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constitute a family of parasitic protozoa that cause significant human and veterinary diseases that are classified as neglected zoonotic diseases (NZDs). In a rapidly evolving world, these diseases have the potential to become a world health problem no longer solely associated with low-income countries. Therefore, the development of new strategies to control and restrain the dissemination of trypanosomatids is imperative. Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed vesicles released by prokaryotic and eukaryotic cells. They can be found in diverse body fluids that carry biologically active molecules, including proteins, nucleic acids, lipids, and carbohydrates. EVs participate in cell-to-cell communication by delivering their cargo content to recipient cells. Thus, EVs play a role in regulating normal physiological processes, including immune surveillance and tissue repair, as well as being involved in pathological conditions, like cancer. In recent years, EVs have attracted significant attention from the scientific community, mainly due to their immune regulatory properties. Therefore, this review examines the role played by trypanosomatid-derived EVs in leishmaniases and trypanosomiasis, highlighting their biological role in host\u2013parasite communication and exploring their potential future applications in controlling NZDs, especially those caused by trypanosomatids.<\/jats:p>","DOI":"10.3390\/ijms26094302","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T09:16:12Z","timestamp":1746090972000},"page":"4302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Extracellular Vesicles Derived from Trypanosomatids: The Key to Decoding Host\u2013Parasite Communication"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4261-3879","authenticated-orcid":false,"given":"Armanda","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6504-4384","authenticated-orcid":false,"given":"Juliana In\u00eas","family":"Weber","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0585-5050","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Dur\u00e3es-Oliveira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6948-9823","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Moreno","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008 Lisboa, Portugal"}]},{"given":"Micheli","family":"Ferla","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-9124","authenticated-orcid":false,"given":"Maria de","family":"Aires Pereira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008 Lisboa, Portugal"},{"name":"CERNAS-IPV Research Centre, Instituto Polit\u00e9cnico de Viseu, Campus Polit\u00e9cnico, Repeses, 3504-510 Viseu, Portugal"}]},{"given":"Ana","family":"Val\u00e9rio-Bolas","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8695-7019","authenticated-orcid":false,"given":"Bruna Eug\u00eania de","family":"Freitas","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, 1349-008 Lisboa, Portugal"},{"name":"Instituto de Ci\u00eancias Biol\u00f3gicas, ICB, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4569-2114","authenticated-orcid":false,"given":"Telmo","family":"Nunes","sequence":"additional","affiliation":[{"name":"Microscopy Center, Faculty of Sciences, University of Lisbon-FCUL-BioISI Ce3CE, 1749-016 Lisboa, Portugal"}]},{"given":"Wilson T.","family":"Antunes","sequence":"additional","affiliation":[{"name":"Instituto Universit\u00e1rio Militar (IUM), Centro de Investiga\u00e7\u00e3o, Desenvolvimento e Inova\u00e7\u00e3o da Academia Militar (CINAMIL), Unidade Militar Laboratorial de Defesa Biol\u00f3gica e Qu\u00edmica (UMLDBQ), 1849-012 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-4679","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Alexandre-Pires","sequence":"additional","affiliation":[{"name":"CIISA, Centre for 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Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023). 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