title: Blocking TREM-1 signaling prolongs survival of mice with Pseudomonas aeruginosa induced sepsis.
abstract: TREM-1 is a recently discovered receptor expressed on neutrophils and macrophages. Blocking of TREM-1 signaling improves the survival of mice with bacterial sepsis. However, the precise mechanism by which TREM-1 modulates the inflammatory responses is poorly defined. In this study, we investigated the role of TREM-1 in Pseudomonas aeruginosa-induced peritonitis. Our results showed that TREM-1 was not expressed on lymphocytes but emerged on the cell surface of neutrophils and peritoneal macrophages. Blockade of TREM-1 signaling significantly prolonged survival of mice with P. aeruginosa-induced peritonitis. However, blocking TREM-1 signaling had no effect on macrophage phagocytosis in vitro. Interestingly, the expression of the costimulatory molecules CD40 and CD86 on macrophages was significantly decreased after blocking TREM-1 signaling. Furthermore, interfering with TREM-1 engagement led to significant reduction of pro-inflammatory mediators such as IL-1, TNF-α, MCP-1 and IFN-γ. Therefore, our results showed that TREM-1 could be a potential therapeutic target for bacterial sepsis.
authors: Department of Clinical Laboratory, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Feng
authors: F
authors: Wang
authors: Shuanglin
authors: S
authors: Liu
authors: Shiji
authors: S
authors: Wu
authors: Qin
authors: Q
authors: Zhu
authors: Guoping
authors: G
authors: Ou
authors: Cailin
authors: C
authors: Liu
authors: Yue
authors: Y
authors: Wang
authors: Yalong
authors: Y
authors: Liao
authors: Ziyong
authors: Z
authors: Sun
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000235:genetics; D016470:Bacteremia / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D001792:Blood Platelets / Q000378:metabolism; D019013:CD40 Antigens / Q000235:genetics; D018932:Chemokine CCL2 / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000378:metabolism; D010538:Peritonitis / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis; D011552:Pseudomonas Infections / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma