Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes
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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TREM2 expression was first observed in macrophages and dendritic cells, but not granulocytes or monocytes.
“TREM2 expression was first observed in macrophages and dendritic cells, but not granulocytes or monocytes (9–11).”
From <i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [9]
Cites
Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm
Springer, T. A. (1994) · Cell · doi:10.1016/0092-8674(94)90337-9 · Cited by 7,009 · see citing works
Lanier, L. L. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.359 · Cited by 1,646 · see citing works
Recognition of Gram-negative bacteria and endotoxin by the innate immune system
Ulevitch, R. J., & Tobias, P. S. (1999) · Current Opinion in Immunology · doi:10.1016/s0952-7915(99)80004-1 · Cited by 567 · see citing works
Cantoni, C., Bottino, C., Vitale, M., Pessino, A. M., Augugliaro, R., Malaspina, A., Parolini, S., Moretta, L., Moretta, A., & Biassoni, R. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.5.787 · Cited by 450 · see citing works
Cella, M., Döhring, C., Samaridis, J., Dessing, M., Brockhaus, M., Lanzavecchia, A., & Colonna, M. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.10.1743 · Cited by 430 · see citing works
Bakker, A. B. H., Baker, E. G., Sutherland, G. R., Phillips, J. H., & Lanier, L. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.17.9792 · Cited by 210 · see citing works
Nakajima, H., Samaridis, J., Ångman, L., & Colonna, M. (1999) · PubMed · Cited by 173 · see citing works
Dietrich, J., Cella, M., Seiffert, M., Bühring, H., & Colonna, M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.1.9 · Cited by 172 · see citing works
Nakajima, H., Samaridis, J., Ångman, L., & Colonna, M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.1.5 · Cited by 152 · see citing works
Kubagawa, H., Chen, C., Ho, L. H., Shimada, T., Gartland, L., Mashburn, C. B., Uehara, T., Ravetch, J. V., & Cooper, M. D. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.2.309 · Cited by 148 · see citing works
Myeloma based expression system for production of large mammalian proteins
Traunecker, A. (1991) · Trends in biotechnology · doi:10.1016/0167-7799(91)90038-j · Cited by 95 · see citing works
Intracellular signaling in neutrophil priming and activation
Downey, G. P., Fukushima, T., Fialkow, L., & Waddell, T. K. (1995) · Seminars in Cell Biology · doi:10.1016/s1043-4682(05)80005-4 · Cited by 93 · see citing works
Inhibitory and Stimulatory Functions of Paired Ig-Like Receptor (PIR) Family in RBL-2H3 Cells
Yamashita, Y., Ono, M., & Takai, T. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.8.4042 · Cited by 78 · see citing works
Flagged first, then by citations
Research works printed but not linked: 13
- 1999, Curr. Opin. Immunol., 19
- 1995, Semin. Cell Biol., 345
- 1999, J. Immunol., 5
- 1998, J. Immunol., 4042
- 1999, J. Exp. Med., 309
- 2000, J. Immunol., 9
- 1999, Proc. Natl. Acad. Sci. USA, 9792
- 1998, Annu. Rev. Immunol., 359
- 1999, J. Exp. Med., 787
- 1991, Trends Biotechnol., 109
- 1997, J. Exp. Med., 1743
- 1997, The Leukocyte Antigen Facts Book
- 1994, Cell, 301
Cited by
Sorted by citations
Kalil, A. C., Metersky, M. L., Klompas, M., Muscedere, J., Sweeney, D. A., Palmer, L. B., Napolitano, L. M., O'Grady, N. P., Bartlett, J. G., Carratalà, J., et al. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/ciw353 · Cited by 3,892 · see citing works
“TREM-1 is a member of the immunoglobulin superfamily that has been shown to be strongly expressed on the neutrophils and monocytes infiltrating tissues invaded by bacteria or fungi [107].”
The immunopathogenesis of sepsis
Cohen, J. (2002) · Nature · doi:10.1038/nature01326 · Cited by 2,742 · see citing works
Variant of <i>TREM2</i> Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558 · see citing works
DAMP-sensing receptors in sterile inflammation and inflammatory diseases
Gong, T., Liu, L., Jiang, W., & Zhou, R. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0215-7 · Cited by 1,672 · see citing works
Neutrophils, from marrow to microbes.
