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The endothelial integrity and function might be compromised due to various causes, including infection by Toxoplasma gondii, leading to an endothelial dysfunction. Toxoplasma gondii is an Apicomplexa parasite that infects a broad range of animals, including humans. This parasite can invade all nucleated cells, as well as endothelial cells. The interaction between this protozoan and endothelial cells can be mediated by different molecules, such as extracellular vesicles (EVs), which may either favor or hinder the infectious process. To investigate this interaction, we evaluated the infection of T. gondii on human brain microvascular endothelial cells (HBMEC) and human umbilical vein endothelial cells (HUVEC), in addition to assessing transcriptional changes. We also featured the EVs secreted by T. gondii and by infected and non-infected HBMEC and HUVEC. Finally, we evaluated the infection of cells stimulated with EVs of parasitic or cellular origin. Our results demonstrated that HUVEC not only exhibit a higher infection rate than HBMEC but also display a more pro-inflammatory transcriptional profile, with increased expression of interleukin-6 (IL6), interleukin-8 (IL8), and monocyte chemotactic protein-1 (MCP1) following infection. Additionally, we observed few differences in the concentration, distribution, and morphology of EVs secreted by both cell types, although their properties in modulating infection varied significantly. When cells were EVs stimulated, EVs from T. gondii promoted an increase in the HBMEC infection, EVs from infected or uninfected HBMEC reduced the infection, whereas EVs from HUVEC had no effect on the infectious process. In conclusion, our data indicate that T. gondii infection induces distinct changes in different endothelial cell types, and EVs from these cells can contribute to the resolution of the infection.<\/jats:p>","DOI":"10.3390\/ijms26062640","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:07:51Z","timestamp":1741957671000},"page":"2640","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Human Brain Endothelial Cell-Derived Extracellular Vesicles Reduce Toxoplasma gondii Infection In Vitro in Human Brain and Umbilical Cord Vein Endothelial Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9616-0927","authenticated-orcid":false,"given":"Luiz Fernando Cardoso","family":"Garcia","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Apicomplexa, Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ-PR), Curitiba 81350-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-7328","authenticated-orcid":false,"given":"Victoria Cruz","family":"Cavalari","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Apicomplexa, Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ-PR), Curitiba 81350-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8976-2647","authenticated-orcid":false,"given":"Pryscilla Fanini","family":"Wowk","sequence":"additional","affiliation":[{"name":"Grupo de Imunologia Molecular, Celular e Intelig\u00eancia Artificial, Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ-PR), Curitiba 81350-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6406-2057","authenticated-orcid":false,"given":"Letusa","family":"Albrecht","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Pesquisa em Apicomplexa, Instituto Carlos Chagas, Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ-PR), Curitiba 81350-010, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","first-page":"625","article-title":"Article Fate Tracing Reveals the Endothelial Origin of Hematopoietic Stem Cells","volume":"3","author":"Zovein","year":"2008","journal-title":"Stem Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1111\/jcmm.13088","article-title":"Extracellular histones disarrange vasoactive mediators release through a COX-NOS interaction in human endothelial cells","volume":"21","author":"Hermenegildo","year":"2017","journal-title":"J. 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