Extracellular vesicles and leishmaniasis: Current knowledge and promising avenues for future development

Leishmania 360°: Guidelines for Exosomal Research

“…In this case, the proteinases of both the host (matrix metalloproteinases) and parasite (cysteine proteinases, metalloproteinases, and serine proteinases) affect the dynamics of the Leishmania infection [66,67]. These in vitro advances hint at a potential, previously unrecognized mechanism of Leishmania pathogenesis mediated by the Leishmania extracellular vesicles (LEVs) in the complex analysis of the dynamic molecular mechanisms of the Leishmania life cycle [5,68,69]. This indicates that the LEVs may play a significant role in the pathogenesis of a number of different parasite species, which hints at the potential therapeutic use of these substances in some cases [5,68,69].…”

“…These in vitro advances hint at a potential, previously unrecognized mechanism of Leishmania pathogenesis mediated by the Leishmania extracellular vesicles (LEVs) in the complex analysis of the dynamic molecular mechanisms of the Leishmania life cycle [5,68,69]. This indicates that the LEVs may play a significant role in the pathogenesis of a number of different parasite species, which hints at the potential therapeutic use of these substances in some cases [5,68,69]. The integrated understanding of these parasites (in the different clinical forms of leishmaniasis) and their activity patterns in their different forms of development and hosts is an ample field of research that reinforces the need to study the different species and the specific LEV pathways of their extracellular production in more detail.…”

“…In particular, GP63 is known to be significantly down-regulated and to shift its location in the parasite as promastigotes are transformed into amastigotes in the infected macrophages [34]. Given this shift in the location of the GP63 within the parasite, it is unclear whether the later stage macrophage infections, which harbor the amastigotes, continue to release GP63 into the exosomes [4,5,34,40,81], and it is not known whether the parasite molecules synthesized in the amastigotes found in the macrophages in long-term infections are released into the exosomes [35,40,54,68].…”

“…Parasites from the subfamily Leishmaniinae of medical and veterinary importance establish infection by releasing heterogeneous extracellular vesicles that carry large amounts of molecules (Figure 1) [1][2][3][4]. 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].…”

“…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]. Despite some advances, the mechanisms of the selective packaging of these extracellular vesicles are still poorly understood, and there is no consensus on the differential isolation and characterization of the extracellular vesicles or the ultrasensitive detection of specific extracellular vesicle subtypes, their specific biomarkers or their biogenesis (Figure 2) [5,[16][17][18][19]. Given these considerations, we present an overview of this broad approach, with emphasis on the extracellular activity of the parasites of the genus Leishmania.…”