Borregaard, N. (2010) · Immunity · doi:10.1016/j.immuni.2010.11.011 · Cited by 1,550 · see citing works
“…cells (TREM-1) (by ligands not yet identified; Ford and McVicar, 2009), which is upregulated (Bouchon et al., 2000, 2001) and signals through DAP12 (presented earlier) (Bouchon et al., 2000; Tessarz and Cerwenka, 2008), may lead to degranulation and transcriptional activity (Bouchon et al., 2000).”
BackgroundTREM-1 amplifies inflammation and is a crucial mediator of septic shock
Bouchon, A., Facchetti, F., Weigand, M. A., & Colonna, M. (2001) · Nature · doi:10.1038/35074114 · Cited by 1,092 · see citing works
TREM2 — a key player in microglial biology and Alzheimer disease
Ulland, T. K., & Colonna, M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0072-1 · Cited by 735 · see citing works
Self-citationComparison of gene expression profiles between human and mouse monocyte subsets
Ingersoll, M. A., Spanbroek, R., Lottaz, C., Gautier, E. L., Frankenberger, M., Hoffmann, R. F. G., Lang, R., Haniffa, M. A., Collin, M. P., Tacke, F., et al. (2009) · Blood · doi:10.1182/blood-2009-07-235028 · Cited by 731 · see citing works
TREMs in the immune system and beyond
Colonna, M. (2003) · Nature Reviews Immunology · doi:10.1038/nri1106 · Cited by 701 · see citing works
Self-citationPaloneva, J., Manninen, T., Christman, G., Hovanes, K., Mandelin, J., Adolfsson, R., Bianchin, M., Bird, T., Miranda, R., Salmaggi, A., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342259 · Cited by 683 · see citing works
“2001a), whereas TREM2 is expressed on macrophages and monocyte-derived dendritic cells, suggesting that TREM2 plays a role in chronic, rather than in acute, inflammation (Bouchon et al. 2000).”
BackgroundInfluentialNeutrophils in development of multiple organ failure in sepsis
Brown, K., Brain, S. D., Pearson, J. D., Edgeworth, J. D., Sm, L., & Treacher, D. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69005-3 · Cited by 652 · see citing works
Soluble Triggering Receptor Expressed on Myeloid Cells and the Diagnosis of Pneumonia
Gibot, S., Cravoisy, A., Lévy, B., Béné, M. C., Faure, G. C., & Bollaert, P. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031544 · Cited by 640 · see citing works
Neutrophil cell surface receptors and their intracellular signal transduction pathways
Futosi, K., Fodor, S., & Mócsai, A. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.06.034 · Cited by 642 · see citing works
“Those include DAP12and FcRγ-associated receptors such as TREM-1 [226,227] and OSCAR [228]; the Neisseria recognition receptor CEACAM3 [229,230]; as well as scavenger receptors, complement receptors and various intracellular lipid-sensing receptors.”
BackgroundThe role of platelets in inflammation
Storey, R. F., & Thomas, M. (2015) · Thrombosis and Haemostasis · doi:10.1160/th14-12-1067 · Cited by 614 · see citing works
“Mediates leukocyte activation and engagement of leukocyte TREM1 induces secretion of IL-8, TNFα and CCL2 (125) Presents IL-1β (126), RANTES (26) to the endothelium.”
BackgroundInfluentialThe TREM receptor family and signal integration
Klesney‐Tait, J., Turnbull, I. R., & Colonna, M. (2006) · Nature Immunology · doi:10.1038/ni1411 · Cited by 586 · see citing works
New insights into the role of TREM2 in Alzheimer’s disease
Gratuze, M., Leyns, C. E. G., & Holtzman, D. M. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0298-9 · Cited by 489 · see citing works
New Approaches to Sepsis: Molecular Diagnostics and Biomarkers
Reinhart, K., Bauer, M. W., Riedemann, N. C., & Hartog, C. S. (2012) · Clinical Microbiology Reviews · doi:10.1128/cmr.00016-12 · Cited by 528 · see citing works
“Studies have shown that the expression of TREM-1 is greatly upregulated in the presence of bacteria or fungi in cell culture, peritoneal lavage fluid, and tissue samples from patients infected with these microorganisms (36, 63).”
