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
<p>Abstract</p> <p>Background</p> <p>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,...
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-02-01
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| Series: | BMC Immunology |
| Online Access: | http://www.biomedcentral.com/1471-2172/10/9 |
| _version_ | 1818360781328089088 |
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| author | van Hellemond Jaap J Phylipsen Marion Retra Kim Everts Bart van Riet Elly Tielens Aloysius GM van der Kleij Desiree Hartgers Franca C Yazdanbakhsh Maria |
| author_facet | van Hellemond Jaap J Phylipsen Marion Retra Kim Everts Bart van Riet Elly Tielens Aloysius GM van der Kleij Desiree Hartgers Franca C Yazdanbakhsh Maria |
| author_sort | van Hellemond Jaap J |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 <it>Listeria monocytogenes </it>and <it>Escherichia coli </it>or the Th2 promoting helminth derived phospholipids from <it>Schistosoma mansoni </it>and <it>Ascaris lumbricoides</it>, all with TLR2 activating capacity.</p> <p>Results</p> <p>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) <it>p</it>-ERK/<it>p</it>-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.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-13T21:06:15Z |
| format | Article |
| id | doaj.art-d1bf01df4c684a5c9b862a60818664b6 |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-13T21:06:15Z |
| publishDate | 2009-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-d1bf01df4c684a5c9b862a60818664b62022-12-21T23:31:29ZengBMCBMC Immunology1471-21722009-02-01101910.1186/1471-2172-10-9Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: molecular correlates for Th1/Th2 polarizationvan Hellemond Jaap JPhylipsen MarionRetra KimEverts Bartvan Riet EllyTielens Aloysius GMvan der Kleij DesireeHartgers Franca CYazdanbakhsh Maria<p>Abstract</p> <p>Background</p> <p>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 <it>Listeria monocytogenes </it>and <it>Escherichia coli </it>or the Th2 promoting helminth derived phospholipids from <it>Schistosoma mansoni </it>and <it>Ascaris lumbricoides</it>, all with TLR2 activating capacity.</p> <p>Results</p> <p>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) <it>p</it>-ERK/<it>p</it>-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.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2172/10/9 |
| spellingShingle | van Hellemond Jaap J Phylipsen Marion Retra Kim Everts Bart van Riet Elly Tielens Aloysius GM van der Kleij Desiree Hartgers Franca C Yazdanbakhsh Maria 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 BMC Immunology |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://www.biomedcentral.com/1471-2172/10/9 |
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