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Open Access Research

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

Tobias van Bremen1, Daniel Drömann1, Karin Luitjens1, Christoph Dodt2, Klaus Dalhoff1, Torsten Goldmann3* and Bernhard Schaaf14

Author affiliations

1 Medical Clinic III, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, 23538, Germany

2 Präklinik, Medical Clinic München-Bogenhausen, München, 81925, Germany

3 Clinical and Experimental Pathology, Research Center Borstel, Airway Research Center North (ARCN), Member of the German Center for Lung Research, Borstel, 23845, Germany

4 Medical Clinic Nord, Clinic Dortmund, Dortmund, 44145, Germany

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Citation and License

Diagnostic Pathology 2013, 8:24  doi:10.1186/1746-1596-8-24

Published: 15 February 2013

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.

Virtual Slides

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

Keywords:
Triggering receptor expressed on myeloid cells − 1 (Trem-1); Sepsis; Hyporesponsiveness; Pattern recognition receptors (PRR); Neutrophils; Endotoxin tolerance