BackgroundOxidative stress and gene expression in sepsis
Macdonald, J., Galley, H. F., & Webster, N. R. (2003) · British Journal of Anaesthesia · doi:10.1093/bja/aeg034 · Cited by 497 · see citing works
Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease
Kaur, D., Sharma, V., & Deshmukh, R. R. (2019) · Inflammopharmacology · doi:10.1007/s10787-019-00580-x · Cited by 493 · see citing works
Bouchon, A., Hernández-Munain, C., Cella, M., & Colonna, M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.8.1111 · Cited by 460 · see citing works
“TREM-1 is preferentially expressed on neutrophils and a subset of blood monocytes (53).”
BackgroundResultInfluentialGibot, S., Kolopp‐Sarda, M., Béné, M. C., Cravoisy, A., Lévy, B., Faure, G. C., & Bollaert, P. (2004) · Annals of Internal Medicine · doi:10.7326/0003-4819-141-1-200407060-00009 · Cited by 403 · see citing works
“The triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily, and its expression is upregulated on phagocytic cells in the presence of bacteria or fungi (12).”
Impact of vitamin D on immune function: lessons learned from genome-wide analysis
Chun, R. F., Liu, P. T., Modlin, R. L., Adams, J. S., & Hewison, M. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00151 · Cited by 403 · see citing works
“The increasing availability of gene/protein expression databases for different cell types means that this type of strategy is likely to become a more prominent feature of genome-wide expression analyses in the future.”
BackgroundColonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394 · see citing works
Self-citationGuerreiro, R. J., Lohmann, E., Brás, J. M., Gibbs, J. R., Rohrer, J. D., Gurunlian, N., Dursun, B., Bilgic, B., Hanagasi, H., Gurvit, H., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.579 · Cited by 374 · see citing works
“It may be involved in chronic inflammation by triggering the production of constitutive rather than inflammatory chemokines and cytokines.(22) Interestingly, mutations in both these genes have been associated with PLOSL or Nasu-Hakola disease.”
Chen, S., Peng, J.-H., Sherchan, P., Ma, Y.-J., Xiang, S., Yan, F., Zhao, H., Jiang, Y., Wang, N., Zhang, J. H., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01853-x · Cited by 352 · see citing works
“It contains an ectodomain, a transmembrane domain, and a short cytoplasmic tail [13].”
Schenk, M., Bouchon, A., Seibold, F., & Mueller, C. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30602 · Cited by 365 · see citing works
Soluble TREM2 induces inflammatory responses and enhances microglial survival
Zhong, L., Chen, X., Wang, T., Wang, Z., Liao, C., Wang, Z., Huang, R., Wang, D., Li, X., Wu, L., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20160844 · Cited by 358 · see citing works
“20160844 597 IntroductIon TREM2 is a member of the Ig superfamily that contains an ectodomain, a transmembrane domain, and a short cytoplasmic tail (Bouchon et al., 2000).”
Gibot, S., Kolopp‐Sarda, M., Béné, M.-C., Bollaert, P., Lozniewski, A., Mory, F., Lévy, B., & Faure, G. C. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040708 · Cited by 361 · see citing works
Schmid, C. D., Sautkulis, L. N., Danielson, P. E., Cooper, J., Hasel, K. W., Hilbush, B. S., Sutcliffe, J. G., & Carson, M. J. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01243.x · Cited by 351 · see citing works
“killer cells, T cells or granulocytes (Bouchon et al. 2000; Bouchon et al. 2001; Daws et al. 2001).”
BackgroundInfluentialImmune Signaling in Neurodegeneration
Hammond, T. R., Marsh, S. E., & Stevens, B. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.016 · Cited by 336 · see citing works
“It was first cloned in 2000 by Marco Colonna and colleagues (Bouchon et al., 2000) and is part of a series of Trem and Trem-like genes on human chromosome 6 (mouse chr.”
BackgroundOn guard—activating NK cell receptors
Lanier, L. L. (2001) · Nature Immunology · doi:10.1038/83130 · Cited by 346 · see citing works
Bleharski, J. R., Kiessler, V., Buonsanti, C., Sieling, P. A., Stenger, S., Colonna, M., & Modlin, R. L. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.7.3812 · Cited by 346 · see citing works
“To activate monocytes through TREM-1, an agonist anti-TREM-1 mAb (clone 9E2, mouse IgG1) was generated and purified as described elsewhere (10, 15).”
