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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BackgroundResultInfluential
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BackgroundInfluential
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Background
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Background
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Maccioni, L., Kasavuli, J., Leclercq, S., Pirlot, B., Laloux, G., Horsmans, Y., Leclercq, I. A., Schnabl, B., & Stärkel, P. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000107 · Cited by 12
“CD9 is highly expressed on monocytes as well as on monocyte-derived macrophages involved in tissue scaring,[25,26] Activated monocytes, especially those secreting IL-8 and MCP-1, do express triggering receptor expressed on myeloid cells 1 (TREM1) which is upregulated by bacterial products such as LPS.[27,28] Furthermo…”
Background
TREM-1 Contributes to Inflammation in IgA Nephropathy
Zhao, Y., Zhu, L., Liu, L., et al. (2018) · Kidney Diseases · doi:10.1159/000485622 · Cited by 11
Association of variants in IL1B, TLR9, TREM1, IL10RA, and CD3G and Native American ancestry on malaria susceptibility in Colombian populations
Mario-Vasquez, J. E., Naranjo-González, C. A., Montiel, J., Zuluaga, L. M., Vásquez, A. M., Tobón-Castaño, A., Bedoya, G., & Segura, C. (2020) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2020.104675 · Cited by 12
CRPMKB: a knowledge base of cancer risk prediction models for systematic comparison and personalized applications
Ren, S., Jin, Y., Chen, Y., & Shen, B. (2021) · Bioinformatics · doi:10.1093/bioinformatics/btab850 · Cited by 11
Increased expression of Dec-205, Bcl-10, Tim-3, and Trem-1 mRNA in chronic otitis media with cholesteatoma
Kim, M. G., Park, D. C., Oh, I., et al. (2014) · Acta Oto-Laryngologica · doi:10.3109/00016489.2013.878474 · Cited by 11
“Trem-1 is up-regulated by bacterial LPS, mediates the activation of neutrophils and monocytes, and plays an important role in the immune response by inducing the secretion of inflammatory chemokines and cytokines and the release of myeloperoxidase, and by up-regulating adhesion molecules [17].”
Background
TREM-1 modulation produces positive outcome on the histopathology and cytokines release profile of Plasmodium berghei-infected mice
Chin, V. K., Asyran, A. M. Y., Zakaria, Z. A., et al. (2018) · Journal of Parasitic Diseases · doi:10.1007/s12639-018-1070-3 · Cited by 11
Role of TREM2 in neuroinflammation
Abdulkhaliq, A. A., Alasiri, G. A., Almoghrabi, Y. M., Kim, B., Khan, J., Ajoolabady, A., Ren, J. T., Tuomilehto, J. O., Borai, A., & Praticò, D. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115547 · Cited by 10
TREM2 in Regulating Macrophage Inflammatory Responses and Disease Pathogenesis
Medd, M. M. (2024) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2024054889 · Cited by 12
RhoA/ROCK/GSK3β Signaling: A Keystone in Understanding Alzheimer’s Disease
Medd, M. M., Yon, J. E., & Dong, H. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47020124 · Cited by 11
“TREMs primarily act as modulators of the immune response that regulate the activation of myeloid cells, notably macrophages [198,199].”
Biomarkers in lower respiratory tract samples in the diagnosis of ventilator-associated pneumonia: a systematic review
Ljungcrantz, E. G., Askman, S., Sjövall, F., & Paulsson, M. (2025) · European Respiratory Review · doi:10.1183/16000617.0229-2024 · Cited by 10
“The soluble form is elevated in cell free body fluids during infection or inflammation and is present in very low concentrations in healthy controls [62, 63].”
Early changes of the kinetics of monocyte trem-1 reflect final outcome in human sepsis
Marioli, A., Koupetori, M., Raftogiannis, M., et al. (2014) · BMC Immunology · doi:10.1186/s12865-014-0063-y · Cited by 10
“The triggering receptor expressed on myeloid cells (TREM-1) is a pattern-recognition receptor expressed on neutrophils and monocytes [6], playing a key-role in the septic process [7].”
