Extracellular vesicles from Trypanosoma cruzi-dendritic cell interaction show modulatory properties and confer resistance to lethal infection as a cell-free based therapy strategy

Gutierrez, Brenda C.; Ancarola, María Eugenia; Volpato-Rossi, Izadora; Marcilla, Antonio; Ramirez, Marcel I.; Rosenzvit, Mara Cecília; Cucher, Marcela Alejandra; Poncini, Carolina Verónica

doi:10.3389/fcimb.2022.980817

Cited by 13 publications

(8 citation statements)

References 75 publications

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“…Recently, EVs have gained attention in translational applications, from the discovery of biomarkers for diseases, to their roles in drug delivery systems. For example, the work by Gutierrez et al (2022) [ 28 ] showed that EVs derived from the interaction of T. cruzi trypomastigotes with dendritic cells conferred protection to animals challenged with lethal infection by T. cruzi . Furthermore, the potential of EVs present in the serum of S. aureus osteomyelitis patients to facilitate the diagnosis has already been discussed [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

An Improved Method to Enrich Large Extracellular Vesicles Derived from Giardia intestinalis through Differential Centrifugation

Sana,

Rossi,

Sabatke

et al. 2023

Life

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Giardia intestinalis is a flagellated unicellular protozoan that colonizes the small intestine, causing the diarrheal disease called giardiasis. The production of extracellular vesicles (EVs) by G. intestinalis and the role of these EVs in the parasite’s interaction with the host have been described. According to biogenesis, EVs are grouped mainly into large (microvesicles—derived from the plasma membrane) and small (exosomes—derived from multivesicular bodies). Populations of EVs are heterogeneous, and improved methods to separate and study them are needed to understand their roles in cell physiology and pathologies. This work aimed to enrich the large extracellular vesicles (LEVs) of G. intestinalis in order to better understand the roles of these vesicles in the interaction of the parasite with the host. To achieve the enrichment of the LEVs, we have modified our previously described method and compared it by protein dosage and using Nano tracking analysis. Giardia intestinalis vesiculation was induced by incubation in a TYI-S-33 medium without serum, to which 1 mM of CaCl2 was added at 37 °C for 1 h. Then, the supernatant was centrifuged at 15,000× g for 1 h (15 K 1 h pellet), 15,000× g for 4 h (15 K 4 h pellet) and 100,000× g for 1.5 h (100 K 1h30 pellet). The pellet (containing EVs) was resuspended in 1× PBS and stored at 4 °C for later analysis. The EVs were quantified based on their protein concentrations using the Pierce BCA assay, and by nanoparticle tracking analysis (NTA), which reports the concentration and size distribution of the particles. The NTA showed that direct ultracentrifugation at 100,000× g for 1.5 h and centrifugation at 15,000× g for 4 h concentrated more EVs compared to centrifugation at 15,000× g for 1 h. Additionally, it revealed that centrifugation at 15,000× g 4 h was able to concentrate at the same particle concentration levels as a direct ultracentrifugation at 100,000× g for 1.5 h. As for the enrichment of LEVs, the NTA has shown a higher concentration of LEVs in direct ultracentrifugation at 100,000× g for 1.5 h, and in centrifugation at 15,000× g for 4 h, compared to centrifugation at 15,000× g for 1 h. Our results have shown that the most used method at 15,000× g for 1 h is not enough to obtain a representative population of large EVs, and we suggest that LEVs released by G. intestinalis can be better enriched by direct ultracentrifugation at 100,000× g for 1.5 h, or by centrifugation at 15,000× g for 4 h.