BackgroundMethodInfluentialElucidating the Role of TREM2 in Alzheimer’s Disease
Ulrich, J. D., Ulland, T. K., Colonna, M., & Holtzman, D. M. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.042 · Cited by 325 · see citing works
“TREM2 associates with the signaling adaptor protein DAP12 through an electrostatic interaction between a conserved lysine in TREM2 and aspartic acid in DAP12 within the transmembrane region (Figure 1) (Bouchon et al., 2000).”
BackgroundNeutrophil dysregulation during sepsis: an overview and update
Shen, X., Cao, K., Jiang, J., Guan, W., & Du, J. (2017) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13112 · Cited by 330 · see citing works
Coding variants in TREM2 increase risk for Alzheimer's disease
Jin, S. C., Benitez, B. A., Karch, C. M., Cooper, B., Skorupa, T., Carrell, D., Norton, J. B., Hsu, S., Harari, O., Cai, Y., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu277 · Cited by 314 · see citing works
“TREM2 is a Type I transmembrane receptor protein expressed on myeloid cells including microglia, monocyte-derived dendritic cells, osteoclasts and bone-marrow derived macrophages (31,32).”
BackgroundDAP10‐ and DAP12‐associated receptors in innate immunity
Lanier, L. L. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00720.x · Cited by 323 · see citing works
The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E
Bailey, C. C., DeVaux, L. B., & Farzan, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.677286 · Cited by 303 · see citing works
“Triggering receptor expressed on myeloid cells 2 (TREM2)(2) is a type I transmembrane protein with a single, extracellular, Ig-like V-type domain (1, 2).”
BackgroundDAP12/TREM2 deficiency results in impaired osteoclast differentiation and osteoporotic features
Paloneva, J., Mandelin, J., Kiialainen, A., Böhling, T., Prudlo, J., Hakola, P., Haltia, M., Konttinen, Y. T., & Peltonen, L. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030027 · Cited by 318 · see citing works
“On the cell membrane of monocyte-derived dendritic cells, DAP12 is expressed as a complex with TREM2 (8, 9).”
BackgroundEnhanced Toll-like receptor responses in the absence of signaling adaptor DAP12
Hamerman, J. A., Tchao, N. K., Lowell, C. A., & Lanier, L. L. (2005) · Nature Immunology · doi:10.1038/ni1204 · Cited by 318 · see citing works
Immune cells: free radicals and antioxidants in sepsis
Víctor, V. M., Rocha, M., & la Fuente, M. D. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.01.020 · Cited by 310 · see citing works
Wunderlich, P., Glebov, K., Kemmerling, N., Tien, N. T., Neumann, H., & Walter, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.517540 · Cited by 296 · see citing works
Semple, J. W., & Freedman, J. J. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0205-1 · Cited by 306 · see citing works
“TREM-1 is a member of the v-type immunoglobulin super family and is expressed on neutrophils and monocytes [116].”
BackgroundPattern Recognition by TREM-2: Binding of Anionic Ligands
Daws, M. R., Sullam, P. M., Niemi, E. C., Chen, T. T., Tchao, N. K., & Seaman, W. E. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.2.594 · Cited by 291 · see citing works
“Three members of the mouse TREM family have been studied: TREM-1 (1, 4), TREM-2 (3, 5), and TREM-3 (2).”
BackgroundMethodInfluentialvan Gils, J. M., Zwaginga, J. J., & Hordijk, P. L. (2008) · Journal of Leukocyte Biology · doi:10.1189/jlb.0708400 · Cited by 298 · see citing works
“Similarly, engagement of CD40 with CD40L, but also TREM-1 ligation, results in an increase in monocyte adhesive capacity by up-regulation of 1- and 2-integrins [54, 77].”
BackgroundInfluentialMicroglial TREM2/DAP12 signaling: a double-edged sword in neural diseases
Konishi, H., & Kiyama, H. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00206 · Cited by 300 · see citing works
Blockade of TREM‐2 exacerbates experimental autoimmune encephalomyelitis
Piccio, L., Buonsanti, C., Mariani, M., Cella, M., Gilfillan, S., Cross, A. H., Colonna, M., & Panina‐Bordignon, P. (2007) · European Journal of Immunology · doi:10.1002/eji.200636837 · Cited by 284 · see citing works
Self-citationGlial activation and inflammation along the Alzheimer’s disease continuum
Nordengen, K., Kirsebom, B.-E., Henjum, K., Selnes, P., Gísladóttir, B., Wettergreen, M., Torsetnes, S. B., Grøntvedt, G. R., Waterloo, K. K., Aarsland, D., et al. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1399-2 · Cited by 274 · see citing works
Colonna, M., & Facchetti, F. (2003) · The Journal of Infectious Diseases · doi:10.1086/374754 · Cited by 281 · see citing works
“TREM-1 is expressed at late stages of myeloid cell differentiation [25] and associates with DAP12 for signaling and function [21].”
