Rethinking Toll-like receptor signalling

Since the discovery of Toll and Toll-like receptors (TLRs) in the 90s, an extensive body of research has been performed to determine how Pattern Recognition Receptors (PRRs) recognise 'ligands' and signal. The families of PRRs now include membrane and cytosolic proteins, which broadly signal by forming large protein platforms or supramolecular organising centres (SMOCs). The concept of SMOC-driven signalling has led to the development of a set of assumptions, particularly for TLRs, based on experimental data, to explain the physiological consequences of PRR activation. Recent research suggests that at least some of these assumptions should be reconsidered, especially as many of these receptors are important therapeutic targets for drug development, so understanding the mechanisms by which they signal is critical.