Background
Plasma and genetic determinants of soluble TREM-1 and major adverse cardiovascular events in a prospective cohort of acute myocardial infarction patients. Results from the FAST-MI 2010 study
Ait‐Oufella, H., Yu, M., Kotti, S., et al. (2021) · International Journal of Cardiology · doi:10.1016/j.ijcard.2021.09.018 · Cited by 10
Peri-Implant Surgical Treatment Downregulates the Expression of sTREM-1 and MMP-8 in Patients with Peri-Implantitis: A Prospective Study
Neves, G. S. T., Elangovan, G., Teixeira, M. K. S., de Mello‐Neto, J. M., Tadakamadla, S. K., Lourenço, E., Telles, D. D. M., & Figueredo, C. M. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19063627 · Cited by 10
“Cells such as monocytes, macrophages, and neutrophils express TREM-1 during inflammatory and infectious processes [10,11].”
Background
Association of salivary TREM‐1 and PGLYRP1 inflammatory markers with non‐communicable diseases
Silbereisen, A., Lira‐Junior, R., Åkerman, S., et al. (2023) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.13858 · Cited by 10
Antimicrobial peptide LL-37 along with peptidoglycan drive monocyte polarization toward CD14(high)CD16(+) subset and may play a crucial role in the pathogenesis of psoriasis guttata.
Qian, L., Chen, W., Sun, W., et al. (2015) · PubMed · Cited by 10
Gene Dysfunction Mediates Immune Response to Dopaminergic Degeneration in Parkinson’s Disease
Jiao, Z., Zhang, W., Chen, C., Zhu, X., Chen, X., Zhou, M., Peng, G., Liu, H., Qiu, J., Lin, Y., et al. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00373 · Cited by 10
Research and progress on biomarkers of neuromyelitis optica spectrum disorders
Wang, J., Liu, J., Li, R., & Wang, C. (2020) · Journal of Receptors and Signal Transduction · doi:10.1080/10799893.2020.1830109 · Cited by 10
“TREM2 on the membrane of microglia contains three domains: extracellular region, a transmembrane area, and cytoplasmic tail [69].”
Background
TREM-1 enhances Mycobacterium tuberculosis-induced inflammatory responses in macrophages
Feng, J., Su, W., Chuang, F., et al. (2020) · Microbes and Infection · doi:10.1016/j.micinf.2020.10.001 · Cited by 10
Identification of Auxiliary Biomarkers and Description of the Immune Microenvironmental Characteristics in Duchenne Muscular Dystrophy by Bioinformatical Analysis and Experiment
Han, X., Han, J., Wang, N., Ji, G., Guo, R., Li, J., Wu, H., Ma, S., Fang, P., & Song, X. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.891670 · Cited by 10
“The TYROBP gene, also known as DAP12, serves as a downstream adaptor for many immune receptors such as trigger receptor expression myeloid 1 (TREM1) (Bouchon et al., 2000), trigger receptor expression myeloid 2 (TREM2) (Colonna, 2003), and complement receptor 3 (CR3) (Linnartz and Neumann, 2013).”
Background
Mechanistic Role of Jak3 in Obesity-Associated Cognitive Impairments
Kumar, P., Mishra, J., & Kumar, N. (2022) · Nutrients · doi:10.3390/nu14183715 · Cited by 10
“First identified in dendritic cells and macrophages, the triggering receptor expressed on myeloid cells 2 (TREM2) is a single-pass transmembrane receptor on the microglial cells in the brain [84].”
Background
Hypoxic Stress Induced TREM-1 and Inflammatory Chemokines in Human Peripheral Blood Mononuclear Cells
Mishra, K. P., Jain, S. K., Ganju, L., et al. (2013) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-013-0345-9 · Cited by 10
“TREM-1 activation also enhances the production of TNF-a, IL-6, and MIP-2, as well as PMN infiltration [7].”
