Investigation of parasite-host interactions through the study of extracellular vesicles and in vitro models

Background: Helminths are able to install an immunoregulatory environment within their hosts, thus ensuring their survival, an adaption ascribed to long lasting coevolution processes. This modulation of the host’s defense system is achieved by several mechanisms such as the induction of apoptosis in immune cells, the manipulation of Pattern Recognition Receptors (PRRs) or the suppression of Th1/Th2 cells and cytokines. In recent years, Extracellular Vesicles (EVs), i.e. membrane-enclosed nanoparticles containing soluble proteins, carbohydrates, lipids and nucleic acids, have been described for playing a central role in parasite-host communication. Many parasite species have shown to be able to release Evs as a strategy to deliver immunomodulatory components involved in immune evasion and pathogenesis, being possibly involved in tumorigenesis. Objectives: We aim to investigate the cross-talk between a number of nematode species (Ascaris sp, Anisakis sp, Dirofilaria sp) and the human host through genomic, transcriptomic, and proteomic assays, examining, in detail, Evs features, and using in vitro cutting-edge models including 2D and 3D human organoids. Expected (or preliminary) results: Since the full pathogenic potential of parasitic helminths has not been entirely explored, basic knowledge from the characterization of Evs can be of pivotal importance for advancements within this field. Evs may contain bioactive compounds which possibly have a role in the modulation of the expression of host genes involved in immune response, inflammation and pathogenesis. Future perspectives: The increased understanding of interspecific crosstalk strategies can indeed open up new avenues for vaccine, diagnostic, and therapeutic development for a wide variety of diseases involved with parasite infection, such as cancers and immunological disorders. For instance, in the future, EVs may be explored as vaccine candidates with a potential regulatory effect on the onset and outcome of parasite infections.