{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:27:52Z","timestamp":1767205672022,"version":"build-2238731810"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Visceral leishmaniasis caused by\n                    <jats:italic>Leishmania (Leishmania) infantum<\/jats:italic>\n                    in Latin America progress with hepatosplenomegaly, pancytopenia, hypergammaglobulinemia, and weight loss and maybe lethal mainly in untreated cases. miRNAs are important regulators of immune and inflammatory gene expression, but their mechanisms of action and their relationship to pathogenesis in leishmaniasis are not well understood. In the present study, we sought to quantify changes in miRNAs associated with immune and inflammatory pathways using the\n                    <jats:italic>L. (L.) infantum<\/jats:italic>\n                    promastigote infected- human monocytic THP-1 cell model and plasma from patients with visceral leishmaniasis. We identified differentially expressed miRNAs in infected THP-1 cells compared with non-infected cells using qPCR arrays. These miRNAs were submitted to\n                    <jats:italic>in silico<\/jats:italic>\n                    analysis, revealing targets within functional pathways associated with TGF-\u03b2, chemokines, glucose metabolism, inflammation, apoptosis, and cell signaling. In parallel, we identified differentially expressed miRNAs in active visceral leishmaniasis patient plasma compared with endemic healthy controls.\n                    <jats:italic>In silico<\/jats:italic>\n                    analysis of these data indicated different predicted targets within the TGF-\u03b2, TLR4, IGF-I, chemokine, and HIF1\u03b1 pathways. Only a small number of miRNAs were commonly identified in these two datasets, notably with miR-548d-3p being up-regulated in both conditions. To evaluate the potential biological role of miR-548d-3p, we transiently transfected a miR-548d-3p inhibitor into\n                    <jats:italic>L. (L.) infantum<\/jats:italic>\n                    infected-THP-1 cells, finding that inhibition of miR-548d-3p enhanced parasite growth, likely mediated through reduced levels of MCP-1\/CCL2 and nitric oxide production. Further work will be required to determine how miR-548d-3p plays a role\n                    <jats:italic>in vivo<\/jats:italic>\n                    and whether it serves as a potential biomarker of progressive leishmaniasis.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2022.826039","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T02:37:47Z","timestamp":1644460667000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["miR-548d-3p\u00a0Is Up-Regulated in Human Visceral Leishmaniasis and Suppresses Parasite Growth in\u00a0Macrophages"],"prefix":"10.3389","volume":"12","author":[{"given":"Eduardo Milton","family":"Ramos-Sanchez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiza Campos","family":"Reis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina de Assis","family":"Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra M\u00e1rcia","family":"Muxel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamila Reis","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitris","family":"Lagos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9ria R\u00eago Alves","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Edileuza Felinto de","family":"Brito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul Martin","family":"Kaye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucile Maria","family":"Floeter-Winter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiro","family":"Goto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3390\/cells9010113","article-title":"MicroRNAs: Biological Regulators in Pathogen-Host Interactions","volume":"9","author":"Acuna","year":"2020","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e05005","DOI":"10.7554\/eLife.05005","article-title":"Predicting Effective microRNA Target Sites in Mammalian mRNAs","volume":"4","author":"Agarwal","year":"2015","journal-title":"Elife"},{"key":"B3","doi-asserted-by":"publisher","first-page":"W110","DOI":"10.1093\/nar\/gkw345","article-title":"miEAA: microRNA Enrichment Analysis and Annotation","volume":"44","author":"Backes","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1093\/infdis\/154.4.639","article-title":"A Prospective Study of Visceral Leishmaniasis in an Endemic Area of Brazil","volume":"154","author":"Badaro","year":"1986","journal-title":"J. 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