Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models.
The Gram-negative bacterium Burkholderia pseudomallei causes melioidosis and is a CDC category B bioterrorism agent. Toll-like receptor (TLR)-2 impairs host defense during pulmonary B.pseudomallei infection while TLR4 only has limited impact. We investigated the role of TLRs in B.pseudomallei-lipopo...
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0145397 |
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| author | Tassili A F Weehuizen Joann L Prior Thomas W van der Vaart Sarah A Ngugi Sergey A Nepogodiev Robert A Field Liesbeth M Kager Cornelis van 't Veer Alex F de Vos W Joost Wiersinga |
| author_facet | Tassili A F Weehuizen Joann L Prior Thomas W van der Vaart Sarah A Ngugi Sergey A Nepogodiev Robert A Field Liesbeth M Kager Cornelis van 't Veer Alex F de Vos W Joost Wiersinga |
| author_sort | Tassili A F Weehuizen |
| collection | DOAJ |
| description | The Gram-negative bacterium Burkholderia pseudomallei causes melioidosis and is a CDC category B bioterrorism agent. Toll-like receptor (TLR)-2 impairs host defense during pulmonary B.pseudomallei infection while TLR4 only has limited impact. We investigated the role of TLRs in B.pseudomallei-lipopolysaccharide (LPS) induced inflammation. Purified B.pseudomallei-LPS activated only TLR2-transfected-HEK-cells during short stimulation but both HEK-TLR2 and HEK-TLR4-cells after 24 h. In human blood, an additive effect of TLR2 on TLR4-mediated signalling induced by B.pseudomallei-LPS was observed. In contrast, murine peritoneal macrophages recognized B.pseudomallei-LPS solely through TLR4. Intranasal inoculation of B.pseudomallei-LPS showed that both TLR4-knockout(-/-) and TLR2x4-/-, but not TLR2-/- mice, displayed diminished cytokine responses and neutrophil influx compared to wild-type controls. These data suggest that B.pseudomallei-LPS signalling occurs solely through murine TLR4, while in human models TLR2 plays an additional role, highlighting important differences between specificity of human and murine models that may have important consequences for B.pseudomallei-LPS sensing by TLRs and subsequent susceptibility to melioidosis. |
| format | Article |
| id | doaj-art-fd71441681d2486eaba25efa5b15a2d1 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-fd71441681d2486eaba25efa5b15a2d12025-08-20T03:46:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014539710.1371/journal.pone.0145397Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models.Tassili A F WeehuizenJoann L PriorThomas W van der VaartSarah A NgugiSergey A NepogodievRobert A FieldLiesbeth M KagerCornelis van 't VeerAlex F de VosW Joost WiersingaThe Gram-negative bacterium Burkholderia pseudomallei causes melioidosis and is a CDC category B bioterrorism agent. Toll-like receptor (TLR)-2 impairs host defense during pulmonary B.pseudomallei infection while TLR4 only has limited impact. We investigated the role of TLRs in B.pseudomallei-lipopolysaccharide (LPS) induced inflammation. Purified B.pseudomallei-LPS activated only TLR2-transfected-HEK-cells during short stimulation but both HEK-TLR2 and HEK-TLR4-cells after 24 h. In human blood, an additive effect of TLR2 on TLR4-mediated signalling induced by B.pseudomallei-LPS was observed. In contrast, murine peritoneal macrophages recognized B.pseudomallei-LPS solely through TLR4. Intranasal inoculation of B.pseudomallei-LPS showed that both TLR4-knockout(-/-) and TLR2x4-/-, but not TLR2-/- mice, displayed diminished cytokine responses and neutrophil influx compared to wild-type controls. These data suggest that B.pseudomallei-LPS signalling occurs solely through murine TLR4, while in human models TLR2 plays an additional role, highlighting important differences between specificity of human and murine models that may have important consequences for B.pseudomallei-LPS sensing by TLRs and subsequent susceptibility to melioidosis.https://doi.org/10.1371/journal.pone.0145397 |
| spellingShingle | Tassili A F Weehuizen Joann L Prior Thomas W van der Vaart Sarah A Ngugi Sergey A Nepogodiev Robert A Field Liesbeth M Kager Cornelis van 't Veer Alex F de Vos W Joost Wiersinga Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models. PLoS ONE |
| title | Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models. |
| title_full | Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models. |
| title_fullStr | Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models. |
| title_full_unstemmed | Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models. |
| title_short | Differential Toll-Like Receptor-Signalling of Burkholderia pseudomallei Lipopolysaccharide in Murine and Human Models. |
| title_sort | differential toll like receptor signalling of burkholderia pseudomallei lipopolysaccharide in murine and human models |
| url | https://doi.org/10.1371/journal.pone.0145397 |
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