title: Triggering receptor expressed on myeloid cells-1 (Trem-1) on blood neutrophils is associated with cytokine inducibility in human E. coli sepsis.
abstract: BACKGROUND
  Bacterial sepsis induced immunsuppression via antigen hyporesponsibility increases the risk of nosokomial infections and mortality. Pattern recognition receptors (PRR) might have a central role in the pathophysiology of hyporesponsibility.
  
  
  METHODS
  In this study we evaluated in a human E. coli sepsis cohort, the role of PRR including TLR's and Trem-1. Expression of Trem-1, TLR2, TLR4, CD14 and HLA-DR on blood monozytes and neutrophils were examined using flow cytometry from 22 patients with E. coli sepsis and 6 healthy controls. LPS and LTA stimulated TNF alpha, IL-10, IL-8 and IL-6 production was studied in a 24 h whole blood assay. Free cytokine serum concentration of TNF alpha, PCT and IP-10 were evaluated.
  
  
  RESULTS
  We found a significant higher expression of Trem-1 and TLR-2 on monocytes and neutrophils in patients compared to healthy volunteers. TLR2 expression (p < 0.05) was higher and HLA-DR lower (p < 0.05) on monocytes of patients with severe sepsis compared to patients with simple sepsis. Trem-1 expression was tendentially higher (p = 0,07) on monocytes and lower on neutrophils of patients with severe sepsis. Trem-1 expression on neutrophils was associated with the IL-10 (LPS: r = 0,61, p < 0.02) and TNF-α inducibility (LPS: r = 0,78, p < 0,002). In addition Trem-1 expression on neutrophils shows a negative correlation to the serum levels of TNF alpha (r = -0,63; p < 0,005), IP-10 (r = -0,5; p < 0,035) and procalcitonin (r = -0,59; p < 0,007).
  
  
  CONCLUSIONS
  Patients with E. coli sepsis are characterized by an association of Trem-1 expression on blood neutrophils with cytokine inducibility. The TREM-1 pathway on neutrophils might play a role in producing an adequate inflammatory and bactericidal response in bacterial sepsis.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4441869398748313.
authors: Medical Clinic III, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck 23538, Germany.
authors: Tobias
authors: T
authors: van Bremen
authors: Daniel
authors: D
authors: Drömann
authors: Karin
authors: K
authors: Luitjens
authors: Christoph
authors: C
authors: Dodt
authors: Klaus
authors: K
authors: Dalhoff
authors: Torsten
authors: T
authors: Goldmann
authors: Bernhard
authors: B
authors: Schaaf
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D004927:Escherichia coli Infections / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D011446:Prospective Studies; D011971:Receptors, Immunologic / Q000097:blood*; D018805:Sepsis / Q000097:blood / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000097:blood; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; D006684:HLA-DR Antigens; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; C408842:TREM1 protein, human; D051195:Toll-Like Receptor 2; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10