Background
Molecular Cloning and Expression Pattern of Porcine Myeloid DAP12-Associating Lectin-1
Yim, D., Jie, H.-B., Sotiriadis, J., et al. (2001) · Cellular Immunology · doi:10.1006/cimm.2001.1782 · Cited by 10
Endocrine Markers of Severity and Prognosis in Critical Illness
Nylen, E. S., Seam, N., & Khosla, R. (2006) · Critical Care Clinics · doi:10.1016/j.ccc.2005.08.002 · Cited by 10
Study of different diagnostic markers used to differentiate septic from aseptic meningitis
El-Yamany, S. A., Mayah, W. W., Jiman-Fatani, A. A., Saadany, S. A. E., Hassanien, M. A., Hasan, A., & Abo-Hagar, H. H. (2013) · Journal of Microscopy and Ultrastructure · doi:10.1016/j.jmau.2013.06.007 · Cited by 10
CD Antigens 2001: Aims and Results of HLDA Workshops
Mason, D. Y., André, P., Bensussan, A., et al. (2001) · Stem Cells · doi:10.1634/stemcells.19-6-556 · Cited by 10
Genomic organisation analysis of novel immunoglobulin-like transcripts in Atlantic salmon (Salmo salar) reveals a tightly clustered and multigene family
Østergaard, A. E., Lubieniecki, K. P., Martín, S., et al. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-697 · Cited by 10
“TREM receptors are involved in the amplification and attenuation of the inflammatory response [8,9], while the NKp44 receptor activates NK cells [10].”
Background
Differential expression of immune-related genes between healthy volunteers and type 2 diabetic patients with spleen-deficiency pattern
Longhui, C., Zemin, Y., Weiwen, C., et al. (2015) · 中医杂志：英文版 · doi:10.1016/s0254-6272(15)30154-0 · Cited by 10
Predictive Value of Serial Measurements of sTREM-1 in the Treatment Response of Patients with Community-acquired Pneumonia
Chao, W., Wang, C., Chan, M.-C., et al. (2007) · Journal of the Formosan Medical Association · doi:10.1016/s0929-6646(09)60239-4 · Cited by 10
Immune activation in female infertility: Significance of autoantibodies and inflammatory mediators
Tagoma, A. (2013) · DSpace repository (University of Tartu) · Cited by 10
Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19
Matthay, Z. A., Fields, A. T., Wick, K. D., Jones, C., Lane, H. C., Herrera, K., Nunez‐Garcia, B., Gennatas, E. D., Hendrickson, C. M., Kornblith, A. E., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1130821 · Cited by 9
“TREM-1, a mediator of inflammation and prognostic biomarker in sepsis, was elevated in patients who developed severe disease, though did not achieve statistical significance after adjustment for multiple comparisons (38, 39).”
Background
Neuronal ablation of GHSR mitigates diet-induced depression and memory impairment via AMPK-autophagy signaling-mediated inflammation
Wang, H., Shen, Z., Wu, C., Ji, P., Noh, J. Y., Geoffroy, C. G., Kim, S.-J., Threadgill, D. W., Li, J., Zhou, Y., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1339937 · Cited by 9
Risk of Alzheimer's disease in Down syndrome: Insights gained by multi‐omics
Qu, H., Liu, Y., Connolly, J. J., Mentch, F. D., Kao, C., & Hakonarson, H. H. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14604 · Cited by 9
“185 Therefore, the therapeutic focus may need to prioritize restoring the impaired function of specific TREM2 variants rather than simply enhancing TREM2 activity.”
