Helminth extracellular vesicles: Roles in and beyond host-parasite communication

Parasitic worms (helminths) release extracellular vesicles (EVs) -membrane-surrounded, nanosized structures loaded with a repertoire of active biomolecules- as part of their excretory/secretory products. These particles play key roles in intercellular communication, not only within multicellular organisms but also between organisms that establish stable biological associations, as it occurs during parasitism. Since their "rediscovery" in 2012, the field of helminth EVs has expanded significantly, with a wealth of research conducted both in model organisms and parasites of human and veterinary importance. These investigations have revealed that helminth EVs play active roles in host-parasite interactions. In this article, we review milestone literature on helminth EVs and point out remaining knowledge gaps regarding several aspects of their biogenesis, composition, and interaction with the host. Furthermore, we outline current perspectives on the potential application of these bio-nanoparticles to the theragnostic of helminth infections, highlighting the main challenges hindering the translation of experimental evidence into actual EV-based tools for the control of human and livestock helminthiases.