• QiXing Chen, Kai Zhang, Yue Jin, Tao Zhu, Baoli Cheng, Qiang Shu, and XiangMing Fang.
• Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
• Am. J. Respir. Crit. Care Med.. 2013 Jul 15;188(2):201-12.

RationaleTriggering 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.ObjectivesTo investigate whether TREM-2 plays a role in sepsis.MethodsThe 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.Measurements And Main ResultsThe 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.ConclusionsTREM-2 plays an important role in the host defense response to sepsis by enhancing bacterial clearance.

36 keywords...

hide…