Innate Immune Recognition of Helminths: TLRs and Beyond

Helminth parasites are complex metazoans belonging to diverse taxonomic families, each exhibiting distinct host tissue tropisms as their larval stages migrate through various tissues to complete their life cycles. Migrating larvae through the host trigger tissue disruption/damage, leading to the release of damage-associated molecular patterns (DAMPs). In addition, helminth larvae and adults release excretory/secretory factors, including proteins, lipids, nucleic acids or carry bacterial symbionts, that act as pathogen-associated molecular patterns (PAMPs), which similar to DAMPs, are sensed by innate receptors [pattern recognition receptors (PRRs), and G protein-coupled receptors (GPCRs) and others] in the skin, liver, lungs, intestines, brain, or smooth muscles, triggering localised innate inflammatory responses. The host's innate immunity plays a central role in controlling the infection and/or inducing pathogenesis. This review provides a comprehensive examination of how innate immune receptors and their host- or helminth-derived ligands regulate the control and immunopathogenesis of helminth infections, thereby advancing our understanding of the early host signalling pathways and parasite-derived factors that initiate innate immune responses.