Triggering receptor expressed on myeloid cells-1 (Trem-1) on blood neutrophils is associated with cytokine inducibility in human E. coli sepsis

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-alpha 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. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4441869398748313