Toll-Like Receptors in Innate Immunity: Signalling Pathways and Therapeutic Targets

Abstract

Toll-like receptors (TLRs) are among the best-characterised sensors of the innate immune system, and the signalling pathways downstream of them have been mapped in considerable detail over roughly two decades. This narrative review summarises what the published literature says about how TLRs recognise microbial and host-derived molecules, how the adaptor proteins MyD88 and TRIF route the signal to inflammatory and interferon responses, and what has happened when those pathways have been used as therapeutic targets. It reports no new data and rests on a non-systematic reading of the literature up to 2020. The pathway map is clearer than the clinical picture: agonists have found a place as vaccine adjuvants and topical immune modifiers, whereas antagonists tested in sepsis did not deliver the benefit that the biology had suggested. Redundancy among receptors, differences between species, context-dependent roles for the same receptor in defence and in tissue injury, and uncertainty about endogenous ligands help to explain that gap. The review closes with the questions that future work needs to address before receptor-level intervention can be expected to perform reliably in patients.