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The results obtained by several groups indicated compositional variations in EVs generated by distinct types of <jats:italic>T. cruzi<\/jats:italic>. Nonetheless, few studies have characterized EVs derived from metacyclic trypomastigotes (MT), the form that develops in the vector and infects vertebrate hosts. This study aimed to characterize and compare EVs extracted from MTs of two <jats:italic>T. cruzi<\/jats:italic> parasite strains belonging to distinct groups with varying infectivity patterns. We examined the nature of these EVs and their influence on parasite\u2010host interactions and host immune responses. Our findings demonstrated that EVs from G and Y strains showed no significant size differences; nonetheless, they exhibited variations in protein composition as shown by proteomic analysis, atomic force microscopy, and immunoenzymatic assays, including alterations in the presence of virulence factors. EVs from both strains interacted with and were taken up by human THP\u20101 monocytes, resulting in NF\u2010\u03baB activation. The EVs release from Y strain increase in the mRNA levels of RANTES, TNF\u2010alpha, and IFN\u2010beta, while inducing a similar nitric oxide (NO) increase relative to control cells. EVs from both strains also increased host cell invasion, however, EVs from the Y further increased the number of intracellular parasites. These results suggest that the infectivity of various strains by insect\u2010derived forms correlates with EV secretion via the control of the host immune response, potentially leading to distinct infection patterns.<\/jats:p>","DOI":"10.1002\/cbin.70043","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T08:07:09Z","timestamp":1748851629000},"page":"1141-1162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>Trypanosoma Cruzi<\/i> G and Y Strains' Metacyclic Trypomastigote Sheds Extracellular Vesicles and Trigger Host\u2010Cell Communication"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9885-3818","authenticated-orcid":false,"given":"Paula","family":"Meneghetti","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Imunologia Celular e Bioqu\u00edmica de Fungos e Protozo\u00e1rios, Departamento de Ci\u00eancias Farmac\u00eauticas Instituto de Ci\u00eancias Ambientais, Qu\u00edmicas e Farmac\u00eauticas, Universidade Federal de S\u00e3o Paulo (UNIFESP) S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6167-2156","authenticated-orcid":false,"given":"Ewa","family":"Kozela","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences Faculty of Biochemistry, Weizmann Institute of Science Rehovot Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Alfandari","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences Faculty of Biochemistry, Weizmann Institute of Science Rehovot Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6612-4936","authenticated-orcid":false,"given":"Paula Abou","family":"Karam","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences Faculty of Biochemistry, Weizmann Institute of Science Rehovot Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3059-181X","authenticated-orcid":false,"given":"Ziv","family":"Porat","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Life Sciences Core Facilities, Weizmann Institute of Science Rehovot Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6329-6449","authenticated-orcid":false,"given":"Patricia","family":"Xander","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunologia Celular e Bioqu\u00edmica de Fungos e Protozo\u00e1rios, Departamento de Ci\u00eancias Farmac\u00eauticas Instituto de Ci\u00eancias Ambientais, Qu\u00edmicas e Farmac\u00eauticas, Universidade Federal de S\u00e3o Paulo (UNIFESP) S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7252-0193","authenticated-orcid":false,"given":"Neta","family":"Regev\u2010Rudzki","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Sciences Faculty of Biochemistry, Weizmann Institute of Science Rehovot Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9353-8480","authenticated-orcid":false,"given":"Sergio","family":"Schenkman","sequence":"additional","affiliation":[{"name":"Departamento de Microbiologia Imunologia e Parasitologia, UNIFESP S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5724-2199","authenticated-orcid":false,"given":"Ana Claudia","family":"Torrecilhas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunologia Celular e Bioqu\u00edmica de Fungos e Protozo\u00e1rios, Departamento de Ci\u00eancias Farmac\u00eauticas Instituto de Ci\u00eancias Ambientais, Qu\u00edmicas e Farmac\u00eauticas, Universidade Federal de S\u00e3o Paulo (UNIFESP) S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202254755"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26041544"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr300947g"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-6-127"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2014.02.012"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004792"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797"},{"key":"e_1_2_10_9_1","first-page":"93","article-title":"Growth and Differentiation in Trypanosoma Cruzi. 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