Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes

Author(s)

Vasconcelos, Camilla Ioshida ^[1] ; Cronemberger-Andrade, A. ^[2] ; Souza-Melo, Normanda ^[3] ; Maricato, Juliana Terzi ^[4] ; Xander, Patricia ^[1] ; Batista, Wagner Luiz ^[1] ; Soares, Rodrigo Pedro ^[5] ; Schenkman, Sergio ^[3] ; Torrecilhas, Ana Claudia ^[1]

Affiliation

^[1] UNIFESP, Dept Ciencias Farmaceut, Rua Sao Nicolau 210, BR-09913030 Diadema, SP - Brazil

^[2] Paracelsus Med Univ PMU, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, Cell Therapy Inst, A-5020 Salzburg - Austria

^[3] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Rua Botucatu 862, BR-04023062 Sao Paulo - Brazil

^[5] Inst Rene Rachou FIOCRUZ MG, Av Augusto de Lima 1715, BR-30190009 Belo Horizonte, MG - Brazil

• Document type: Journal article
• Source: JOURNAL OF IMMUNOLOGY RESEARCH; v. 2021, SEP 24 2021.
• Web of Science Citations: 0

Abstract

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-beta-dextrin (CDB) reduced EV release, indicating that this phenomenon relies on membrane organization. EV release was increased at low temperatures (4 degrees 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-gamma 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. (AU)

• FAPESP's process: 19/15909-0 - Studying mechanisms of extracellular vesicle secretion by protozoan parasites
• Grantee: Sergio Schenkman
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/07870-4 - Mechanisms of trypanosomatid adaptation to hosts through the control of transcription, protein synthesis and secretion of extracellular vesicles
• Grantee: Ana Claudia Trocoli Torrecilhas
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/02416-0 - Protein secretion in Trypanosoma
• Grantee: Normanda Souza Melo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral