Immunomodulatory Properties of Leishmania Extracellular Vesicles During Host-Parasite Interaction: Differential Activation of TLRs and NF-κB Translocation by Dermotropic and Viscerotropic Species

Nogueira, Paula Monalisa; Menezes-Neto, Armando de; Borges, Valéria M.; Descoteaux, Albert; Torrecilhas, Ana Claúdia; Xander, Patrícia; Revach, Or‐Yam; Regev‐Rudzki, Neta; Soares, Rodrigo Pedro

doi:10.3389/fcimb.2020.00380

Cited by 30 publications

(48 citation statements)

References 34 publications

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“…Using GP63-deficient Leishmania major parasites, we demonstrated that the absence of this virulence factor, which is greatly enriched in wild-type L. major exosomes, was almost completely abrogating their capacity to modulate host immune response comparatively to its wild-type counterpart (Hassani et al, 2014). This is different from L. infantum LPG1 -/-mutants, where the lack of this glycoconjugate did not affect NO and cytokine induction by its EVs (Nogueira et al, 2020). This further demonstrates the critical role played by Leishmania virulence factors enriched in leishmanial exosomes.…”

Section: Leishmania Evsmentioning

confidence: 78%

“…IL-10, IL-4) and exacerbate pathology ( Silverman et al, 2010b ). More recently, EVs from New-World, dermotropic L. amazonensis were found to be more pro-inflammatory, triggering the production of NO, IL-6 and TNF-α in a TLR4/TLR2/NF-κB-dependent fashion ( Nogueira et al, 2020 ). On the other hand, in the same study, EVs from L. infantum and L. braziliensis were not able to induce significant levels of those cytokines ( Nogueira et al, 2020 ) but induced IL-10 ( Castelli et al, 2019 ).…”

Section: Biogenesis Of Evs In Trypanosomesmentioning

confidence: 99%

“…More recently, EVs from New-World, dermotropic L. amazonensis were found to be more pro-inflammatory, triggering the production of NO, IL-6 and TNF-α in a TLR4/TLR2/NF-κB-dependent fashion ( Nogueira et al, 2020 ). On the other hand, in the same study, EVs from L. infantum and L. braziliensis were not able to induce significant levels of those cytokines ( Nogueira et al, 2020 ) but induced IL-10 ( Castelli et al, 2019 ). Although this study was in vitro , in vivo studies with L. amazonensis EVs in B-1 cells and L. infantum confirmed their pro-inflammatory activity ( Barbosa et al, 2018 ; Perez-Cabezas et al, 2019 ; Toledo et al, 2020 ).…”

Section: Biogenesis Of Evs In Trypanosomesmentioning

confidence: 99%

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Extracellular Vesicles in Trypanosomatids: Host Cell Communication

Torrecilhas

Soares

Schenkman

et al. 2020

Front. Cell. Infect. Microbiol.

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Trypanosoma cruzi, Trypanosoma brucei and Leishmania (Trypanosomatidae: Kinetoplastida) are parasitic protozoan causing Chagas disease, African Trypanosomiasis and Leishmaniases worldwide. They are vector borne diseases transmitted by triatomine bugs, Tsetse fly, and sand flies, respectively. Those diseases cause enormous economic losses and morbidity affecting not only rural and poverty areas but are also spreading to urban areas. During the parasite-host interaction, those organisms release extracellular vesicles (EVs) that are crucial for the immunomodulatory events triggered by the parasites. EVs are involved in cell-cell communication and can act as important pro-inflammatory mediators. Therefore, interface between EVs and host immune responses are crucial for the immunopathological events that those diseases exhibit. Additionally, EVs from these organisms have a role in the invertebrate hosts digestive tracts prior to parasite transmission. This review summarizes the available data on how EVs from those medically important trypanosomatids affect their interaction with vertebrate and invertebrate hosts.

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Section: Leishmania Evsmentioning

confidence: 78%

Section: Biogenesis Of Evs In Trypanosomesmentioning

confidence: 99%

Section: Biogenesis Of Evs In Trypanosomesmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular Vesicles in Trypanosomatids: Host Cell Communication

Torrecilhas

Soares

Schenkman

et al. 2020

Front. Cell. Infect. Microbiol.

