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| 1 | TREM-1 multimerization is essential for its activation on monocytes and neutrophils显示文摘The triggering receptor expressed on myeloid cells-1(TREM-1)is a receptor expressed on innate immune cells.By promoting the amplification of inflammatory signals that are initially triggered by Toll-like receptors(TLRs),TREM-1 has been characterized as a major player in the pathophysiology of acute and chronic inflammatory diseases,such as septic shock,myocardial infarction,atherosclerosis,and inflammatory bowel diseases.However,the molecular events leading to the activation of TREM-1 in innate immune cells remain unknown.Here,we show that TREM-1 is activated by multimerization and that the levels of intracellular Ca 2+release,reactive oxygen species,and cytokine production correlate with the degree of TREM-1 aggregation.TREM-1 activation on primary human monocytes by LPS required a two-step process consisting of upregulation followed by clustering of TREM-1 at the cell surface,in contrast to primary human neutrophils,where LPS induced a rapid cell membrane reorganization of TREM-1,which confirmed that TREM-1 is regulated differently in primary human neutrophils and monocytes.In addition,we show that the ectodomain of TREM-1 is able to homooligomerize in a concentration-dependent manner,which suggests that the clustering of TREM-1 on the membrane promotes its oligomerization.We further show that the adapter protein DAP12 stabilizes TREM-1 surface expression and multimerization.TREM-1 multimerization at the cell surface is also mediated by its endogenous ligand,a conclusion supported by the ability of the TREM-1 inhibitor LR12 to limit TREM-1 multimerization.These results provide evidence for ligand-induced,receptor-mediated dimerization of TREM-1.Collectively,our findings uncover the mechanisms necessary for TREM-1 activation in monocytes and neutrophils. | Kevin Carrasco Amir Boufenzer Lucie Jolly Helene Le Cordier Guanbo Wang Albert JR Heck Adelheid Cerwenka Emilie Vinolo Alexis Nazabal Alexandre Kriznik Pierre Launay Sebastien Gibot Marc Derive | 2019 | Cellular & Molecular Immunology2019，16，5： | 13 |
| 2 | Potentiation of NETs release is novel characteristic of TREM-1 activation and the pharmacological inhibition of TREM-1 could prevent from the deleterious consequences of NETs release in sepsis显示文摘During sepsis,neutrophil activation induces endothelial cell(EC)dysfunction partly through neutrophil extracellular trap(NET)release.The triggering receptor expressed on myeloid cell-1(TREM-1)is an orphan immune receptor that amplifies the inflammatory response mediated by Toll-like receptor-4(TLR4)engagement.Although the key role of TLR4 signaling in NETosis is known,the role of TREM-1 in this process has not yet been investigated.Here,we report that TREM-1 potentiates NET release by human and murine neutrophils and is a component of the NET structure.In contrast,pharmacologic inhibition or genetic ablation of TREM-1 decreased NETosis in vitro and during experimental septic shock in vivo.Moreover,isolated NETs were able to activate ECs and impair vascular reactivity,and these deleterious effects were dampened by TREM-1 inhibition.TREM-1 may,therefore,constitute a new therapeutic target to prevent NETosis and associated endothelial dysfunction. | Amir Boufenzer Kevin Carrasco Lucie Jolly Benjamin Brustolin Elisa Di-Pillo Marc Derive Sébastien Gibot | 2021 | Cellular & Molecular Immunology2021，18，2： | 9 |
