Unveiling the role of EVs in anaerobic parasitic protozoa

Sabatke, Bruna; Gavinho, Bruno; Cóceres, Verónica M.; Miguel, Natalia de; Ramirez, Marcel I.

doi:10.1016/j.molimm.2021.02.007

Cited by 15 publications

(14 citation statements)

References 97 publications

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“…For instance, EVs released by malignant brain cells have been shown to promote the progression of brain metastases ( Sirkisoon et al., 2022 ). Likewise, the parasitic cells use EVs to transfer cargoes in modulating the host immune system ( Sabatke et al., 2021 ). It has been reported that giardial multicellular vesicles (MVs) are absorbed by dendritic cells, resulting in increased allostimulation ( Evans-Osses et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Giardial lipid rafts share virulence factors with secreted vesicles and participate in parasitic infection in mice

Grajeda

Chatterjee

Villalobos

et al. 2022

Front. Cell. Infect. Microbiol.

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Giardia lamblia, a protozoan parasite, is a major cause of waterborne infection, worldwide. While the trophozoite form of this parasite induces pathological symptoms in the gut, the cyst form transmits the infection. Since Giardia is a noninvasive parasite, the actual mechanism by which it causes disease remains elusive. We have previously reported that Giardia assembles cholesterol and GM1 glycosphingolipid-enriched lipid rafts (LRs) that participate in encystation and cyst production. To further delineate the role of LRs in pathogenesis, we isolated LRs from Giardia and subjected them to proteomic analysis. Various cellular proteins including potential virulence factors—e.g., giardins, variant surface proteins, arginine deaminases, elongation factors, ornithine carbomyltransferases, and high cysteine-rich membrane proteins—were found to be present in LRs. Since Giardia secretes virulence factors encapsulated in extracellular vesicles (EVs) that induce proinflammatory responses in hosts, EVs released by the parasite were isolated and subjected to nanoparticle tracking and proteomic analysis. Two types of EV—i.e., small vesicles (SVs; <100 nm, exosome-like particles) and large vesicles (LVs; 100–400 nm, microvesicle-like particles)—were identified and found to contain a diverse group of proteins including above potential virulence factors. Although pretreatment of the parasite with two giardial lipid raft (gLR) disruptors, nystatin (27 μM) and oseltamivir (20 μM), altered the expression profiles of virulence factors in LVs and SVs, the effects were more robust in the case of SVs. To examine the potential role of rafts and vesicles in pathogenicity, Giardia-infected mice were treated with oseltamivir (1.5 and 3.0 mg/kg), and the shedding of cysts were monitored. We observed that this drug significantly reduced the parasite load in mice. Taken together, our results suggest that virulence factors partitioning in gLRs, released into the extracellular milieu via SVs and LVs, participate in spread of giardiasis and could be targeted for future drug development.

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Section: Discussionmentioning

confidence: 99%

Giardial lipid rafts share virulence factors with secreted vesicles and participate in parasitic infection in mice

Grajeda

Chatterjee

Villalobos

et al. 2022

Front. Cell. Infect. Microbiol.

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“…In pathogenic protozoa exosomes are the more prominent of the two [ 35 , 36 , 37 ]. In the case of intracellular pathogens, the ECV can be derived from either the parasite or the host cell [ 38 ].…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

“…A wide variety of metabolites, lipids, proteins, and nucleic acids has been identified as cargo in the ECV, and accordingly, a wide range of functions have been ascribed to the ECV. Such functions include roles in parasite-to-parasite communication and differentiation processes [ 35 , 36 ]. For example, exosomes promote sexual differentiation in the malaria parasite [ 40 ].…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

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Unique Endomembrane Systems and Virulence in Pathogenic Protozoa

Wiser

2021

Life

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Virulence in pathogenic protozoa is often tied to secretory processes such as the expression of adhesins on parasite surfaces or the secretion of proteases to assisted in tissue invasion and other proteins to avoid the immune system. This review is a broad overview of the endomembrane systems of pathogenic protozoa with a focus on Giardia, Trichomonas, Entamoeba, kinetoplastids, and apicomplexans. The focus is on unique features of these protozoa and how these features relate to virulence. In general, the basic elements of the endocytic and exocytic pathways are present in all protozoa. Some of these elements, especially the endosomal compartments, have been repurposed by the various species and quite often the repurposing is associated with virulence. The Apicomplexa exhibit the most unique endomembrane systems. This includes unique secretory organelles that play a central role in interactions between parasite and host and are involved in the invasion of host cells. Furthermore, as intracellular parasites, the apicomplexans extensively modify their host cells through the secretion of proteins and other material into the host cell. This includes a unique targeting motif for proteins destined for the host cell. Most notable among the apicomplexans is the malaria parasite, which extensively modifies and exports numerous proteins into the host erythrocyte. These modifications of the host erythrocyte include the formation of unique membranes and structures in the host erythrocyte cytoplasm and on the erythrocyte membrane. The transport of parasite proteins to the host erythrocyte involves several unique mechanisms and components, as well as the generation of compartments within the erythrocyte that participate in extraparasite trafficking.

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“…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].…”

Section: Current and Expected Advances In Leishmania Extracellular Vesicle Researchmentioning

confidence: 99%

Leishmania 360°: Guidelines for Exosomal Research

et al. 2021

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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.

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Unveiling the role of EVs in anaerobic parasitic protozoa

Cited by 15 publications

References 97 publications

Giardial lipid rafts share virulence factors with secreted vesicles and participate in parasitic infection in mice

Giardial lipid rafts share virulence factors with secreted vesicles and participate in parasitic infection in mice

Unique Endomembrane Systems and Virulence in Pathogenic Protozoa

Leishmania 360°: Guidelines for Exosomal Research

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