Research ArticleImmunology

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

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Science Signaling  30 Aug 2016:
Vol. 9, Issue 443, pp. ra86
DOI: 10.1126/scisignal.aaf3596

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Macrophage plasticity

Macrophages have pattern recognition receptors, such as Toll-like receptors (TLRs), through which they detect infection or tissue injury and respond by promoting inflammation or inducing wound repair. Piccinini et al. investigated how macrophages interpret the bacterial product lipopolysaccharide (LPS) and the extracellular matrix component tenascin-C, both of which stimulate TLR4. Phosphoproteomic and gene expression analyses revealed that, although both stimuli activated some common signaling pathways, LPS-stimulated macrophages were biased toward matrix destruction, whereas tenascin-C–stimulated macrophages synthesized matrix components. Together, these data reveal how activation of a single receptor by diverse stimuli generates macrophages with distinct phenotypes so that these cells can either promote inflammation or induce tissue repair.

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