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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 | Regulation of in- flammation by short chain fatty acids显示文摘 | Vinolo MA Rodrigues HG Nachbar RT | 2011 | Nutrients2011，3，10： | 1 |
| 3 | G-protein-coupled receptors as fat sensors显示文摘 | Marco A.R. Vinolo Sandro M. Hirabara Rui Curi | 2012 | Current Opinion in Clinical Nutrition and Metabolic Care2012，，2： | 1 |
| 4 | Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils显示文摘 | Marco A.R. Vinolo Hosana G. Rodrigues Elaine Hatanaka Fábio T. Sato Sandra C. Sampaio Rui Curi | 2011 | The Journal of Nutritional Biochemistry2011，，9： | 1 |
| 5 | Molecular targets related to inflammation and insulin resistance and potential in- terventions显示文摘 | Hirabara S M Gorjo R Vinolo M A | 2012 | J Biomed Biotechnol2012，，37： | 1 |
| 6 | Regulation of inflammation by short chain fatty acids显示文摘 | Vinolo MA Rodrigues HG Nachbar RT | 2011 | Nutrients2011，3，10： | 1 |
| 7 | Protein malnutrition induces bone marrow messenchymal stem cells commitment to adipogenicdifferentiation leading to hematopoietic failure显示文摘 | Cunha M C Lima Fda S Vinolo M A | | 0，，3： | 1 |
| 8 | Regulation of inflammation by short chain fat- ty acids 显示文摘 | VINOLO M A R RODRIGUES H G NACHBAR R T | 2011 | Nutrients2011，3，10： | 1 |
| 9 | Molecular Targets Related to Inflammation and Insulin Resistance and Potential Interventions显示文摘 | Sandro M. Hirabara Renata Gorj?o Marco A. Vinolo Alice C. Rodrigues Renato T. Nachbar Rui Curi Hartmut Jaeschke | 2012 | <journal-title>Journal of Biomedicine and Biotechnology2012，，： | 1 |
| 10 | Regulation of inflammation by short chain fatty acids显示文摘 | VINOLO M A RODRIGUES H G NACHBAR R T | 2011 | Nutrients2011，3，10： | 1 |
| 11 | The trimerization domain of NEMO is composed of the interacting C-terminal CC2 and LZ coiled-coil suhdomains 显示文摘 | Agou F Traincard F Vinolo E | 2004 | Biol Chem2004，279，27： | 1 |
| 12 | SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor显示文摘 | VINOLO M A FERGUSON G J KULKARNI S | 2011 | PLo S One2011，6，21： | 1 |
| 13 | Molecular targets related to inflammation and insulin resistance and potential interventions显示文摘 | Hirabara SM Gorjao R Vinolo MA | 2012 | J Biomed Biotechnol2012，13，： | 1 |
| 14 | Impairment of the hematological response and interleukin-1αproduction in protein-energy malnourished mice after endotoxemia with lipopolysaccharide显示文摘 | Fock RA Vinolo MA Blatt SL | 2012 | Braz J Med Biol Res2012，45，12： | 1 |
| 15 | Molecular targets related to inflammation and insulin resistance and potential interventions显示文摘 | Hirabara S M Gorjao R Vinolo M A | 2012 | J Biomed Biotechnol2012，2012，37： | 1 |
| 16 | G-Protein-coupled receptors as fat sensors 显示文摘 | Vinolo MA Hirabara SM Curl R | 2012 | Curr Opin Clin Nutr Metab Care2012，15，2： | 1 |
| 17 | Oral administration of oleic or linoleic acid accelerates the inflammatory phase of wound healing显示文摘 | Rodrigues HG Vinolo MA Magdalon J | 2012 | J Invest Dermatol2012，132，1： | 1 |
| 18 | Dietary glutamine sup- plementation increases the activity of peritoneal macrophages and hemopoiesis in earlyweaned mice inoculated with Mycobacterium bo- vis bacillus Calmette - Guerin 显示文摘 | Rogero M M Tirapegui J Vinolo M A | 2008 | J Nutr2008，138，7： | 1 |
| 19 | Effects of short chain fatty acids on effector mechanisms of neutrophils 显示文摘 | Vinolo M Hatganaka E Lambertucci R | 2009 | Cell Biochem Funct2009，27，1： | 1 |
| 20 | SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor 显示文摘 | Vinolo MA Ferguson GJ Kulkarni S | 2011 | PLoS One2011，6，21： | 1 |
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