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In Brazil this infection is caused by Leishmania (Leishmania) infantum. Extracellular vesicles (EVs) released by Leishmania species have different functions like the modulation of host immune systems and inflammatory responses, among others. This study evaluated the participation of EVs from L. (L.) infantum (Leish-EVs) in recognition of the humoral and cellular immune response of hosts with VL. Promastigotes were cultivated in 199 medium and, in the log phase of growth, they were centrifuged, washed, resus-pended in RPMI medium, and incubated for 2 to 24 h, at 25 \u00b0C or 37 \u00b0C to release Leish-EVs. This dynamic was evaluated using transmission (TEM) and scanning (SEM) electron microscopies, as well as nanoparticle tracking analysis (NTA). The results suggested that parasite penetration in mammal macrophages requires more Leish-EVs than those living in insect vectors, since promastigotes incubated at 37 \u00b0C released more Leish-EVs than those incubated at 25 \u00b0C. Infected THP-1 cells produced high EV concentration (THP-1 cells-EVs) when compared with those from the control group. The same results were obtained when THP-1 cells were treated with Leish-EVs or a crude Leishmania antigen. These data indicated that host\u2013EV concentrations could be used to distinguish infected from uninfected hosts. THP-1 cells treated with Leish-EVs expressed more IL-12 than control THP-1 cells, but were unable to express IFN-\u03b3. These same cells highly expressed IL-10, which inhibited TNF-\u03b1 and IL-6. Equally, THP-1 cells treated with Leish-EVs up-expressed miR-21-5p and miR-146a-5p. In conclusion, THP-1 cells treated with Leish-EVs highly expressed miR-21-5p and miR-146a-5p and caused the dysregulation of IL-10. Indirectly, these results suggest that high expression of these miRNAs species is caused by Leish-EVs. Consequently, this molecular via can contribute to immunosuppression causing enhanced immunopathology in infected hosts.<\/jats:p>","DOI":"10.3390\/microorganisms12020270","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:54:03Z","timestamp":1706518443000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Extracellular Vesicles from Leishmania (Leishmania) infantum Contribute in Stimulating Immune Response and Immunosuppression in Hosts with Visceral Leishmaniasis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-1212","authenticated-orcid":false,"given":"Francieli Marinho","family":"Carneiro","sequence":"first","affiliation":[{"name":"Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allecineia Bispo","family":"da Cruz","sequence":"additional","affiliation":[{"name":"Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Marques","family":"Maia","sequence":"additional","affiliation":[{"name":"Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-0787","authenticated-orcid":false,"given":"Noemi Nosomi","family":"Taniwaki","sequence":"additional","affiliation":[{"name":"N\u00facleo de Microscopia Eletr\u00f4nica, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid de Siqueira","family":"Pereira","sequence":"additional","affiliation":[{"name":"Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"},{"name":"N\u00facleo de Microscopia Eletr\u00f4nica, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gislene Mitsue","family":"Namiyama","sequence":"additional","affiliation":[{"name":"N\u00facleo de Microscopia Eletr\u00f4nica, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Gava","sequence":"additional","affiliation":[{"name":"Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto Mitsuyoshi","family":"Hiramoto","sequence":"additional","affiliation":[{"name":"Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Vicente","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Estrutural, Funda\u00e7\u00e3o Oswaldo Cruz, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9294-6597","authenticated-orcid":false,"given":"Victor","family":"Midlej","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Estrutural, Funda\u00e7\u00e3o Oswaldo Cruz, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8024-9612","authenticated-orcid":false,"given":"Rafael Meyer","family":"Mariante","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Estrutural, Funda\u00e7\u00e3o Oswaldo Cruz, Instituto Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3317-195X","authenticated-orcid":false,"given":"Vera Lucia","family":"Pereira-Chioccola","sequence":"additional","affiliation":[{"name":"Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, Sao Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2023, October 02). 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