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Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages

Piccinini, Anna M.; Zuliani-Alvarez, Lorena; Lim, Jenny M.P.; Midwood, Kim S.

Authors

Anna M. Piccinini

Lorena Zuliani-Alvarez

Jenny M.P. Lim

Kim S. Midwood



Abstract

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.

Journal Article Type Article
Publication Date Aug 30, 2016
Journal Science Signaling
Print ISSN 1945-0877
Electronic ISSN 1937-9145
Publisher American Association for the Advancement of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 443
Article Number ra86
Pages ra86-ra86
APA6 Citation Piccinini, A. M., Zuliani-Alvarez, L., Lim, J. M., & Midwood, K. S. (2016). Distinct microenvironmental cues stimulate divergent TLR4-mediated signaling pathways in macrophages. Science Signaling, 9(443), ra86-ra86. https://doi.org/10.1126/scisignal.aaf3596
DOI https://doi.org/10.1126/scisignal.aaf3596
Publisher URL http://stke.sciencemag.org/content/9/443/ra86
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science signaling on 30 August 2016, Vol. 9, issue 443 DOI: 10.1126/scisignal.aaf3596

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Piccinini et al_Revised Manuscript file.pdf (638 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf


Piccinini et al_Revised Supplementary Materials.pdf (1.6 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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