tuggle, C. K., Hu, Z., Reecy, J. M., Aït-Ali, T., Anselmo, A., & Botti, S. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-220 · Cited by 36
“receptor-associated kinase 1 (IRAK1), NF-κB, and the pro-inflammatory response [51,52].”
Background
EFFECTS OF THE TREM 1 PATHWAY MODULATION DURING HEMORRHAGIC SHOCK IN RATS
Gibot, S., Massin, F., Alauzet, C., et al. (2009) · Shock · doi:10.1097/shk.0b013e3181a53842 · Cited by 35
“pressed on neutrophils and monocytes/macrophages and acts as a crucial amplifier of the inflammatory signaling (10, 12, 14).”
BackgroundInfluential
Emerging drugs for the treatment of sepsis
Heming, N., Lamothe, L., Ambrosi, X., & Annane, D. (2006) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2016.1132700 · Cited by 17
CD1c-Expression by Monocytes – Implications for the Use of Commercial CD1c+ Dendritic Cell Isolation Kits
Schrøder, M., Melum, G. R., Landsverk, O. J. B., Bujko, A., Yaqub, S., Gran, E., Aamodt, H., Bækkevold, E. S., Jahnsen, F. L., & Richter, L. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157387 · Cited by 34
“In addition to CD115, CD14+CD1c+ cells, but not CD14-CD1c+, expressed further markers considered strongly and specifically expressed by blood monocytes: chemokine receptor CCR2 [25], integrin alpha M (CD11b) [26], triggering receptor expressed on myeloid cells TREM1 [27,28], as well as calprotectin subunit S100A9 [26,…”
Background
New genetic players in late-onset Alzheimer's disease
Misra, A., Chakrabarti, S. S., & Gambhir, I. S. (2018) · The Indian Journal of Medical Research · doi:10.4103/ijmr.ijmr_473_17 · Cited by 36
TMEM59 interacts with TREM2 and modulates TREM2-dependent microglial activities
Liu, Z., Ning, J., Zheng, X., Meng, J., Han, L., Zheng, H., Zhong, L., Chen, X., Zhang, X., Luo, H., et al. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-02874-3 · Cited by 35
A Comprehensive Summary of the Knowledge on COVID-19 Treatment
Peng, Y., Tao, H., Satyanarayanan, S. K., Jin, K., & Su, H. (2021) · Aging and Disease · doi:10.14336/ad.2020.1124 · Cited by 35
“[201] Pattern recognition receptors [Toll or Toll-like receptors (TLR)] can recognize pathogens (pathogen-related molecular patterns or pathogen-associated molecular pattern (PAMPs) or components of injured cells (risk-related molecular patterns or damage-associated molecular patterns (DAMPs)).”
Background
The Crystal Structure of the Extracellular Domain of the Inhibitor Receptor Expressed on Myeloid Cells IREM-1
Márquez, J. A., Galfrè, E., Dupeux, F., Flot, D. M., Morán, Ó., & Dimasi, N. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.01.011 · Cited by 34
Expression of TREM-1 is inhibited by PGD2 and PGJ2 in macrophages
Syed, M. A., Joo, M., Abbas, Z., Rodger, D., Christman, J. W., Mehta, D., & Sadikot, R. T. (2010) · Experimental Cell Research · doi:10.1016/j.yexcr.2010.08.009 · Cited by 34
OSCAR‐collagen signaling in monocytes plays a proinflammatory role and may contribute to the pathogenesis of rheumatoid arthritis
Schultz, H. S., Guo, L., Keller, P., Fleetwood, A. J., Sun, M., Guo, W., Ma, C., Hamilton, J. A., Björkdahl, O., Berchtold, M. W., et al. (2016) · European Journal of Immunology · doi:10.1002/eji.201545986 · Cited by 35
GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis
Abdel-Aziz, H., Schneider, M. J., Neuhuber, W., et al. (2015) · Molecular Medicine · doi:10.2119/molmed.2015.00098 · Cited by 33
New Agents in Development for Sepsis: Any Reason for Hope?
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Hsp70 Interacts with the TREM-1 Receptor Expressed on Monocytes and Thereby Stimulates Generation of Cytotoxic Lymphocytes Active against MHC-Negative Tumor Cells
Sharapova, T. N., Romanova, E. A., Ivanova, O. K., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136889 · Cited by 33
“A family of the Triggering Receptors Expressed on Myeloid cells (TREMs) was described in 2000 [3], they play an important role in the modulation of immune response.”