| 3 | sTREM-1 is a specific biomarker of TREM-1 pathway activation显示文摘TREM-1(triggering receptor expressed on myeloid cells-1)is a transmembrane receptor expressed by innate immune cells,including endothelial cells and platelets.TREM-1 is a crucial mediator of septic shock that acts by synergizing with Toll-like receptors(TLRs)to amplify the inflammatory responses to pathogens,thus promoting sepsis-induced immune dysregulation and organ dysfunction[1,2,3]. | Lucie Jolly Kévin Carrasco Margarita Salcedo-Magguilli Jean-Jacques Garaud Simon Lambden Tom van der Poll Alexandre Mebazaa Pierre-François Laterre Sebastien Gibot Amir Boufenzer Marc Derive | 2021 | Cellular & Molecular Immunology2021，18，8： | 8 |
| 4 | High-mobility group box 1 protein plasma concentrations during septic shock显示文摘 | Sébastien Gibot Frédéric Massin Aurélie Cravoisy Damien Barraud Lionel Nace Brune Levy Pierre-Edouard Bollaert | 2007 | Intensive Care Medicine2007，，8： | 2 |
| 5 | Effects of the TREM-1 pathway modulation during mesenteric ischemia-reperfusion in rats显示文摘 | Gibot S Maasin F Alauzet C | 2008 | Crit Care Med2008，36，2： | 1 |
| 6 | Room-temperature single-phase Li insertion/extraction in nanoscale LiFePO4显示文摘 | GIBOT P MONTSE C C LAFFONT L | 2008 | Na- ture Materials2008，7，： | 1 |
| 7 | Time-course of sTREM(soluble triggering receptor expressed on myeloid cells)-1,procalcitonin,and C-reactive protein plasma concentrations during sepsis显示文摘 | Gibot S Cravoisy Akolopp-Sarda Béné MC Faure G | 2005 | Crit Care Med2005，33，4： | 1 |
| 8 | Relation between muscle Na + K + ATPase activity and raised lactate concentrations in septic shock: a prospective study显示文摘 | Levy B Gibot S Franck P | 2005 | Lancet2005，365，9462： | 1 |
| 9 | TREM-1 promotes survival during septic shock in mice 显示文摘 | Gibot S Massin F Marcou M | 2007 | Eur J Immunol2007，37，2： | 1 |
| 10 | Plasma level of a triggering receptor expressed on myeloid cells-1:its diagnostic accuracy in patients will suspected sepsis显示文摘 | Gibot S Kolopp-Sarda M-N | | 0，，01： | 1 |
| 11 | Soluble triggering receptor expressed on myeloid cells and diagnosis of pneumonia显示文摘 | Gibot S Craviosy A Levy B | 2004 | N Engl J Med2004，350，： | 1 |
| 12 | Plasma level of a triggering receptor expressed on myeloid cells 1 : its diagnostic accuracy in patients with suspected sepsis 显示文摘 | Gibot S Kolopp Sarda MN Be'ne' MC | 2004 | Ann Intern Med2004，141，1： | 1 |
| 13 | Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock:a prospective study显示文摘 | Levy B Gibot S Franek P | 2005 | Lancet2005，365，9462： | 1 |
| 14 | Plasma level of a triggering receptor expressed on myeloid cells-1:its diagnostic accuracy in patients with suspected sepsis显示文摘 | Gibot S Kolopp-Sarda MN Bene MC | 2004 | Ann Intern Med2004，141，1： | 1 |
| 15 | Plasma level of a triggering receptor expressed on myeloid cells: its diagnostic accuracy in patients with suspected sepsis显示文摘 | Gibot S Kolopp-Sarda MN Bene MC | 2004 | Ann Intern Med2004，141，1： | 1 |
| 16 | Soluble triggering receptor ex- pressed on myeloid cells and the diagnosis of pneumonia显示文摘 | Gibot S Cravoisy A Levy B | 2004 | N Engl J Med2004，350，5： | 1 |
| 17 | Urine sTREM-1 assessment in diagnosing sepsis and sepsis-related acute kidney injury显示文摘 | Derive M Gibot S | 2011 | Crit Care2011，15，6： | 1 |
| 18 | Study of the LiFePOdFePO4 two-phase system by high-resolution electron energy loss spectroscopy显示文摘 | Laffont L Delacourt C Gibot P | 2006 | Chemistry of Mate- dais2006，18，23： | 1 |
| 19 | Sueface triggering receptor expressed on myeloid cells I expression patterns in septic shock显示文摘 | Gibot S Renard PE Bollaert PE | 2005 | Intensive Care Med2005，31，4： | 1 |
| 20 | Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia显示文摘 | Gibot S Cravoisy A Levy B | 2004 | N Engl J Med2004，350，5： | 1 |
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