{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:24:05Z","timestamp":1793384645593,"version":"4.5.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006675","name":"Instituto Nacional de Ci\u00eancia e Tecnologia de Doen\u00e7as Tropicais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006675","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Leishmaniasis is an infectious disease caused by protozoa of the genus <jats:italic>Leishmania<\/jats:italic>. There are still no vaccines, and therapeutic options are limited, indicating the constant need to understand the fine mechanisms of its pathophysiology. An approach that has been explored in leishmaniasis is the participation of microRNAs (miRNAs), a class of small non-coding RNAs that act, in most cases, to repress gene expression. miRNAs play a role in the complex and plastic interaction between the host and pathogens, either as part of the host\u2019s immune response to neutralize infection or as a molecular strategy employed by the pathogen to modulate host pathways to its own benefit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Monocyte-derived macrophages from healthy subjects were infected with isolates of three clinical forms of <jats:italic>L. braziliensis<\/jats:italic>: cutaneous (CL), mucosal (ML), and disseminated (DL) leishmaniasis. We compared the expression of miRNAs that take part in the TLR\/NFkB pathways. Correlations with parasite load as well as immune parameters were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>miRNAs -103a-3p, -21-3p, 125a-3p -155-5p, -146a-5p, -132- 5p, and -147a were differentially expressed in the metastatic ML and DL forms, and there was a direct correlation between miRNAs -103a-3p, -21-3p, -155-5p, -146a-5p, -132-5p, and -9-3p and parasite load with ML and DL isolates. We also found a correlation between the expression of miR-21-3p and miR-146a-5p with the antiapoptotic gene <jats:italic>BCL2<\/jats:italic> and the increase of viable cells, whereas miR-147a was indirectly correlated with CXCL-9 levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The expression of miRNAs is strongly correlated with the parasite load and the inflammatory response, suggesting the participation of these molecules in the pathogenesis of the different clinical forms of <jats:italic>L. braziliensis<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1280949","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T14:01:41Z","timestamp":1701957701000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["MicroRNAs regulating macrophages infected with Leishmania L. (V.) Braziliensis isolated from different clinical forms of American tegumentary leishmaniasis"],"prefix":"10.3389","volume":"14","author":[{"given":"Tain\u00e3","family":"Lago","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamile","family":"Lago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thyago","family":"Leal-Calvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar M.","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a Cristina","family":"Castellucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"B1","unstructured":"Leishmaniasis2023"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"Alvar","year":"2012","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/1993682104","article-title":"Phylogenetic taxonomy of new world leishmania","volume":"68","author":"Thomaz-Soccol","year":"1993","journal-title":"Ann Parasitol Hum Comp"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00059","article-title":"The influence of early neutrophil-Leishmania interactions on the host immune response to infection","volume":"2","author":"Ribeiro-Gomes","year":"2012","journal-title":"Front Cell Infect Microbiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.351","article-title":"Apoptotic cell clearance of Leishmania major-infected neutrophils by dendritic cells inhibits CD8+ T-cell priming in vitro by Mer tyrosine kinase-dependent signaling","volume":"6","author":"Ribeiro-Gomes","year":"2015","journal-title":"Cell Death Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00083","article-title":"The early interaction of Leishmania with macrophages and dendritic cells and its influence on the host immune response","volume":"2","author":"Liu","year":"2012","journal-title":"Front Cell Infect Microbiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/0169-4758(85)90057-2","article-title":"Clinical presentations of Leishmania Braziliensis","volume":"1","author":"Marsden","year":"1985","journal-title":"Parasitol Today"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(86)90243-9","article-title":"Mucosal leishmaniasis (\u201cespundia\u201d Escomel, 1911)","volume":"80","author":"Marsden","year":"1986","journal-title":"Trans R Soc Trop Med Hygiene"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/0001-706x(94)90103-1","article-title":"Clinical and immunopathological aspects of disseminated cutaneous leishmaniasis","volume":"56","author":"Carvalho","year":"1994","journal-title":"Acta Trop"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1590\/s0037-86822012000400001","article-title":"Parasite, vectors and reservoirs as determinants of tegumentary leishmaniasis","volume":"45","author":"Carvalho","year":"2012","journal-title":"Rev Soc Bras Med Trop"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1086\/345772","article-title":"Disseminated leishmaniasis: a new and emerging form of leishmaniasis observed in northeastern Brazil","volume":"186","author":"Turetz","year":"2002","journal-title":"J Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1590\/0037-8682-0463-2017","article-title":"Mucosal leishmaniasis: urgent need for more research","volume":"51","author":"Carvalho","year":"2018","journal-title":"Rev Soc Bras Med Trop"},{"key":"B13","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1590\/abd1806-4841.20198775","article-title":"Disseminated leishmaniasis: clinical, pathogenic, and therapeutic aspects","volume":"94","author":"MaChado","year":"2019","journal-title":"Bras Dermatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1034\/j.1600-065x.2000.917309.x","article-title":"Innate immune recognition: mechanisms and pathways","volume":"173","author":"Medzhitov","year":"2000","journal-title":"Immunol Ver"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/s0166-6851(03)00160-9","article-title":"Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2","volume":"130","author":"Becker","year":"2003","journal-title":"Mol Biochem Parasitol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324128","article-title":"MyD88 is essential for clearance of Leishmania