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Section: Discussionmentioning

confidence: 99%

An Improved Method to Enrich Large Extracellular Vesicles Derived from Giardia intestinalis through Differential Centrifugation

Sana,

Rossi,

Sabatke

et al. 2023

Life

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“…While these proteins have not yet shown promise as vaccine candidates, the mucin‐like‐associated surface protein (MASP) family, a virulence factor involved in host‐cell invasion, has shown the ability to induce a humoral and cellular response and reduce parasite load when used in immunisation of mice [50]. Recently, a single dose of T. cruzi ‐pulsed dendritic cell (DC) EVs has been shown to induce a protective cellular immune response, reduce parasite load and increase survival of mice after infection with a lethal strain [51]. However, this strategy using DCs is limited by its high cost and the challenges of delivering the antigen effectively.…”

Section: Can Extracellular Vesicles Aid Vaccine Development?mentioning

confidence: 99%

Extracellular Vesicles: Translational Agenda Questions for Three Protozoan Parasites

Tandoh,

Ibarra‐Meneses,

Langlais

et al. 2024

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The protozoan parasites Plasmodium falciparum, Leishmania spp. and Trypanosoma cruzi continue to exert a significant toll on the disease landscape of the human population in sub‐Saharan Africa and Latin America. Control measures have helped reduce the burden of their respective diseases—malaria, leishmaniasis and Chagas disease—in endemic regions. However, the need for new drugs, innovative vaccination strategies and molecular markers of disease severity and outcomes has emerged because of developing antimicrobial drug resistance, comparatively inadequate or absent vaccines, and a lack of trustworthy markers of morbid outcomes. Extracellular vesicles (EVs) have been widely reported to play a role in the biology and pathogenicity of P. falciparum, Leishmania spp. and T. cruzi ever since they were discovered. EVs are secreted by a yet to be fully understood mechanism in protozoans into the extracellular milieu and carry a cargo of diverse molecules that reflect the originator cell's metabolic state. Although our understanding of the biogenesis and function of EVs continues to deepen, the question of how EVs in P. falciparum, Leishmania spp. and T. cruzi can serve as targets for a translational agenda into clinical and public health interventions is yet to be fully explored. Here, as a consortium of protozoan researchers, we outline a plan for future researchers and pose three questions to direct an EV's translational agenda in P. falciparum, Leishmania spp. and T. cruzi. We opine that in the long term, executing this blueprint will help bridge the current unmet needs of these medically important protozoan diseases in sub‐Saharan Africa and Latin America.

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“…For example, it was found that sera from patients with CD was immunoreactive to proteins present in EVs, placing these particles as a possible biomarker of CD [138]. Regarding vaccines, Gutierrez et al [143] showed that EVs from the interaction between blood trypomastigotes and bone marrow-derived DCs confer partial protection in animals challenged with lethal T. cruzi infection. These results, together with reports on other pathogens such as Toxoplasma gondii [144,145], Eimeria spp.…”

Section: Preference or Restriction To A Certain Host Tissue? Factors ...mentioning

confidence: 99%

The End Justifies the Means: Chagas Disease from a Perspective of the Host–Trypanosoma cruzi Interaction

Rossi,

de Souza,

Ramirez

2024

Life

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The neglected Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi. Despite CD dispersion throughout the world, it prevails in tropical areas affecting mainly poor communities, causing devastating health, social and economic consequences. Clinically, CD is marked by a mildly symptomatic acute phase, and a chronic phase characterized by cardiac and/or digestive complications. Current treatment for CD relies on medications with strong side effects and reduced effectiveness. The complex interaction between the parasite and the host outlines the etiology and progression of CD. The unique characteristics and high adaptability of T. cruzi, its mechanisms of persistence, and evasion of the immune system seem to influence the course of the disease. Despite the efforts to uncover the pathology of CD, there are many gaps in understanding how it is established and reaches chronicity. Also, the lack of effective treatments and protective vaccines constitute challenges for public health. Here, we explain the background in which CD is established, from the peculiarities of T. cruzi molecular biology to the development of the host’s immune response leading to the pathophysiology of CD. We also discuss the state of the art of treatments for CD and current challenges in basic and applied science.

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Extracellular vesicles from Trypanosoma cruzi-dendritic cell interaction show modulatory properties and confer resistance to lethal infection as a cell-free based therapy strategy

Cited by 13 publications

References 75 publications

An Improved Method to Enrich Large Extracellular Vesicles Derived from Giardia intestinalis through Differential Centrifugation

An Improved Method to Enrich Large Extracellular Vesicles Derived from Giardia intestinalis through Differential Centrifugation

Extracellular Vesicles: Translational Agenda Questions for Three Protozoan Parasites

The End Justifies the Means: Chagas Disease from a Perspective of the Host–Trypanosoma cruzi Interaction

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