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Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4+, CD8+, and CD14+ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4+ and CD14+ EV were significantly reduced, while CD8+ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell\u2013derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host\u2013parasite interactions.<\/jats:p>","DOI":"10.3390\/pathogens14080771","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Extracellular Vesicle Release from Immune Cells in Cutaneous Leishmaniasis: Modulation by Leishmania (V.) braziliensis and Reversal by Antimonial Therapy"],"prefix":"10.3390","volume":"14","author":[{"given":"Vanessa Fernandes de Abreu","family":"Costa","sequence":"first","affiliation":[{"name":"Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"},{"name":"Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7389-2324","authenticated-orcid":false,"given":"Thaize Quiroga","family":"Chometon","sequence":"additional","affiliation":[{"name":"Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine Kelda","family":"Gomes de Castro","sequence":"additional","affiliation":[{"name":"Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7697-1618","authenticated-orcid":false,"given":"Melissa Silva Gon\u00e7alves","family":"Ponte","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"},{"name":"Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8159-0502","authenticated-orcid":false,"given":"Maria In\u00eas Fernandes","family":"Pimentel","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Research and Surveillance in Leishmaniasis, Evandro Chagas National Institute of Infectious Diseases, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Rosandiski","family":"Lyra","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Research and Surveillance in Leishmaniasis, Evandro Chagas National Institute of Infectious Diseases, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5671-3400","authenticated-orcid":false,"given":"Rienk","family":"Nieuwland","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Clinical Chemistry, Laboratory Specialized Diagnostics & Research, Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Vesicle Center, Amsterdam UMC location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro Luiz","family":"Bertho","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoparasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"},{"name":"Flow Cytometry Core Facility, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (WHO) (2025, April 24). 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