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John F. Foley

A tale of two signals

2 min read

In their Science Signaling paper, Kim Midwood and colleagues from the University of Oxford investigated how macrophages, among the earliest responding cells of the immune system, interpret two different signals through the same receptor. The first signal, lipopolysaccharide (LPS), is a microbial product that stimulates Toll-like receptor 4 (TLR4) to induce the production of inflammatory factors. The second, tenascin-C, is an extracellular matrix protein that also acts as a TLR4 agonist. Under normal conditions, tenascin-C is present in low amounts, but its abundance is increased in the context of tissue damage. The authors used proteomics and gene expression analysis to show that exposure of macrophages to LPS caused them to adopt an inflammatory phenotype and make factors that degrade the extracellular matrix. However, when exposed to tenascin-C, the macrophages were less inflammatory and instead produced factors that repair the matrix. Given that TLR4 drove both of these distinct responses, the next step is to figure out the different mechanisms involved. Together, these findings suggest that the behavior of macrophages can be tuned by a single receptor that interprets distinct signals present in the tissue microenvironment.

To see the abstract of this research article, go here:

For a nice write-up of the paper in The Scientist, follow this link: