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BMC Immunology
Published in: BMC Immunology 1/2009

Open Access 01-12-2009 | Research article

Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization

Authors: Elly van Riet, Bart Everts, Kim Retra, Marion Phylipsen, Jaap J van Hellemond, Aloysius GM Tielens, Desiree van der Kleij, Franca C Hartgers, Maria Yazdanbakhsh

Published in: BMC Immunology | Issue 1/2009

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Abstract

Background

Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing capacities are still poorly defined. To address this issue, the molecular profile of human monocyte derived DCs was characterized after exposure to TLR4 ligand LPS in combination with the Th1 promoting bacterial extracts from Listeria monocytogenes and Escherichia coli or the Th2 promoting helminth derived phospholipids from Schistosoma mansoni and Ascaris lumbricoides, all with TLR2 activating capacity.

Results

With regard to the signalling pathways activated upon exposure to LPS and the TLR2 activating compounds, we find that the ratio of activated Mitogen Activated Protein Kinases (MAPK) p-ERK/p-p38 is lower in DCs stimulated with the bacterial products compared to DCs stimulated with the helminth products, which correlates with the Th1 and Th2 polarizing capacity of these compounds. Furthermore, analysis of the mRNA expression levels of a set of 25 carefully selected genes potentially involved in modulation of T cell polarization revealed that the mRNA expression of notch ligand delta-4 and transcription factor c-fos are differentially regulated and show a strong correlation with Th1 and Th2 polarization, respectively.

Conclusion

This study shows that combined TLR2 and TLR4 activation in the context of different antigen sources can induce very distinct molecular profiles in DCs and suggests that the Th1/Th2 polarizing capacity of compounds can be predicted with the molecular signature they induce in DCs.
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Metadata
Title
Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarization
Authors
Elly van Riet
Bart Everts
Kim Retra
Marion Phylipsen
Jaap J van Hellemond
Aloysius GM Tielens
Desiree van der Kleij
Franca C Hartgers
Maria Yazdanbakhsh
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2009
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-10-9

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