Background
Microglial TREM2 in amyotrophic lateral sclerosis
Xie, M., Zhao, S., Bosco, D. B., Nguyen, A. T., & Wu, L. (2021) · Developmental Neurobiology · doi:10.1002/dneu.22864 · Cited by 35
Variant TREM2 Signaling in Alzheimer's Disease
Olufunmilayo, E. O., & Holsinger, R. M. D. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167470 · Cited by 33
TLR4-Pathway-Associated Biomarkers in Subarachnoid Hemorrhage (SAH): Potential Targets for Future Anti-Inflammatory Therapies
Heinz, R., & Schneider, U. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012618 · Cited by 33
“Discovered in 2000 [57], the family increased from only one (TREM-1) to three receptors, all of which have slightly different tasks.”
Background
Human Natural Killer Receptors and Their Ligands
Biassoni, R., Bottino, C., Cantoni, C., & Moretta, A. (2001) · Current Protocols in Immunology · doi:10.1002/0471142735.im1410s46 · Cited by 33
“Interestingly, TREM-1 and TREM-2 genes code for receptors that a lso associate with KARAP/DAP12 molecules, but that are expressed by neutrophils and monocytes or macrophages and dendritic cells, respectively (Bouchon et al., 2000).”
Background
The Increased Expression of TREM-1 on Monocytes Is Associated With Infectious and Noninfectious Inflammatory Processes
Ferat-Osorio, E. A., Esquivel-Callejas, N., Wong‐Baeza, I., et al. (2008) · Journal of Surgical Research · doi:10.1016/j.jss.2007.12.805 · Cited by 33
“In psoriasis, ulcerative colitis, and vasculitis, which are noninfectious inflammatory processes, TREM-1 expression is not increased [9, 10].”
Background
Triggering Receptor Expressed on Myeloid Cell 1
Barraud, D., & Gibot, S. (2011) · Critical Care Clinics · doi:10.1016/j.ccc.2010.12.006 · Cited by 33
The Linker for Activation of B Cells (LAB)/Non-T Cell Activation Linker (NTAL) Regulates Triggering Receptor Expressed on Myeloid Cells (TREM)-2 Signaling and Macrophage Inflammatory Responses Independently of the Linker for Activation of T Cells
Whittaker, G. C., Orr, S. J., Quigley, L., Hughes, L., Francischetti, I. M. B., Zhang, W., & McVicar, D. W. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.038398 · Cited by 33
Effect of TREM-1 blockade and single nucleotide variants in experimental renal injury and kidney transplantation
Tammaro, A., Kers, J., Emal, D., Stroo, I., Teske, G. J. D., Butter, L. M., Claessen, N., Damman, J. J., Derive, M., Navis, G. J., et al. (2016) · Scientific Reports · doi:10.1038/srep38275 · Cited by 33
TREM2: Keeping Pace With Immune Checkpoint Inhibitors in Cancer Immunotherapy
Qiu, H., Shao, Z., Wen, X., Jiang, J., Ma, Q., Wang, Y., Huang, L., Ding, X., & Zhang, L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.716710 · Cited by 32
The role of TREM2 N-glycans in trafficking to the cell surface and signal transduction of TREM2
Shirotani, K., Hatta, D., Wakita, N., Watanabe, K., & Iwata, N. (2022) · The Journal of Biochemistry · doi:10.1093/jb/mvac073 · Cited by 31
Regulation of TREM-1 expression by 1,25-dihydroxyvitamin D3 in human monocytes/macrophages
Kim, T., Lee, B., Kwon, E., et al. (2013) · Immunology Letters · doi:10.1016/j.imlet.2013.08.012 · Cited by 32
Serum Soluble Triggering Receptor on Myeloid Cells-1 (sTREM-1) is Elevated in Systemic Lupus Erythematosus but does not Distinguish Between Lupus Alone and Concurrent Infection
Molad, Y., Pokroy‐Shapira, E., Kaptzan, T., et al. (2013) · Inflammation · doi:10.1007/s10753-013-9694-z · Cited by 32
RETRACTED ARTICLE: TREM-1 associated macrophage polarization plays a significant role in inducing insulin resistance in obese population
Subramanian, S., Pallati, P. K., Sharma, P., Agrawal, D. K., & Nandipati, K. C. (2017) · Journal of Translational Medicine · doi:10.1186/s12967-017-1187-7 · Cited by 32
“It is expressed mostly on myeloid cells (monocytes, macrophages and neutrophils) and recognized as a potent amplifier of acute and chronic inflammation [18].”
