Perils and Promises of Pathogenic Protozoan Extracellular Vesicles

Abstract

Extracellular vesicles (EVs) are membranous structures formed during biological processes in living organisms. For protozoan parasites, secretion of EVs can occur directly from the parasite organellar compartments and through parasite-infected or antigen-stimulated host cells in response to in vitro and in vivo physiological stressors. These secreted EVs characteristically reflect the biochemical features of their parasitic origin and activating stimuli. Here, we review the species-specific morphology and integrity of parasitic protozoan EVs in concurrence with the origin, functions, and internalization process by recipient cells. The activating stimuli for the secretion of EVs in pathogenic protozoa are discoursed alongside their biomolecules and specific immune cell responses to protozoan parasite-derived EVs. We also present some insights on the intricate functions of EVs in the context of protozoan parasitism.

Functional Intricacy and Symmetry of Long Non-Coding RNAs in Parasitic Infections

“…There has been demonstration of intercommunication between Plasmodium and host cell that was facilitated by ncRNAs (Leitão et al, 2020). It is expected that selected lncRNAs in extracellular vesicles (EV) or secretome (SE) are involved in host-parasite interactions (Olajide and Cai, 2020;Moreno et al, 2021) (Figure 3). However, there is yet to be an explicit definition and identification of parasite lncRNAs in parasite-derived EVs and their possible inter-reactions with those of host origin.…”

Leishmania 360°: Guidelines for Exosomal Research

“…In general, LEVs are exported by either classical or non-classical molecular mechanisms and are involved in the transfer of biologically active molecules, including proteins, lipids, metabolites, miRNAs, and nucleic acids [86,90,91]. Although their role in the infectivity and development of Leishmania is still poorly understood, there is irrefutable evidence that LEVs have important functions, which require further research to clarify aspects such as their molecular pathways and host cells interactions (Figure 5) [8,14,[92][93][94]. The extracellular vesicles effector cargo is known to be delivered into the host target cells, stimulating both pro-and anti-inflammatory immune responses [14,40,[95][96][97].…”

“…The immune response is a critical aspect of the infection process and the establishment of the disease through the development of protective immunity associated with the intracellular destruction of the amastigotes by the macrophages, which will depend, in turn, on the induction of an efficient cellular response through the production of cytokines such as IFNγ, interleukins (IL), and TNF-α [20]. In vitro studies have shown that the LEVs of L. (L.) infantum recruited more macrophages and dendritic cells than other extracellular products or the parasite, which reflects the functional response of basal MHC-ll and decreased CD40 and CD 86 [8]. Many recent studies have shown that the presence of LEVs released from L. (L.) donovani modify the IFNγ-induced production of pro-or anti-inflammatory cytokines by cultured human monocytes, favoring the Th1 immune response and the elimination of Leishmania, which leads to the control the infection [1,69,96,118].…”

“…These hemoflagellates have a high level of genetic variability in vivo and a propensity for rapid evolution in culture medium, which supports the broadspectrum modulation of host immunity through extracellular vesicular communication, and enables these organisms to parasitize an enormous diversity of hosts, as well as being transiently infectious in humans (Figure 1) [4][5][6][7]. This ability to infect multiple species has facilitated the spread of Leishmania worldwide, and despite the development of some veterinary vaccines, the lack of effective vaccines and drug treatments for humans has allowed the rate of infections to continue to increase [8][9][10][11]. Promising new technology, including nanotechnological approaches, have developed over the past few decades to improve the prevention of leishmaniasis, the detection of the parasite, and its treatment [8,[11][12][13].…”

“…This ability to infect multiple species has facilitated the spread of Leishmania worldwide, and despite the development of some veterinary vaccines, the lack of effective vaccines and drug treatments for humans has allowed the rate of infections to continue to increase [8][9][10][11]. Promising new technology, including nanotechnological approaches, have developed over the past few decades to improve the prevention of leishmaniasis, the detection of the parasite, and its treatment [8,[11][12][13]. The importance of the extracellular vesicles has stimulated considerable interest in the scientific community, given their apparent potential for the development of effective diagnostic and therapeutic approaches, including the prediction of the outcome of the interaction between cells [14][15][16][17].…”