TREM-1 amplifies inflammation and is a crucial mediator of septic shock

Host innate responses to bacterial infections are primarily mediated by neu trophils and monocytes/macrophages(1,2). These cells express pattern recogn ition receptors (PRRs) that bind conserved molecular structures shared by g roups of microorganisms(3,4). Stimulation of PRR signalling pathways initia tes secretion of proinflammatory mediators(3,4), which promote the eliminat ion of infectious agents and the induction of tissue repair. Excessive infl ammation owing to bacterial infections can lead to tissue damage and septic shock(5-9). Here we show that inflammatory responses to microbial products are amplified by a pathway mediated by triggering receptor expressed on my eloid cells (TREM)-1. TREM-1 is an activating receptor expressed at high le vels on neutrophils and monocytes that infiltrate human tissues infected wi th bacteria. Furthermore, it is upregulated on peritoneal neutrophils of pa tients with microbial sepsis and mice with experimental lipopolysaccaride ( LPS)-induced shock. Notably, blockade of TREM-1 protects mice against LPS-i nduced shock, as well as microbial sepsis caused by live Escherichia coli o r caecal ligation and puncture. These results demonstrate a critical functi on of TREM-1 in acute inflammatory responses to bacteria and implicate TREM -1 as a potential therapeutic target for septic shock.