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“…Murine macrophage assays were evaluated through nonparametric Kruskal–Wallis test followed by Dunn's post hoc test for multiple comparisons among groups (lines above bars). Student's t test was used to compare each sample and letters above bars indicate statistical differences ( p < .05; Nogueira et al, 2020).…”

Section: Methodsmentioning

confidence: 99%

“…In other protozoans including Leishmania and Trypanosoma cruzi , EVs shed by parasitic cells are involved in the modulation of immune responses exhibiting inter and intraspecies variations (Atayde et al, 2016; Barbosa et al, 2018; Nogueira et al, 2015). In the case of T. cruzi and Leishmania , innate immune responses depend on TLR2 and TLR4 resulting in the induction of several cytokines and nuclear factor kappa B (NF‐kB) translocation (Barbosa et al, 2018; Nogueira et al, 2020; Silverman & Reiner, 2011; Toledo et al, 2020). In Acanthamoeba , in vivo and in vitro studies have addressed this type of interaction with the innate immune compartment but using trophozoites.…”

Section: Introductionmentioning

confidence: 99%

Distinct immunomodulatory properties of extracellular vesicles released by different strains of Acanthamoeba

Costa

Chagas

Menezes-Neto

et al. 2021

Cell Biology International

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Free living amoeba of the genus Acanthamoeba are opportunist protozoan involved in corneal, systemic, and encephalic infections in humans. Most of the mechanisms underlying intraspecies variations and pathogenicity are still unknown. Recently, the release of extracellular vesicles (EVs) by Acanthamoeba was reported. However, comparative characterization of EVs from distinct strains is not available. The aim of this study was to evaluate EVs produced by Acanthamoeba from different genotypes, comparing their proteases profile and immunomodulatory properties. EVs from four environmental or clinical strains (genotypes T1, T2, T4, and T11) were obtained by ultracentrifugation, quantitated by nanoparticle tracking analysis and analyzed by scanning and transmission electron microscopy. Proteases profile was determined by zymography and functional properties of EVs (measure of nitrite and cytokine production) were determined after peritoneal macrophage stimulation. Despite their genotype, all strains released EVs and no differences in size and/or concentration were detected. EVs exhibited a predominant activity of serine proteases (pH 7.4 and 3.5), with higher intensity in T4 and T1 strains. EVs from the environmental, nonpathogenic T11 strain exhibited a more proinflammatory profile, inducing higher levels of Nitrite, tumor necrosis factor alpha and interleukin‐6 via TLR4/TLR2 than those strains with pathogenic traits (T4, T1, and T2). Preincubation with EVs treated with protease inhibitors or heating drastically decreased nitrite concentration production in macrophages. Those data suggest that immunomodulatory effects of EVs may reflect their pathogenic potential depending on the Acanthamoeba strains and are dependent on protease integrity.

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Guidelines for the purification and characterization of extracellular vesicles of parasites

Fernandez‐Becerra,

Xander,

Alfandari

et al. 2023

J of Extracellular Bio

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Parasites are responsible for the most neglected tropical diseases, affecting over a billion people worldwide (WHO, 2015) and accounting for billions of cases a year and responsible for several millions of deaths. Research on extracellular vesicles (EVs) has increased in recent years and demonstrated that EVs shed by pathogenic parasites interact with host cells playing an important role in the parasite's survival, such as facilitation of infection, immunomodulation, parasite adaptation to the host environment and the transfer of drug resistance factors. Thus, EVs released by parasites mediate parasite‐parasite and parasite‐host intercellular communication. In addition, they are being explored as biomarkers of asymptomatic infections and disease prognosis after drug treatment. However, most current protocols used for the isolation, size determination, quantification and characterization of molecular cargo of EVs lack greater rigor, standardization, and adequate quality controls to certify the enrichment or purity of the ensuing bioproducts. We are now initiating major guidelines based on the evolution of collective knowledge in recent years. The main points covered in this position paper are methods for the isolation and molecular characterization of EVs obtained from parasite‐infected cell cultures, experimental animals, and patients. The guideline also includes a discussion of suggested protocols and functional assays in host cells

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Immunomodulatory Properties of Leishmania Extracellular Vesicles During Host-Parasite Interaction: Differential Activation of TLRs and NF-κB Translocation by Dermotropic and Viscerotropic Species

Cited by 30 publications

References 34 publications

Extracellular Vesicles in Trypanosomatids: Host Cell Communication

Extracellular Vesicles in Trypanosomatids: Host Cell Communication

Distinct immunomodulatory properties of extracellular vesicles released by different strains of Acanthamoeba

Guidelines for the purification and characterization of extracellular vesicles of parasites

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