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

Tobias Van Bremen,Torsten Goldmann,Karin Luitjens,Klaus Dalhoff,Daniel Drömann,Bernhard Schaaf,Christoph Dodt

doi:10.1186/1746-1596-8-24

Abstract

BackgroundBacterial 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.MethodsIn 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.ResultsWe 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).ConclusionsPatients 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 SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4441869398748313

Highlights

Bacterial sepsis induced immunsuppression via antigen hyporesponsibility increases the risk of nosokomial infections and mortality
TLR2, TLR4, CD14, HLA DR and Trem-1 cell expression of sepsis patients compared to healthy controls The monocytes expression of Trem-1 and TLR2 was significant higher compared to healthy volunteers (p < 0.05)
In sepsis patients Trem-1 expression on neutrophils was associated with the IL-10 (LPS: r = 0,61, p < 0.02) and tumor necrosis factor (TNF)-α inducibility (LPS: r = 0,78, p < 0,002) (Figure 2)

Summary

Introduction

Bacterial sepsis induced immunsuppression via antigen hyporesponsibility increases the risk of nosokomial infections and mortality. Mortality in severe sepsis is dichotomic with mortality due to sequela of septic shock and multiorgan failure in the first days and mortality due to secondary, nosocomial infections later in the course of the disease. An active response to bacterial antigens via activation of immune cells leading to a cytokine response is necessary for the clearance of invading pathogens, but an uncontrolled excessive production of pro-inflammatory cytokines during infection such as tumor necrosis factor (TNF)-α, seems to be responsible for the clinical manifestation of septic shock and the mortality in the first days [2,3]. Bacterial antigen activates the innate immune system via pattern recognition receptors (PRR’s) on leucocytes and epithelial cells. In addition to the innate immunity with cytokine hyporesponsiveness a decreased activity of the adaptive immunity with reduced HLA-DR expression and antigen presentation is seen in sepsis [12]

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