Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages
Macrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. However, the factors that control macrophage behaviour in a context dependent manner are not well understood. Lipopolysaccharide (LPS) and the extracellular matrix glycoprotein...
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| Format: | Article |
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American Association for the Advancement of Science
2016
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| Online Access: | https://eprints.nottingham.ac.uk/35964/ |
| _version_ | 1848795198789779456 |
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| author | Piccinini, Anna M. Zuliani-Alvarez, Lorena Lim, Jenny M.P. Midwood, Kim S. |
| author_facet | Piccinini, Anna M. Zuliani-Alvarez, Lorena Lim, Jenny M.P. Midwood, Kim S. |
| author_sort | Piccinini, Anna M. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Macrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. However, the factors that control macrophage behaviour in a context dependent manner are not well understood. Lipopolysaccharide (LPS) and the extracellular matrix glycoprotein tenascin-C both activate toll-like receptor 4 (TLR4), and are released during bacterial infection and tissue injury, respectively. Here we report that these two TLR4 ligands induce distinct macrophage signalling pathways and phenotypes. Macrophages activated by LPS or tenascin-C display some common features, including NF-kB and MAP kinase signalling, and cytokine synthesis. However, different subsets of cytokines, and different phosphoproteomic signatures, are produced by each stimulus. Moreover, tenascin-C promotes macrophages more inclined to matrix synthesis and phosphorylation, whilst LPS-activated macrophages exhibit an elevated capacity to degrade matrix. These data reveal how activation of one pattern recognition receptor by different microenvironmental cues, signalling pathogen invasion or tissue damage, can create unique macrophage phenotypes. |
| first_indexed | 2025-11-14T19:28:17Z |
| format | Article |
| id | nottingham-35964 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:28:17Z |
| publishDate | 2016 |
| publisher | American Association for the Advancement of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-359642020-05-04T18:05:24Z https://eprints.nottingham.ac.uk/35964/ Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages Piccinini, Anna M. Zuliani-Alvarez, Lorena Lim, Jenny M.P. Midwood, Kim S. Macrophages exhibit a phenotypic plasticity that enables them to orchestrate specific immune responses to distinct threats. However, the factors that control macrophage behaviour in a context dependent manner are not well understood. Lipopolysaccharide (LPS) and the extracellular matrix glycoprotein tenascin-C both activate toll-like receptor 4 (TLR4), and are released during bacterial infection and tissue injury, respectively. Here we report that these two TLR4 ligands induce distinct macrophage signalling pathways and phenotypes. Macrophages activated by LPS or tenascin-C display some common features, including NF-kB and MAP kinase signalling, and cytokine synthesis. However, different subsets of cytokines, and different phosphoproteomic signatures, are produced by each stimulus. Moreover, tenascin-C promotes macrophages more inclined to matrix synthesis and phosphorylation, whilst LPS-activated macrophages exhibit an elevated capacity to degrade matrix. These data reveal how activation of one pattern recognition receptor by different microenvironmental cues, signalling pathogen invasion or tissue damage, can create unique macrophage phenotypes. American Association for the Advancement of Science 2016-08-30 Article PeerReviewed Piccinini, Anna M., Zuliani-Alvarez, Lorena, Lim, Jenny M.P. and Midwood, Kim S. (2016) Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages. Science Signaling, 9 (442). ISSN 1937-9145 http://stke.sciencemag.org/content/9/443/ra86 doi:10.1126/scisignal.aaf3596 doi:10.1126/scisignal.aaf3596 |
| spellingShingle | Piccinini, Anna M. Zuliani-Alvarez, Lorena Lim, Jenny M.P. Midwood, Kim S. Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages |
| title | Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages |
| title_full | Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages |
| title_fullStr | Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages |
| title_full_unstemmed | Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages |
| title_short | Distinct microenvironmental cues trigger divergent TLR4-mediated immune signalling in macrophages |
| title_sort | distinct microenvironmental cues trigger divergent tlr4-mediated immune signalling in macrophages |
| url | https://eprints.nottingham.ac.uk/35964/ https://eprints.nottingham.ac.uk/35964/ https://eprints.nottingham.ac.uk/35964/ |