Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes

All extracellular forms of Trypanosoma cruzi, the causative agent of Chagas disease, release extracellular vesicles (EVs) containing major surface molecules of the parasite. EV release depends on several mechanisms (internal and external). However, most of the environmental conditions affecting this...

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Main Authors: Camilla Ioshida Vasconcelos, A Cronemberger-Andrade, Normanda Souza-Melo, Juliana Terzi Maricato, Patrícia Xander, Wagner Luiz Batista, Rodrigo Pedro Soares, Sergio Schenkman, Ana Claudia Torrecilhas
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/2939693
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author Camilla Ioshida Vasconcelos
A Cronemberger-Andrade
Normanda Souza-Melo
Juliana Terzi Maricato
Patrícia Xander
Wagner Luiz Batista
Rodrigo Pedro Soares
Sergio Schenkman
Ana Claudia Torrecilhas
author_facet Camilla Ioshida Vasconcelos
A Cronemberger-Andrade
Normanda Souza-Melo
Juliana Terzi Maricato
Patrícia Xander
Wagner Luiz Batista
Rodrigo Pedro Soares
Sergio Schenkman
Ana Claudia Torrecilhas
author_sort Camilla Ioshida Vasconcelos
collection DOAJ
description All extracellular forms of Trypanosoma cruzi, the causative agent of Chagas disease, release extracellular vesicles (EVs) containing major surface molecules of the parasite. EV release depends on several mechanisms (internal and external). However, most of the environmental conditions affecting this phenomenon are still unknown. In this work, we evaluated EV release under different stress conditions and their ability to be internalized by the parasites. In addition, we investigated whether the release conditions would affect their immunomodulatory properties in preactivated bone marrow-derived macrophages (BMDM). Sodium azide and methyl-cyclo-β-dextrin (CDB) reduced EV release, indicating that this phenomenon relies on membrane organization. EV release was increased at low temperatures (4°C) and acidic conditions (pH 5.0). Under this pH, trypomastigotes differentiated into amastigotes. EVs are rapidly liberated and reabsorbed by the trypomastigotes in a concentration-dependent manner. Nitrosative stress caused by sodium nitrite in acid medium or S-nitrosoglutathione also stimulated the secretion of EVs. EVs released under all stress conditions also maintained their proinflammatory activity and increased the expression of iNOS, Arg 1, IL-12, and IL-23 genes in IFN-γ and LPS preactivated BMDM. In conclusion, our results suggest a budding mechanism of release, dependent on the membrane structure and parasite integrity. Stress conditions did not affect functional properties of EVs during interaction with host cells. EV release variations under stress conditions may be a physiological response against environmental changes.
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spelling doaj-art-4ccb2f28e5df424aaafcb2d90d6471ae2025-08-20T02:38:39ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/29396932939693Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi TrypomastigotesCamilla Ioshida Vasconcelos0A Cronemberger-Andrade1Normanda Souza-Melo2Juliana Terzi Maricato3Patrícia Xander4Wagner Luiz Batista5Rodrigo Pedro Soares6Sergio Schenkman7Ana Claudia Torrecilhas8Departamento de Ciências Farmacêuticas, UNIFESP, Rua São Nicolau, 210, 09913-030, Diadema, São Paulo, BrazilCell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), 5020 Salzburg, AustriaDepartamento de Microbiologia, Imunologia e Parasitologia, UNIFESP, Rua Pedro de Toledo, 669, 04039-032 São Paulo, BrazilDepartamento de Microbiologia, Imunologia e Parasitologia, UNIFESP, Rua Botucatu, 862, 04023-062 São Paulo, BrazilDepartamento de Ciências Farmacêuticas, UNIFESP, Rua São Nicolau, 210, 09913-030, Diadema, São Paulo, BrazilDepartamento de Ciências Farmacêuticas, UNIFESP, Rua São Nicolau, 210, 09913-030, Diadema, São Paulo, BrazilInstituto René Rachou/FIOCRUZ-MG, Av. Augusto de Lima, 1715, 30190-009 Belo Horizonte, Minas Gerais, BrazilDepartamento de Microbiologia, Imunologia e Parasitologia, UNIFESP, Rua Pedro de Toledo, 669, 04039-032 São Paulo, BrazilDepartamento de Ciências Farmacêuticas, UNIFESP, Rua São Nicolau, 210, 09913-030, Diadema, São Paulo, BrazilAll extracellular forms of Trypanosoma cruzi, the causative agent of Chagas disease, release extracellular vesicles (EVs) containing major surface molecules of the parasite. EV release depends on several mechanisms (internal and external). However, most of the environmental conditions affecting this phenomenon are still unknown. In this work, we evaluated EV release under different stress conditions and their ability to be internalized by the parasites. In addition, we investigated whether the release conditions would affect their immunomodulatory properties in preactivated bone marrow-derived macrophages (BMDM). Sodium azide and methyl-cyclo-β-dextrin (CDB) reduced EV release, indicating that this phenomenon relies on membrane organization. EV release was increased at low temperatures (4°C) and acidic conditions (pH 5.0). Under this pH, trypomastigotes differentiated into amastigotes. EVs are rapidly liberated and reabsorbed by the trypomastigotes in a concentration-dependent manner. Nitrosative stress caused by sodium nitrite in acid medium or S-nitrosoglutathione also stimulated the secretion of EVs. EVs released under all stress conditions also maintained their proinflammatory activity and increased the expression of iNOS, Arg 1, IL-12, and IL-23 genes in IFN-γ and LPS preactivated BMDM. In conclusion, our results suggest a budding mechanism of release, dependent on the membrane structure and parasite integrity. Stress conditions did not affect functional properties of EVs during interaction with host cells. EV release variations under stress conditions may be a physiological response against environmental changes.http://dx.doi.org/10.1155/2021/2939693
spellingShingle Camilla Ioshida Vasconcelos
A Cronemberger-Andrade
Normanda Souza-Melo
Juliana Terzi Maricato
Patrícia Xander
Wagner Luiz Batista
Rodrigo Pedro Soares
Sergio Schenkman
Ana Claudia Torrecilhas
Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes
Journal of Immunology Research
title Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes
title_full Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes
title_fullStr Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes
title_full_unstemmed Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes
title_short Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes
title_sort stress induces release of extracellular vesicles by trypanosoma cruzi trypomastigotes
url http://dx.doi.org/10.1155/2021/2939693
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