major: possible role for lipophosphoglycan and Toll-like receptor 2 signaling","volume":"33","author":"de Veer","year":"2003","journal-title":"Eur J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00120","article-title":"Leishmania Braziliensis infection enhances toll-like receptors 2 and 4 expression and triggers TNF-\u03b1 and IL-10 production in human cutaneous leishmaniasis","volume":"9","author":"Polari","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.706510","article-title":"Blockade of TLR2 and TLR4 attenuates inflammatory response and parasite load in cutaneous leishmaniasis","volume":"12","author":"Carneiro","year":"2021","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(04)00045-5","article-title":"MicroRNAs: genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201400191","article-title":"Re-thinking miRNA-mRNA interactions: intertwining issues confound target discovery","volume":"37","author":"Cloonan","year":"2015","journal-title":"Bioessays"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002478","article-title":"MicroRNA expression profile in human macrophages in response to Leishmania major infection","volume":"7","author":"Lemaire","year":"2013","journal-title":"PloS Negl Trop Dis"},{"key":"B23","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1111\/pim.12156","article-title":"Characterization of microRNA expression profiles in Leishmania-infected human phagocytes","volume":"37","author":"Geraci","year":"2015","journal-title":"Parasite Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00640","article-title":"Integrated Analysis Reveals That miR-193b, miR-671, and TREM-1 Correlate With a Good Response to Treatment of Human Localized Cutaneous Leishmaniasis Caused by Leishmania Braziliensis","volume":"9","author":"Nunes","year":"2018","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02621","article-title":"The miRNA 361-3p, a regulator of GZMB and TNF is associated with therapeutic failure and longer time healing of cutaneous leishmaniasis caused by L","volume":"9","author":"Lago","year":"2018","journal-title":"(viannia) Braziliensis Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-12-75","article-title":"Macrophages participate in host protection and the disease pathology associated with Leishmania Braziliensis infection","volume":"12","author":"Giudice","year":"2012","journal-title":"BMC Infect Dis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02464","article-title":"Early suppression of macrophage gene expression by leishmania Braziliensis","volume":"9","author":"Sousa","year":"2018","journal-title":"Front Microbiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.687647","article-title":"miR-548d-3p alters parasite growth and inflammation in leishmania (Viannia) Braziliensis infection","volume":"11","author":"Souza","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c01502","article-title":"Systems Studies Uncover miR-146a as a Target in Leishmania major Infection Model","volume":"5","author":"Nimsarkar","year":"2020","journal-title":"ACS Omega"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.72","article-title":"Cutaneous leishmaniasis: immune responses in protection and pathogenesis","volume":"16","author":"Scott","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.740278","article-title":"The influence of infection by different leishmania (Viannia) Braziliensis isolates on the pathogenesis of disseminated leishmaniasis","volume":"11","author":"Oliveira","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00456","article-title":"Leishmania donovani-induced increase in macrophage bcl-2 favors parasite survival","volume":"7","author":"Pandey","year":"2016","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/j.ygeno.2006.06.002","article-title":"Anaplasma phagocytophilum causes global induction of antiapoptosis in human neutrophils","volume":"884","author":"Lee","year":"2006","journal-title":"Genomics"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2017.11.007","article-title":"CXCL9, CXCL10, CXCL11\/CXCR3 axis for immune activation - A target for novel cancer therapy","volume":"63","author":"Tokunaga","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.044","article-title":"Phosphorylation of the human microRNA-generating complex mediates MAPK\/Erk signaling","volume":"139","author":"Paroo","year":"2009","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65871","article-title":"MicroRNA-374a activates Wnt\/\u03b2-catenin signaling to promote breast cancer metastasis","volume":"123","author":"Cai","year":"2013","journal-title":"J Clin Invest"},{"key":"B37","doi-asserted-by":"publisher","first-page":"36","DOI":"10.2174\/1566524019666190820124827","article-title":"Candidate microRNAs as biomarkers in malaria infection: A systematic review","volume":"20","author":"Rangel","year":"2019","journal-title":"Curr Mol Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00165","article-title":"Role of microRNAs in schistosomes and schistosomiasis","volume":"4","author":"Zhu","year":"2014","journal-title":"Front Cell Infect Microbiol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1186\/s13071-019-3866-0","article-title":"The role of microRNAs in the pathogenesis, grading and treatment of hepatic fibrosis in schistosomiasis","volume":"12","author":"Chen","year":"2019","journal-title":"Parasit Vectors"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.05.019","article-title":"MicroRNAs miR-1, miR-133a, miR-133b, miR-208a and miR-208b are dysregulated in Chronic Chagas disease Cardiomyopathy","volume":"175","author":"Ferreira","year":"2014","journal-title":"Int J Cardiol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1590\/0074-02760150184","article-title":"Mir-190b negatively contributes to the Trypanosoma cruzi-infected cell survival by repressing PTEN protein expression","volume":"110","author":"Monteiro","year":"2015","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003828","article-title":"MicroRNA transcriptome profiling in heart of trypanosoma cruzi-infected mice: parasitological and cardiological outcomes","volume":"9","author":"Navarro","year":"2015","journal-title":"PloS Negl Trop Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1280949\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T14:01:44Z","timestamp":1701957704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1280949\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,7]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2023.1280949"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1280949","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,7]]},"article-number":"1280949"}}