Abstract

Leishmania parasites are a group of kinetoplastid pathogens that cause a variety of clinical disorders while maintaining cell communication by secreting extracellular vesicles. Emerging technologies have been adapted for the study of Leishmania-host cell interactions, to enable the broad-scale analysis of the extracellular vesicles of this parasite. Leishmania extracellular vesicles (LEVs) are spheroidal nanoparticles of polydispersed suspensions surrounded by a layer of lipid membrane. Although LEVs have attracted increasing attention from researchers, many aspects of their biology remain unclear, including their bioavailability and function in the complex molecular mechanisms of pathogenesis. Given the importance of LEVs in the parasite-host interaction, and in the parasite-parasite relationships that have emerged during the evolutionary history of these organisms, the present review provides an overview of the available data on Leishmania, and formulates guidelines for LEV research. We conclude by reporting direct methods for the isolation of specific LEVs from the culture supernatant of the promastigotes and amastigotes that are suitable for a range of different downstream applications, which increases the compatibility and reproducibility of the approach for the establishment of optimal and comparable isolation conditions and the complete characterization of the LEV, as well as the critical immunomodulatory events triggered by this important group of parasites.

Highlights

  • 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]

  • The in vitro development, optimization, and evaluation of the physical and chemical characteristics of nanostructured lipid carriers (NLCs) for the encapsulation of BPQ and the evaluation of its solubility compared the promastigotes of L. (L.) amazonensis, L. (L.) braziliensis, and L. (L.) infantum samples [69]. These findings provide a baseline for an ample field of research, in which future studies may approach all these different aspects of the clinical role of Leishmania Leishmania extracellular vesicles (LEVs), especially those of drug-resistant strains, and how they contribute to the survival of the parasite over the course of its life cycle, offering potential approaches for diagnosis, follow-up treatment, the monitoring disease progression, prognosis, and new vaccine targets [3]

  • High performance methods for the isolation of products have been applied to research on protozoan extracellular vesicles, no consensus has been reached on the ultrasensitive detection of the specific biomarkers of different extracellular vesicle subtypes, which may originate endosomes, exosomes, derivatives of the plasma membrane or ectosomes, failing to define their specific biogenesis pathways reliably [18,91]

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Summary

Introduction

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]. We present an overview of this broad approach, with emphasis on the extracellular activity of the parasites of the genus

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