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Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes

Bernhard Schaaf1, Karen Luitjens2, Torsten Goldmann3, Tobias van Bremen2, Friedhelm Sayk4, Christoph Dodt5, Klaus Dalhoff2 and Daniel Droemann2*

Author affiliations

1 Medical Clinic Nord, Clinic Dortmund, 44145 Dortmund, Germany

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

3 Clinical and Experimental Pathology, Research Center Borstel, 23845 Borstel, Germany

4 Medical Clinic I, University of Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany

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

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Citation and License

Diagnostic Pathology 2009, 4:12  doi:10.1186/1746-1596-4-12

Published: 16 April 2009

Abstract

Pattern recognition receptors are a key component of the first line host defense against infection, recognizing specific microbial products. We hypothesize that monocyte hyporesponsiveness in human sepsis is associated with a downregulation of the pattern recognition receptors Toll-like receptor (TLR)-2 and TLR4.

Protein expression of CD14, TLR2 and TLR4 on blood monocytes was examined using flow cytometry from 29 patients with sepsis and 14 healthy controls. In addition LPS stimulated TNF-α and IL-10 production was studied in a 24 hour whole blood assay.

We found an increased expression of CD14, TLR2 and TLR4 in patients with sepsis compared to controls (p < 0.01). In patients with sepsis, death was associated with significant lower CD14 and TLR2 expression at admission (CD14: 25.7 +- 19.1 vs 39.1 +- 17.3 mean fluorescence intensity [MFI], p = 0.02; TLR2: 21.8 +- 9.4 vs. 30.9 +- 9.6, p = 0.01). At 72 hours the TLR2 expression on monocytes was associated with the IL-10 inducibility after LPS stimulation (r = 0.52, p = 0.02) and the CD14 expression with the IL-6, IL-10 and TNF inducibility.

We conclude that septic patients are characterized by an increased expression of CD14, TLR2 and TLR4 on monocytes compared to controls. Death is associated with downregulation of TLR2 and CD14 expression on monocytes correlating with reduced cytokine inducibility. We suggest that CD14 and TLR2 are a key factor in monocyte hyporesponsibility during severe sepsis.