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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Bakker, A. B., Hoek, R., Cerwenka, A., Blom, B., Lucian, L., McNeil, T., Murray, R., Phillips, L., Sedgwick, J., & Lanier, L. (2000) · Immunity · doi:10.1016/s1074-7613(00)00034-0 · Cited by 269
Impaired Synaptic Function in the Microglial KARAP/DAP12-Deficient Mouse
Roumier, A., Béchade, C., Poncer, J. C., Smalla, K., Tomasello, E., Vivier, É., Gundelfinger, E. D., Triller, A., & Bessis, A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2251-04.2004 · Cited by 248
“KARAP/DAP12 is expressed in multiple cell types derived from the myeloid lineage (Bouchon et al., 2000), but its presence in microglia was only mentioned as unpublished results (Bakker et al.”
BackgroundResult
TREM-1 Exacerbates Neuroinflammatory Injury via NLRP3 Inflammasome-Mediated Pyroptosis in Experimental Subarachnoid Hemorrhage
Xu, P., Hong, Y., Xie, Y., et al. (2020) · Translational Stroke Research · doi:10.1007/s12975-020-00840-x · Cited by 224
Pattern recognition receptor function in neutrophils
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Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions
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“TREM2 expression was first observed in macrophages and dendritic cells, but not granulocytes or monocytes (Bouchon et al. 2000; Bouchon et al. 2001; Daws et al. 2001).”
Background
TREM2, microglia, and Alzheimer’s disease.
Qin, Q., Teng, Z., Liu, C., Li, Q., Yin, Y., & Tang, Y. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111438 · Cited by 219
TREM-1 ligand expression on platelets enhances neutrophil activation
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TREM-2 promotes macrophage survival and lung disease after respiratory viral infection
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“2, C and D), consistent with the association of TREM-2 and DAP12 phenotype in other systems (Bouchon et al., 2000; Kaifu et al., 2003; Turnbull et al., 2006).”
Background
Triggering Receptor Expressed on Myeloid Cells-1 in Neutrophil Inflammatory Responses: Differential Regulation of Activation and Survival
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“TREM-1 induces rapid degranulation TREM-1 has been shown to induce the release of MPO and IL-8 (17).”
BackgroundResultInfluential
The TREM-1/DAP12 pathway
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BackgroundInfluential
The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function
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PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcRγ to induce slow leukocyte rolling
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Reprint of Neutrophil cell surface receptors and their intracellular signal transduction pathways
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From expression to signaling: Roles of TREM-1 and TREM-2 in innate immunity and bacterial infection
Sharif, O., & Knapp, S. (2008) · Immunobiology · doi:10.1016/j.imbio.2008.07.008 · Cited by 199
“TREM-1 consists of an extracellular domain, a transmembrane region which contains a conserved lysine residue (Ramanathan et al., 2005), and a short cytoplasmic domain, which lacks any signaling motif (Bouchon et al., 2000; Radaev et al., 2003; Kelker et al., ARTICLE IN PRESS”
BackgroundMethodInfluential
The role of platelets in the recruitment of leukocytes during vascular disease
Rainger, G. E., Chimen, M., Harrison, M. J., Yates, C. M., Harrison, P., Watson, S. P., Lordkipanidzé, M., & Nash, G. B. (2015) · Platelets · doi:10.3109/09537104.2015.1064881 · Cited by 197
TREM2 in CNS homeostasis and neurodegenerative disease
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The innate signaling of dangers and the dangers of innate signaling
Sansonetti, P. J. (2006) · Nature Immunology · doi:10.1038/ni1420 · Cited by 185
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Background
Innate Immune Responses to TREM-1 Activation: Overlap, Divergence, and Positive and Negative Cross-Talk with Bacterial Lipopolysaccharide
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“A contributing factor to positive cross-talk with prolonged treatment may be that PRR ligands can up-regulate TREM-1 expression (9, 11, 12, 23, 24).”
Background
The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
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Identification and characterization of SKAT-2, a novel Th2-specific zinc finger gene
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Evolution of effectors and receptors of innate immunity
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Inhibitory ITAMs as novel regulators of immunity
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“Indeed, incubation of these deficient cells with lipopolysaccharide (LPS) or CpG DNA induced higher production of tumor-necrosis factor-a (TNFa), interleukin-6 (IL-6), and IL-12 as compared with wildtype macrophages, suggesting that in wildtype macrophages, a DAP12 signal is required to limit TLR-induced cytokine prod…”
BackgroundInfluential
Inflammatory mediators in major depression and bipolar disorder
Poletti, S., Mazza, M. G., & Benedetti, F. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02921-z · Cited by 195
Ventilator-associated pneumonia: pathobiological heterogeneity and diagnostic challenges
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KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions
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Genetics ignite focus on microglial inflammation in Alzheimer’s disease
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“The R47H variant blunts the TREM2-DAP12 response to anionic lipids [29]; therefore, the mutation may reflect a stage of TREM2 function intermediate between full function and the complete loss of function that is associated with the recessive Nasu-Hakola disease.”
Influential
Novel biomarkers for sepsis: A narrative review
Larsen, F. F., & Petersen, J. A. (2017) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2017.09.030 · Cited by 162
Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity
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Combined Natural Killer Cell and Dendritic Cell Functional Deficiency in KARAP/DAP12 Loss-of-Function Mutant Mice
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Microglial TYROBP/DAP12 in Alzheimer's Disease: Transduction of Physiological and Pathological Signals Across TREM2
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“Of note, while a low level of TREM3 is detected in mouse microglia, TREM3 in humans is present as a pseudogene [56, 70, 106].”
Background
Complex Roles of Microglial Cells in Ischemic Stroke Pathobiology: New Insights and Future Directions
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“Abbreviations BBB, blood–brain barrier; rtPA, recombinant tissue-plasminogen activator; FDA, food and drug administration; ROS, reactive oxygen species; CD, clusters of differentiation; PRRs, pattern recognition receptors; TLRs, toll-like receptors; NLRs, nucleotide-binding oligomerization domain (nod)-like receptors;…”
BackgroundInfluential
Combinations of Host Biomarkers Predict Mortality among Ugandan Children with Severe Malaria: A Retrospective Case-Control Study
Erdman, L. K., Dhabangi, A., Musoke, C., Conroy, A. L., Hawkes, M., Higgins, S. J., Rajwans, N., Wolofsky, K. T., Streiner, D. L., Liles, W. C., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017440 · Cited by 159
“The TREM-1 receptor is expressed on the cell membrane of monocytes and neutrophils and mediates pro-inflammatory responses [37].”
Background

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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