Membrane-bound extracellular vesicles secreted by parasitic protozoa: cellular structures involved in the communication between cells.

The focus of this review is a group of structures/organelles collectively known as extracellular vesicles (EVs) that are secreted by most, if not all, cells, varying from mammalian cells to protozoa and even bacteria. They vary in size: some are small (100-200 nm) and others are larger (> 200 nm). In protozoa, however, most of them are small or medium in size (200-400 nm). These include vesicles from different origins. We briefly review the biogenesis of this distinct group that includes (a) exosome, which originates from the multivesicular bodies, an important component of the endocytic pathway; (b) ectosome, formed from a budding process that takes place in the plasma membrane of the cells; (c) vesicles released from the cell surface following a process of patching and capping of ligand/receptor complexes; (d) other processes where tubules secreted by the parasite subsequently originate exosome-like structures. Here, special emphasis is given to EVs secreted by parasitic protozoa such as Leishmania, Trypanosoma, Plasmodium, Toxoplasma, Cryptosporidium, Trichomonas, and Giardia. Most of them have been characterized as exosomes that were isolated using several approaches and characterized by electron microscopy, proteomic analysis, and RNA sequencing. The results obtained show clearly that they present several proteins and different types of RNAs. From the functional point of view, it is now clear that the secreted exosomes can be incorporated by the parasite itself as well as by mammalian cells with which they interact. As a consequence, there is interference both with the parasite (induction of differentiation, changes in infectivity, etc.) and with the host cell. Therefore, the EVs constitute a new system of transference of signals among cells. On the other hand, there are suggestions that exosomes may constitute potential biotechnology tools and are important players of what has been designated as nanobiotechnology. They may constitute an important delivery system for gene therapy and molecular-displaying cell regulation capabilities when incorporated into other cells and even by interfering with the exosomal membrane during its biogenesis, targeting the vesicles via specific ligands to different cell types. These vesicles may reach the bloodstream, overflow through intercellular junctions, and even pass through the central nervous system blood barrier. There is evidence that it is possible to interfere with the composition of the exosomes by interfering with multivesicular body biogenesis.