Charting γ-secretase substrates by explainable AI
Breimann, S., Kamp, F., Basset, G., Abou‐Ajram, C., Güner, G., Yanagida, K., Okochi, M., Müller, S. A., Lichtenthaler, S. F., Langosch, D., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60638-z · Cited by 9
Evaluation and Validation of the Detection of soluble Triggering Receptor Expressed on Myeloid Cells 1 by Enzyme-linked immunosorbent Assay
Hasibeder, A., Stein, P., Brandwijk, R. J. M. G. E., et al. (2015) · Scientific Reports · doi:10.1038/srep15381 · Cited by 9
Evaluation of TREM1 Gene Expression in Circulating Polymorphonuclear Leukocytes and Its Inverse Correlation with the Severity of Pathophysiological Conditions in Patients with Acute Bacterial Infections
Ubagai, T., Tansho, S., Ieki, R., & Ono, Y. (2012) · Japanese Journal of Infectious Diseases · doi:10.7883/yoken.65.376 · Cited by 9
“This receptor has been found to amplify the immune response that strongly potentiates the activation of PMNs in response to microbial products (24).”
Background
Lack of an Association between the Functional Polymorphism TREM-1 rs2234237 and the Clinical Course of Sepsis among Critically Ill Caucasian Patients—A Monocentric Prospective Genetic Association Study
Runzheimer, J., Mewes, C., Büttner, B., Hinz, J. M., Popov, A., Ghadimi, M. B., Kristóf, K., Beißbarth, T., Schamroth, J., Tzvetkov, M. V., et al. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8030301 · Cited by 9
“TREM-1 expression is enhanced by inflammatory stimuli such as lipopolysaccharides (LPS), a ligand for TLR4, or lipoteichoic acids [13,14].”
Background
TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis
Bernal‐Martínez, L., Gonçalves, S. M., de Andrés, B., Cunha, C., González-Jiménez, I., Lagrou, K., Mellado, E., Gaspar, M.-L., Maertens, J., Carvalho, A., et al. (2021) · Virulence · doi:10.1080/21505594.2021.1879471 · Cited by 9
“TREM1 is an immune receptor expressed on innate immune cells, such as neutrophils, mature monocytes, macrophages [9], and platelets [35].”
Background
Effects of avian triggering receptor expressed on myeloid cells (TREM-A1) activation on heterophil functional activities
Kogut, M. H., Genovese, K. J., Nerren, J. R., & He, H. (2011) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2011.06.015 · Cited by 9
“Lastly, we have demonstrated that ligation of TREM-A1 on chicken heterophils leads to the activation of ERK1/2 which is similar to that observed in mammalian neutrophils (Bouchon et al., 2000; Colonna and Facchetti, 2003).”
BackgroundResultInfluential
Dexamethasone Down-Regulates Expression of Triggering Receptor Expressed on Myeloid Cells-1: Evidence for a TNFα-Related Effect
Mihailidou, I., Πελεκάνου, Α., Pistiki, A. C., Spyridaki, A., Tzepi, I., Damoraki, G., & Giamarellos‐Bourboulis, E. J. (2013) · Frontiers in Public Health · doi:10.3389/fpubh.2013.00050 · Cited by 9
Chicken TREM-B1, an Inhibitory Ig-Like Receptor Expressed on Chicken Thrombocytes
Turowski, V., Sperling, B., Hanczaruk, M. A., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151513 · Cited by 9
TREM-1low is a novel characteristic for tumor-associated macrophages in lung cancer
Zhang, G., Liu, H., Huang, J. A., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9639 · Cited by 9
“As previously described, TREM-1 is known as a key molecule for the triggering and amplification of inflammatory response to stimulate proinflammatory cytokines secretion [7, 8].”
BackgroundInfluential
LR12‐peptide quantitation in whole blood by RP‐HPLC and intrinsic fluorescence detection: Validation and pharmacokinetic study
Parent, M., Boudier, A., Maincent, P., et al. (2016) · Biomedical Chromatography · doi:10.1002/bmc.3877 · Cited by 9

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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