Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function

Abstract TLR4 location, and bacterial species-derived lipopolysaccharides, play a significant role in the downstream activation of transcription factors, accessory molecules, and products. Here, this is demonstrated through the use of classically-activated and alternatively-activated macrophages. We...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Matthew Stephens, Shan Liao, Pierre-Yves von der Weid
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a047d45fcc244d60a2d23de69eade9cd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a047d45fcc244d60a2d23de69eade9cd
record_format	dspace
spelling	oai:doaj.org-article:a047d45fcc244d60a2d23de69eade9cd2021-12-02T14:12:08ZUltra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function10.1038/s41598-020-79145-w2045-2322https://doaj.org/article/a047d45fcc244d60a2d23de69eade9cd2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79145-whttps://doaj.org/toc/2045-2322Abstract TLR4 location, and bacterial species-derived lipopolysaccharides, play a significant role in the downstream activation of transcription factors, accessory molecules, and products. Here, this is demonstrated through the use of classically-activated and alternatively-activated macrophages. We show that, when polarized, human macrophages differentially express and localize TLR4, resulting in biased recognition and subsequent signalling of LPS derived from Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica. Analysis of activation demonstrated that in classically activated macrophages, P. aeruginosa signals from the plasma membrane via TLR4 to p65 dependent on TAK1 and TBK1 signalling. E. coli signals dependent or independent of the endosome, utilizing both TAK1- and TBK1-signalling to induce P65 and IRF3 inducible genes and cytokines. S. enterica however, only induces P65 and IRF3 phosphorylation through signalling via the endosome. This finding outlines clear signalling mechanisms by which innate immune cells, such as macrophages, can distinguish between bacterial species and initiate specialized responses through TLR4.Matthew StephensShan LiaoPierre-Yves von der WeidNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew Stephens Shan Liao Pierre-Yves von der Weid Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function
description	Abstract TLR4 location, and bacterial species-derived lipopolysaccharides, play a significant role in the downstream activation of transcription factors, accessory molecules, and products. Here, this is demonstrated through the use of classically-activated and alternatively-activated macrophages. We show that, when polarized, human macrophages differentially express and localize TLR4, resulting in biased recognition and subsequent signalling of LPS derived from Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica. Analysis of activation demonstrated that in classically activated macrophages, P. aeruginosa signals from the plasma membrane via TLR4 to p65 dependent on TAK1 and TBK1 signalling. E. coli signals dependent or independent of the endosome, utilizing both TAK1- and TBK1-signalling to induce P65 and IRF3 inducible genes and cytokines. S. enterica however, only induces P65 and IRF3 phosphorylation through signalling via the endosome. This finding outlines clear signalling mechanisms by which innate immune cells, such as macrophages, can distinguish between bacterial species and initiate specialized responses through TLR4.
format	article
author	Matthew Stephens Shan Liao Pierre-Yves von der Weid
author_facet	Matthew Stephens Shan Liao Pierre-Yves von der Weid
author_sort	Matthew Stephens
title	Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function
title_short	Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function
title_full	Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function
title_fullStr	Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function
title_full_unstemmed	Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function
title_sort	ultra-purification of lipopolysaccharides reveals species-specific signalling bias of tlr4: importance in macrophage function
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a047d45fcc244d60a2d23de69eade9cd
work_keys_str_mv	AT matthewstephens ultrapurificationoflipopolysaccharidesrevealsspeciesspecificsignallingbiasoftlr4importanceinmacrophagefunction AT shanliao ultrapurificationoflipopolysaccharidesrevealsspeciesspecificsignallingbiasoftlr4importanceinmacrophagefunction AT pierreyvesvonderweid ultrapurificationoflipopolysaccharidesrevealsspeciesspecificsignallingbiasoftlr4importanceinmacrophagefunction
_version_	1718391801252937728

Ultra-purification of Lipopolysaccharides reveals species-specific signalling bias of TLR4: importance in macrophage function

Ejemplares similares