title: Triggering receptor expressed on myeloid cells-2 protects against polymicrobial sepsis by enhancing bacterial clearance.
abstract: BACKGROUND
  Triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor primarily expressed on macrophages and monocyte-derived cells. TREM-2 not only functions as a regulator of inflammatory response, but also serves as a phagocytic receptor for bacteria. However, the role of TREM-2 in sepsis remains unknown.
  
  
  OBJECTIVE
  To investigate whether TREM-2 plays a role in sepsis.
  
  
  METHODS
  The manner of expression of TREM-2 was evaluated in patients with sepsis and in polymicrobial septic mouse model induced by the cecum ligation and puncture approach. Recombinant mouse TREM-2 was used to block the effect of TREM-2. Bone marrow-derived myeloid cells (BMMCs) that overexpress TREM-2 were administrated into septic mice at various times after cecum ligation and puncture.
  
  
  RESULTS
  The expression levels of TREM-2 were up-regulated in patients with sepsis and septic mice. The kinetics of TREM-2 expression in polymicrobial sepsis was comparable with that of bacteria burden in peritoneal lavage fluid. Blocking the effect of TREM-2 resulted in markedly increased mortality and bacterial burden in polymicrobial sepsis. Administration of TREM-2-overexpressing BMMCs significantly reduced the mortality, even when it was administered 4 hours after the initiation of sepsis. However, injection of TREM-2-overexpressing BMMCs into LPS-challenged endotoxemia mice did not improve the survival rate. The protective effect of TREM-2 in polymicrobial sepsis was not associated with its antiinflammatory properties, but it enhanced bacterial clearance in vivo. Furthermore, administration of TREM-2-overexpressing BMMCs improved the organ injury.
  
  
  CONCLUSIONS
  TREM-2 plays an important role in the host defense response to sepsis by enhancing bacterial clearance.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: QiXing
authors.initials: Q
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Jin
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.forename: Baoli
authors.initials: B
authors.lastname: Cheng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Shu
authors.forename: XiangMing
authors.initials: X
authors.lastname: Fang
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001201:Ascites / Q000378:metabolism; D058491:Bacterial Load / Q000276:immunology*; D060085:Coinfection / Q000276:immunology; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D011994:Recombinant Proteins; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology; D015854:Up-Regulation
chemical_list: D018793:Interleukin-13; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C498715:TREM2 protein, human; C498716:Trem2 protein, mouse; D015847:Interleukin-4