BackgroundMethodInfluentialRaggi, F., Pelassa, S., Pierobon, D., Penco, F., Gattorno, M., Novelli, F., Eva, A., Varesio, L., Giovarelli, M., & Bosco, M. C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01097 · Cited by 282 · see citing works
Xu, P., Zhang, X., Liu, Q., Xie, Y., Shi, X., Chen, J., Li, Y., Guo, H., Sun, R., Hong, Y., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1777-9 · Cited by 272 · see citing works
Wang, X., He, Q., Zhou, C., Xu, Y., Liu, D., Fujiwara, N., Kubota, N., Click, A., Henderson, P., Vancil, J., et al. (2023) · Immunity · doi:10.1016/j.immuni.2022.11.013 · Cited by 262 · see citing works
Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction
Welte, S., Kuttruff, S., Waldhauer, I., & Steinle, A. (2006) · Nature Immunology · doi:10.1038/ni1402 · Cited by 259 · see citing works
Microglia and Aging: The Role of the TREM2–DAP12 and CX3CL1-CX3CR1 Axes
Mecca, C., Giambanco, I., Donato, R., & Arcuri, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19010318 · Cited by 259 · see citing works
“TREM2 is a member of the Triggering Receptor Expressed on Myeloid Cells transmembrane glycoproteins, which belongs to the single immunoglobulin variable (IgV) domain receptor family [46].”
BackgroundKlünemann, H. H., Ridha, B. H., Magy, L., Wherrett, J. R., Hemelsoet, D. M., Keen, R. W., De Bleecker, J. L., Rossor, M. N., Marienhagen, J., Klein, H. E., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000160304.00003.ca · Cited by 254 · see citing works
Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation
Mandel, J., Casari, M., Stepanyan, M. G., Martyanov, A. A., & Deppermann, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073868 · Cited by 267 · see citing works
“Platelets and monocytes also come in contact through CD40L–CD40 [182] interactions and monocytetriggering receptors expressed on myeloid cell 1 (TREM-1) to TLT-1 on platelets [183,184].”
BackgroundTREM-1 and its potential ligands in non-infectious diseases: from biology to clinical perspectives
Tammaro, A., Derive, M., Gibot, S., Leemans, J. C., Florquin, S., & Dessing, M. C. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.043 · Cited by 252 · see citing works
The Role of Macrophages and Dendritic Cells in the Initiation of Inflammation in IBD
Steinbach, E. C., & Plevy, S. E. (2013) · Inflammatory Bowel Diseases · doi:10.1097/mib.0b013e3182a69dca · Cited by 250 · see citing works
“Conversely, triggering receptor expressed on myeloid cells-1 (TREM-1) amplifies TLR-induced inflammatory responses in macrophages, and blocking its activity attenuates murine colitis.(100,101) Indeed, resident LP macrophages do not express TREM-1, but abundant TREM-1–expressing LP macrophages can be found in patients…”
BackgroundInnate and adaptive immunity: specificities and signaling hierarchies revisited
Vivier, É., & MALISSEN, B. (2004) · Nature Immunology · doi:10.1038/ni1153 · Cited by 246 · see citing works
Activating and inhibitory functions of DAP12
Turnbull, I. R., & Colonna, M. (2007) · Nature Reviews Immunology · doi:10.1038/nri2014 · Cited by 273 · see citing works
Role of ITAM‐containing adapter proteins and their receptors in the immune system and bone
Humphrey, M. B., Lanier, L. L., & Nakamura, M. C. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00325.x · Cited by 241 · see citing works
“DAP12-deficient mice were more susceptible to endotoxic shock in a galactosamine sensitized LPS model and demonstrated enhanced resistance to infection by Listeria monocytogenes (71).”