Background
Retracted
Diagnostic value of serum soluble triggering expressed receptor on myeloid cells 1 (sTREM-1) in suspected sepsis: a meta-analysis
Chang, W., Peng, F., Meng, S., Xu, J., & Yang, Y. (2020) · BMC Immunology · doi:10.1186/s12865-020-0332-x · Cited by 34
Heat shock protein is a key therapeutic target for nerve repair in autoimmune peripheral neuropathy and severe peripheral nerve injury
Asthana, P., Zhang, G., Sheikh, K. A., & Ma, C. H. E. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.08.020 · Cited by 32
BRD4 inhibition alleviates mechanical stress-induced TMJ OA-like pathological changes and attenuates TREM1-mediated inflammatory response
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Evaluation of a new inflammatory molecule (triggering receptor expressed on myeloid cells‐1) in the diagnosis of pleural effusion
Chan, M.-C., CHANG, K., Chao, W., et al. (2007) · Respirology · doi:10.1111/j.1440-1843.2007.01056.x · Cited by 32
An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD
Brynjolfsson, S. F., Magnusson, M. K., Kong, P. L., Jensen, T., Kuijper, J. L., Håkansson, K., Read, C. B., Stennicke, V. W., Sjövall, H., & Wick, M. J. (2016) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000822 · Cited by 32
Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome
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Triggering Receptor Expressed on Myeloid cells-1: a new player in platelet aggregation
Jolly, L., Lemarie, J., Carrasco, K., et al. (2017) · Thrombosis and Haemostasis · doi:10.1160/th17-03-0156 · Cited by 32
“The Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is an immune-receptor expressed by human and murine neutrophils, mature monocytes and macrophages that acts as an amplifier of the innate immune response (10, 11).”
Background
Increased serum TREM-1 level is associated with in-stent restenosis, and activation of TREM-1 promotes inflammation, proliferation and migration in vascular smooth muscle cells
Wang, F., Li, C., Ding, F. H., et al. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.10.015 · Cited by 32
“Triggering receptor expressed on myeloid cells (TREM)-1 is a ~26 kDa transmembrane glycoprotein of the immunoglobulin superfamily [16,17], initially identified on neutrophils and monocytes [16].”
Background
Triggering Receptor Expressed on Myeloid Cells-1 Inhibitor Targeted to Endothelium Decreases Cell Activation
Gibot, S., Jolly, L., Lemarie, J., Carrasco, K., Derive, M., & Boufenzer, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02314 · Cited by 31
Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism
Lim, C. L., Or, Y. Z., Ong, Z., Chung, H. H., Hayashi, H., Shrestha, S., Chiba, S., Lin, F., & Lin, V. C. L. (2020) · eLife · doi:10.7554/elife.57274 · Cited by 31
Extracellular CIRP Induces Inflammation in Alveolar Type II Cells via TREM-1
Tan, C., Gurien, S. D., Royster, W., Aziz, M., & Wang, P. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.579157 · Cited by 31
TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn’s Disease Patients
Caër, C., Gorreja, F., Forsskåhl, S. K., Brynjolfsson, S. F., Szeponik, L., Magnusson, M. K., Börjesson, L. G., Block, M., Lindskog, E. B., & Wick, M. J. (2021) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjab022 · Cited by 33
“Number of patients 26 39 15 Percentage of females 50 56 20 Age in years, median [range] 73 [22–94] 42 [17–79] 39 [24–58] Disease duration in years, median [range] 13 [0–39] 12 [3–33] Harvey–Bradshaw index, median [range] 8 [0–24] Full Mayo score, median [range] 3 [0–9] Disease status, active inflammation/remission 33/…”
Elevated serum TREM-1 is associated with periodontitis and disease activity in rheumatoid arthritis
İnanç, N., Mumcu, G., Can, M., Yay, M., Silbereisen, A., Manoil, D., Direskeneli, H., & Bostancı, N. (2021) · Scientific Reports · doi:10.1038/s41598-021-82335-9 · Cited by 33
Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways
PRINS, M., Verstockt, B., Ferrante, M., Vermeire, S., Wildenberg, M. E., & Koelink, P. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.627535 · Cited by 31

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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