Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis

Abstract Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. The disease has an acute and a chronic phase in which approximately 30% of the chronic patients suffer from heart disease and/or gastrointestinal symptoms. The pathogenesis of the disease is multifactorial and involves th...

Full description

Bibliographic Details
Main Authors: Alberto Cornet-Gomez, Lissette Retana Moreira, Thales Kronenberger, Antonio Osuna
Format: Article
Language:English
Published: Nature Portfolio 2023-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-34820-6
_version_ 1797806736489316352
author Alberto Cornet-Gomez
Lissette Retana Moreira
Thales Kronenberger
Antonio Osuna
author_facet Alberto Cornet-Gomez
Lissette Retana Moreira
Thales Kronenberger
Antonio Osuna
author_sort Alberto Cornet-Gomez
collection DOAJ
description Abstract Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. The disease has an acute and a chronic phase in which approximately 30% of the chronic patients suffer from heart disease and/or gastrointestinal symptoms. The pathogenesis of the disease is multifactorial and involves the virulence of the strains, immunological factors and extracellular vesicles (EV) shed by the parasite which participate in cell–cell communication and evasion of the immune response. In this work, we present a transcriptomic analysis of cells stimulated with EV of the trypomastigote stage of T. cruzi. Results after EV-cell incubation revealed 322 differentially expressed genes (168 were upregulated and 154 were downregulated). In this regard, the overexpression of genes related to ubiquitin-related processes (Ube2C, SUMO1 and SUMO2) is highlighted. Moreover, the expression of Rho-GTPases (RhoA, Rac1 and Cdc42) after the interaction was analyzed, revealing a downregulation of the analyzed genes after 4 h of interaction. Finally, a protective role of EV over apoptosis is suggested, as relative values of cells in early and late apoptosis were significantly lower in EV-treated cells, which also showed increased CSNK1G1 expression. These results contribute to a better understanding of the EV-cell interaction and support the role of EV as virulence factors.
first_indexed 2024-03-13T06:11:49Z
format Article
id doaj.art-c2323972c0c44a0b8c5060cac8445e99
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-03-13T06:11:49Z
publishDate 2023-05-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-c2323972c0c44a0b8c5060cac8445e992023-06-11T11:13:18ZengNature PortfolioScientific Reports2045-23222023-05-0113111410.1038/s41598-023-34820-6Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosisAlberto Cornet-Gomez0Lissette Retana Moreira1Thales Kronenberger2Antonio Osuna3Grupo de Bioquímica y Parasitología Molecular (CTS 183), Departamento de Parasitología, Instituto de Biotecnología, Universidad de GranadaGrupo de Bioquímica y Parasitología Molecular (CTS 183), Departamento de Parasitología, Instituto de Biotecnología, Universidad de GranadaInstitute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery (TüCAD2), Eberhard Karls University TübingenGrupo de Bioquímica y Parasitología Molecular (CTS 183), Departamento de Parasitología, Instituto de Biotecnología, Universidad de GranadaAbstract Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. The disease has an acute and a chronic phase in which approximately 30% of the chronic patients suffer from heart disease and/or gastrointestinal symptoms. The pathogenesis of the disease is multifactorial and involves the virulence of the strains, immunological factors and extracellular vesicles (EV) shed by the parasite which participate in cell–cell communication and evasion of the immune response. In this work, we present a transcriptomic analysis of cells stimulated with EV of the trypomastigote stage of T. cruzi. Results after EV-cell incubation revealed 322 differentially expressed genes (168 were upregulated and 154 were downregulated). In this regard, the overexpression of genes related to ubiquitin-related processes (Ube2C, SUMO1 and SUMO2) is highlighted. Moreover, the expression of Rho-GTPases (RhoA, Rac1 and Cdc42) after the interaction was analyzed, revealing a downregulation of the analyzed genes after 4 h of interaction. Finally, a protective role of EV over apoptosis is suggested, as relative values of cells in early and late apoptosis were significantly lower in EV-treated cells, which also showed increased CSNK1G1 expression. These results contribute to a better understanding of the EV-cell interaction and support the role of EV as virulence factors.https://doi.org/10.1038/s41598-023-34820-6
spellingShingle Alberto Cornet-Gomez
Lissette Retana Moreira
Thales Kronenberger
Antonio Osuna
Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis
Scientific Reports
title Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis
title_full Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis
title_fullStr Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis
title_full_unstemmed Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis
title_short Extracellular vesicles of trypomastigotes of Trypanosoma cruzi induce changes in ubiquitin-related processes, cell-signaling pathways and apoptosis
title_sort extracellular vesicles of trypomastigotes of trypanosoma cruzi induce changes in ubiquitin related processes cell signaling pathways and apoptosis
url https://doi.org/10.1038/s41598-023-34820-6
work_keys_str_mv AT albertocornetgomez extracellularvesiclesoftrypomastigotesoftrypanosomacruziinducechangesinubiquitinrelatedprocessescellsignalingpathwaysandapoptosis
AT lissetteretanamoreira extracellularvesiclesoftrypomastigotesoftrypanosomacruziinducechangesinubiquitinrelatedprocessescellsignalingpathwaysandapoptosis
AT thaleskronenberger extracellularvesiclesoftrypomastigotesoftrypanosomacruziinducechangesinubiquitinrelatedprocessescellsignalingpathwaysandapoptosis
AT antonioosuna extracellularvesiclesoftrypomastigotesoftrypanosomacruziinducechangesinubiquitinrelatedprocessescellsignalingpathwaysandapoptosis