BackgroundInfluentialGibot, S., Cravoisy, A., Kolopp‐Sarda, M., Béné, M. C., Faure, G. C., Bollaert, P., & Lévy, B. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000159089.16462.4a · Cited by 230 · see citing works
TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors
Arts, R. J. W., Joosten, L. A. B., van der Meer, J. W. M., & Netea, M. G. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0312145 · Cited by 234 · see citing works
“First, NTAL represses the TREM-1-induced phosphorylation of ERK and the production of TNF- and IL-8, by binding Grb2 and Sos1, which results in less activity of the RAS pathway [1, 39, 42].”
BackgroundDAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming.
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 · see citing works
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 228 · see citing works
“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.”
BackgroundResultXu, P., Hong, Y., Xie, Y., et al. (2020) · Translational Stroke Research · doi:10.1007/s12975-020-00840-x · Cited by 224 · see citing works
Pattern recognition receptor function in neutrophils
Thomas, C. J., & Schroder, K. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.02.008 · Cited by 220 · see citing works
Securing the immune tightrope: mononuclear phagocytes in the intestinal lamina propria
Varol, C., Zigmond, E., & Jung, S. (2010) · Nature reviews. Immunology · doi:10.1038/nri2778 · Cited by 208 · see citing works
Liu, W., Taso, O., Wang, R., Bayram, S., Graham, A. C., Garcia-Reitboeck, P., Mallach, A., Andrews, W. D., Piers, T. M., Botia, J. A., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa209 · Cited by 214 · see citing works
“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).”
BackgroundTREM2, 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 · see citing works
TREM-1 ligand expression on platelets enhances neutrophil activation
Haselmayer, P., Große‐Hovest, L., von Landenberg, P., Schild, H., & Radsak, M. P. (2007) · Blood · doi:10.1182/blood-2007-01-069195 · Cited by 211 · see citing works
TREM-2 promotes macrophage survival and lung disease after respiratory viral infection
Wu, K., Byers, D. E., Jin, X., Agapov, E., Alexander-Brett, J., Patel, A. C., Cella, M., Gilfilan, S., Colonna, M., Kober, D. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20141732 · Cited by 207 · see citing works
“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).”
BackgroundRadsak, M. P., Salih, H. R., Rammensee, H., & Schild, H. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.8.4956 · Cited by 205 · see citing works
“TREM-1 induces rapid degranulation TREM-1 has been shown to induce the release of MPO and IL-8 (17).”
BackgroundResultInfluentialTessarz, A. S., & Cerwenka, A. (2008) · Immunology Letters · doi:10.1016/j.imlet.2007.11.021 · Cited by 202 · see citing works
Metalloproteinases Shed TREM-1 Ectodomain from Lipopolysaccharide-Stimulated Human Monocytes1
Gómez-Piña, V., Soares-Schanoski, A., Rodríguez-Rojas, A., del Fresno, C., García, F., Vallejo-Cremades, M. T., Fernández-Ruíz, I., Arnalich, F., Fuentes-Prior, P., & López-Collazo, E. (2007) · Journal of Immunology · doi:10.4049/jimmunol.179.6.4065 · Cited by 208 · see citing works
“However, only a single band of 900 bases corresponding to the previously described TREM-1 mRNA (1, 7, 23, 24) was detected in our cultures of human monocytes treated with LPS for indicated times.”
BackgroundInfluentialThe ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function
Lanier, L. L., & Bakker, A. B. H. (2000) · Immunology Today · doi:10.1016/s0167-5699(00)01745-x · Cited by 203 · see citing works
Zarbock, A., Abram, C. L., Hundt, M., Altman, A., Lowell, C. A., & Ley, K. F. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20072660 · Cited by 198 · see citing works
Reprint of Neutrophil cell surface receptors and their intracellular signal transduction pathways
Futosi, K., Fodor, S., & Mócsai, A. (2013) · International Immunopharmacology · doi:10.1016/j.intimp.2013.11.010 · Cited by 197 · see citing works
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 196 · see citing works
“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”
BackgroundMethodInfluentialThe 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 193 · see citing works
TREM2 in CNS homeostasis and neurodegenerative disease
Painter, M. M., Atagi, Y., Liu, C.-C., Rademakers, R., Xu, H., Fryer, J. D., & Bu, G. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0040-9 · Cited by 169 · see citing works
“It contains an extracellular domain, a transmembrane domain, and a short cytoplasmic tail [26].”
