{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T23:57:56Z","timestamp":1775519876513,"version":"3.50.1"},"reference-count":76,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/17261-5 and 2021\/07283-4"],"award-info":[{"award-number":["2018\/17261-5 and 2021\/07283-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/14894-0"],"award-info":[{"award-number":["2019\/14894-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Council for Scientific and Technological Development","award":["302165\/2018-5 and 140460\/2018-7"],"award-info":[{"award-number":["302165\/2018-5 and 140460\/2018-7"]}]},{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"crossref","award":["Finance Code 001"],"award-info":[{"award-number":["Finance Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Domestic dogs are the primary urban reservoirs of <jats:italic>Leishmania infantum<\/jats:italic>, the causative agent of visceral leishmaniasis. In Canine Leishmaniasis (CanL), modulation of the host\u2019s immune response may be associated with the expression of small non-coding RNAs called microRNA (miR). miR-194 expression increases in peripheral blood mononuclear cells (PBMCs) of dogs with leishmaniasis with a positive correlation with the parasite load and in silico analysis demonstrated that the TRAF6 gene is the target of miR-194 in PBMCs from diseased dogs. Here, we isolated PBMCs from 5 healthy dogs and 28 dogs with leishmaniasis, naturally infected with <jats:italic>L<\/jats:italic>. <jats:italic>infantum<\/jats:italic>. To confirm changes in miR-194 and TRAF6 expression, basal expression of miR-194 and gene expression of TRAF6 was measured using qPCR. PBMCs from healthy dogs and dogs with leishmaniasis were transfected with miR-194 scramble, mimic, and inhibitor and cultured at 37\u00b0 C, 5% CO<jats:sub>2<\/jats:sub> for 48 hours. The expression of possible targets was measured: iNOS, NO, T-bet, GATA3, and FoxP3 were measured using flow cytometry; the production of cytokines IL-1\u03b2, IL-4, IL-6, IL-10, TNF-\u03b1, IFN-\u03b3, and TGF-\u03b2 in cell culture supernatants was measured using capture enzyme-linked immunosorbent assays (ELISA). Parasite load was measured using cytometry and qPCR. Functional assays followed by miR-194 inhibitor and IL-1\u03b2 blockade and assessment of NO production were also performed. Basal miR-194 expression was increased in PBMC from dogs with Leishmaniasis and was negatively correlated with TRAF6 expression. The mimic of miR-194 promoted an increase in parasite load. There were no significant changes in T-bet, GATA3, or FoxP3 expression with miR-194 enhancement or inhibition. Inhibition of miR-194 increased IL-1\u03b2 and NO in PBMCs from diseased dogs, and blockade of IL-1\u03b2 following miR-194 inhibition decreased NO levels. These findings suggest that miR-194 is upregulated in PBMCs from dogs with leishmaniasis and increases parasite load, possibly decreasing NO production via IL-1\u03b2. These results increase our understanding of the mechanisms of evasion of the immune response by the parasite and the identification of possible therapeutic targets.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011789","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T19:00:26Z","timestamp":1705690826000},"page":"e0011789","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["MicroRNA-194 regulates parasitic load and IL-1\u03b2-dependent nitric oxide production in the peripheral blood mononuclear cells of dogs with leishmaniasis"],"prefix":"10.1371","volume":"18","author":[{"given":"Sidnei Ferro","family":"Costa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matheus Fujimura","family":"Soares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaqueline","family":"Poleto Bragato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilene Oliveira","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Torres","family":"Rebech","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9ssica Henrique","family":"de Freitas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0954-5045","authenticated-orcid":true,"given":"Val\u00e9ria Mar\u00e7al Felix","family":"de Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"pntd.0011789.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-308X(04)57001-X","article-title":"Canine leishmaniasis.","volume":"57","author":"J Alvar","year":"2004","journal-title":"Adv Parasitol"},{"key":"pntd.0011789.ref002","author":"World Health Organization","journal-title":"Leishmaniasis. 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