Differential toll-like receptor-signalling of Burkholderia pseudomallei lipopolysaccharide in murine and human models

Weehuizen, Tassili A. F., Prior, Joann L., van der Vaart, Thomas W., Ngugi, Sarah A., Nepogodiev, Sergey A., Field, Robert A. ORCID: https://orcid.org/0000-0001-8574-0275, Kager, Liesbeth M., van 't Veer, Cornelis, de Vos, Alex F. and Wiersinga, W. Joost (2015) Differential toll-like receptor-signalling of Burkholderia pseudomallei lipopolysaccharide in murine and human models. PLoS One, 10 (12). ISSN 1932-6203

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Abstract

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.

Item Type:	Article
Additional Information:	Publisher Copyright: © 2015 Weehuizen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords:	general ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	04 Sep 2024 13:35
Last Modified:	25 Sep 2024 18:06
URI:	https://ueaeprints.uea.ac.uk/id/eprint/96534
DOI:	10.1371/journal.pone.0145397

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