BackgroundThe innate signaling of dangers and the dangers of innate signaling
Sansonetti, P. (2006) · Nature Immunology · doi:10.1038/ni1420 · Cited by 196 · see citing works
The mucosal immune system at the gastrointestinal barrier
Schenk, M., & Mueller, C. (2008) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2007.11.002 · Cited by 180 · see citing works
Elmezayen, R., Gazzar, M. E., Seeds, M. C., McCall, C. E., Dreskin, S. C., & Nicolls, M. R. (2007) · Immunology Letters · doi:10.1016/j.imlet.2007.04.011 · Cited by 178 · see citing works
“TREM-1 has been shown to synergize with TLRs to amplify the inflammatory response initiated by LPS [24] and induces TNF-α and IL-8 production [23].”
BackgroundDower, K., Ellis, D. K., Saraf, K. A., Jelinsky, S. A., & Lin, L. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.3520 · Cited by 175 · see citing works
“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).”
BackgroundThe Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
Petes, C., Odoardi, N., & Gee, K. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01075 · Cited by 177 · see citing works
Allcock, R. J. N., Barrow, A. D., Forbes, S. A., Beck, S., & Trowsdale, J. (2003) · European Journal of Immunology · doi:10.1002/immu.200310033 · Cited by 173 · see citing works
Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44
Fuchs, A. G., Cella, M., Kondo, T., & Colonna, M. (2005) · Blood · doi:10.1182/blood-2004-12-4802 · Cited by 171 · see citing works
Activation induces rapid and profound alterations in the trafficking of T cells
Hamann, A., Klugewitz, K., Austrup, F., & Jablonski‐Westrich, D. (2000) · European Journal of Immunology · doi:10.1002/1521-4141(200011)30:11 · Cited by 111 · see citing works
Evolution of effectors and receptors of innate immunity
Magor, B. G., & Magor, K. E. (2001) · Developmental & Comparative Immunology · doi:10.1016/s0145-305x(01)00029-5 · Cited by 166 · see citing works
Inhibitory ITAMs as novel regulators of immunity
Blank, U., Launay, P., Benhamou, M., & Monteiro, R. C. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2009.00832.x · Cited by 168 · see citing works
“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…”
BackgroundInfluentialInflammatory 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 179 · see citing works
Ventilator-associated pneumonia: pathobiological heterogeneity and diagnostic challenges
Howroyd, F., Chacko, C. J., MacDuff, A., Gautam, N., Pouchet, B., Tunnicliffe, B., Weblin, J., Smith, F. G., Ahmed, Z., Duggal, N. A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50805-z · Cited by 182 · see citing works
KARAP/DAP12/TYROBP: three names and a multiplicity of biological functions
Tomasello, E., & Vivier, É. (2005) · European Journal of Immunology · doi:10.1002/eji.200425932 · Cited by 162 · see citing works
Genetics ignite focus on microglial inflammation in Alzheimer’s disease
Malik, M., Parikh, I., Vasquez, J. B., Smith, C., Tai, L., Bu, G., LaDu, M. J., Fardo, D. W., Rebeck, G. W., & Estus, S. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0048-1 · Cited by 161 · see citing works
“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.”
InfluentialNovel 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 161 · see citing works
Peripheral TREM1 responses to brain and intestinal immunogens amplify stroke severity
Liu, Q., Johnson, E. M., Lam, R. K., Wang, Q., Ye, H. B., Wilson, E. N., Minhas, P. S., Liu, L., Swarovski, M. S., Tran, S., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0421-2 · Cited by 159 · see citing works
Tomasello, E., Desmoulins, P.-O., Chemin, K., Guia, S., Cremer, H., Ortaldo, J. R., Love, P. E., Kaiserlian, D., & Vivier, É. (2000) · Immunity · doi:10.1016/s1074-7613(00)00035-2 · Cited by 159 · see citing works
Haure-Mirande, J.-V., Audrain, M., Ehrlich, M. E., & Gandy, S. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00552-w · Cited by 159 · see citing works
“Of note, while a low level of TREM3 is detected in mouse microglia, TREM3 in humans is present as a pseudogene [56, 70, 106].”
BackgroundGuruswamy, R., & ElAli, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18030496 · Cited by 159 · see citing works
“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;…”
BackgroundInfluentialErdman, 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 158 · see citing works
“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 ,
- 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
- 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
- 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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