Extracellular vesicle-associated microRNA in human parasitic diseases

Parasitic infections are a global problem in the tropics, subtropics, and temperate climates. There are three main types of parasites that infect humans and cause disease: helminths, parasitic worms (e.g., Schistosomes, Wuchereria bancrofti, etc.), protozoan unicellular eukaryotic parasites (e.g., Plasmodium, Toxoplasma, Leishmania, and Trypanosoma), and ectoparasites, an organism that lives on the skin of their hosts, such as Sarcoptes scabiei. Nearly 1 billion people worldwide suffer from various parasitic diseases. Extracellular vesicles (EVs) are vesicles of endocytic origin secreted by all eukaryotic cells, which contain a variety of molecules, including lipids, proteins, and nucleic acids (RNAs), some of which have immunomodulatory properties. The EVs produced through the endocytic pathways are known as exosomes, whereas microvesicles are formed by the shedding of the plasma membrane. Exosomes usually range in size from 50 to 150 nm, have a distinctive cup-shaped morphology, and express markers related to their formation, which comprises the inward budding of multivesicular structures. However, extracellular fission and outward budding of the plasma membrane result in the formation of microvesicles, whereas apoptotic bodies occur when cells undergo apoptosis. These subtypes have a larger size range (50–2000 and 50–5000 nm) and lack the cup-shaped morphology unique to exosomes. Despite the above features, it is difficult to distinguish exosomes from other EVs, and there is no appropriate marker for their detection. Numerous studies have shown that the synthesis of EVs by parasites is an essential component of their life cycle and the progression of the infection; it follows that these are required for their survival. EVs offer a reliable delivery method to promote parasite development, the transmission of virulence factors, adhesion to host tissues, and the evasion of immune responses in host cells. They are successful in controlling the immune response of the host by triggering or suppressing the responses, as well as by having an impact on a variety of other (nonimmune) target cells. The parasite-infected host EVs make the naïve host cells more susceptible to diseases through intracellular communication. EVs produced by parasites act as a pathway for importing parasite payload into host cells. This parasite cargo could contain virulence components from a variety of protozoans, such as Trypanosoma cruzi, Trypanosoma brucei, Leishmania spp., Plasmodium falciparum, Toxoplasma gondii, and helminths.