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

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 (TL...

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Autores principales: Schaaf, Bernhard, Luitjens, Karen, Goldmann, Torsten, van Bremen, Tobias, Sayk, Friedhelm, Dodt, Christoph, Dalhoff, Klaus, Droemann, Daniel
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672063/
https://www.ncbi.nlm.nih.gov/pubmed/19371402
http://dx.doi.org/10.1186/1746-1596-4-12
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author Schaaf, Bernhard
Luitjens, Karen
Goldmann, Torsten
van Bremen, Tobias
Sayk, Friedhelm
Dodt, Christoph
Dalhoff, Klaus
Droemann, Daniel
author_facet Schaaf, Bernhard
Luitjens, Karen
Goldmann, Torsten
van Bremen, Tobias
Sayk, Friedhelm
Dodt, Christoph
Dalhoff, Klaus
Droemann, Daniel
author_sort Schaaf, Bernhard
collection PubMed
description 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.
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spelling pubmed-26720632009-04-23 Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes Schaaf, Bernhard Luitjens, Karen Goldmann, Torsten van Bremen, Tobias Sayk, Friedhelm Dodt, Christoph Dalhoff, Klaus Droemann, Daniel Diagn Pathol Research 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. BioMed Central 2009-04-16 /pmc/articles/PMC2672063/ /pubmed/19371402 http://dx.doi.org/10.1186/1746-1596-4-12 Text en Copyright © 2009 Schaaf et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Schaaf, Bernhard
Luitjens, Karen
Goldmann, Torsten
van Bremen, Tobias
Sayk, Friedhelm
Dodt, Christoph
Dalhoff, Klaus
Droemann, Daniel
Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes
title Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes
title_full Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes
title_fullStr Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes
title_full_unstemmed Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes
title_short Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes
title_sort mortality in human sepsis is associated with downregulation of toll-like receptor 2 and cd14 expression on blood monocytes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672063/
https://www.ncbi.nlm.nih.gov/pubmed/19371402
http://dx.doi.org/10.1186/1746-1596-4-12
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