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. 2009 Apr 16:4:12.
doi: 10.1186/1746-1596-4-12.

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

Bernhard Schaaf  1 , Karen Luitjens, Torsten Goldmann, Tobias van Bremen, Friedhelm Sayk, Christoph Dodt, Klaus Dalhoff, Daniel Droemann
Affiliations

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

Bernhard Schaaf et al. Diagn Pathol. .

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-alpha 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.

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Figures

Figure 1
Figure 1
A: Flow cytometry expression of TLR2, TLR4 and CD14 on monocytes. MFI ± SD is shown from healthy volunteers (H) and patients with sepsis (P). * = p < 0.01 vs. controls. MFI = mean fluorescence intensity. B: Correlation between TLR2 and TLR4 in patients with sepsis (r = 0.69, p < 0.001).
Figure 2
Figure 2
Flow cytometry expression of TLR2, TLR4 and CD14 on monocytes during course of sepsis. MFI ± SD is shown. * = p < 0.01 vs. t0. MFI = mean fluorescence intensity.
Figure 3
Figure 3
Correlation between TLR2 (A, r = 0.52; p = 0.02, figure 3a), CD14 (B, r = 0.49; p = 0.04, figure 3b) and IL-10 secretion of whole blood in response to LPS-stimulation at t2 in patients with sepsis.
See this image and copyright information in PMC

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