{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T05:13:02Z","timestamp":1778562782076,"version":"3.51.4"},"reference-count":87,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Cutaneous leishmaniasis (CL) caused by\n                    <jats:italic>Leishmania braziliensis<\/jats:italic>\n                    results in chronic skin ulceration and remains challenging to treat. While human transcriptomic studies have identified pathways driving immunopathology, the early events of infection and the molecular transitions from lesion formation to healing are still poorly understood. Here, we performed a longitudinal transcriptomic analysis of skin lesions and draining lymph nodes (dLNs) in the BALB\/c ear dermal model infected with\n                    <jats:italic>L. braziliensis<\/jats:italic>\n                    , which recapitulates features of human CL. Using bulk RNA sequencing at 2, 6, and 48 hours and at 14, 35, and 77 days post-infection, we characterized differential gene expression, pathway enrichment, and gene co-expression networks. Ulcerated mouse lesions (Day 35) recapitulated 77% of the inflammatory pathways described in human CL, with many persisting at Day 77 despite \u201cclinical healing\u201d. Mice displayed additional upregulation of genes linked to macrophage polarization (\n                    <jats:italic>Il12a<\/jats:italic>\n                    ,\n                    <jats:italic>Il12b<\/jats:italic>\n                    ,\n                    <jats:italic>Il4<\/jats:italic>\n                    ), nitric oxide metabolism (\n                    <jats:italic>Arg1<\/jats:italic>\n                    ,\n                    <jats:italic>Nos2<\/jats:italic>\n                    ) and epidermal differentiation (e.g.,\n                    <jats:italic>Crnn<\/jats:italic>\n                    ,\n                    <jats:italic>Rptn<\/jats:italic>\n                    ,\n                    <jats:italic>Tchh<\/jats:italic>\n                    ,\n                    <jats:italic>Lce<\/jats:italic>\n                    members). Gene co-expression analysis revealed stage-specific gene modules (M) associated with early innate responses (M3), tissue damage (M1), epithelial-mesenchymal transition (M4), and skin barrier remodeling (M6). A long non-coding RNA-enriched module (M2) was selectively downregulated during the ulceration. Cross-species comparison of ulcerated lesions revealed 16 conserved microRNAs and 12 shared epigenetic regulators, including\n                    <jats:italic>Mir155<\/jats:italic>\n                    ,\n                    <jats:italic>Mir142<\/jats:italic>\n                    ,\n                    <jats:italic>Sp140<\/jats:italic>\n                    , and\n                    <jats:italic>Kdm6b<\/jats:italic>\n                    , with known roles in inflammation and tissue repair, representing promising host-directed therapeutic targets. Together, this study provides a comprehensive temporal framework of host responses to\n                    <jats:italic>L. braziliensis<\/jats:italic>\n                    and identifies actionable non-coding RNAs and epigenetic pathways with translational potential for CL therapy.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1752217","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:30:11Z","timestamp":1778560211000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal transcriptional dynamics in cutaneous leishmaniasis reveal novel targets for therapeutic interventions in a dermal mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Jessica","family":"Lobo-Silva","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Medicina e Sa\u00fade P\u00fablica de Precis\u00e3o (MeSP2), Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo 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Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regiane Degan","family":"F\u00e1varo","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias da Vida, Universidade do Estado da Bahia","place":["Salvador, Brazil"]},{"name":"Escola Bahiana de Medicina e Sa\u00fade P\u00fablica (EBMSP)","place":["Salvador, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce Karoline da","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Medicina e Sa\u00fade P\u00fablica de Precis\u00e3o (MeSP2), Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Salvador, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara Patr\u00edcia de Oliveira","family":"Santos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Medicina e Sa\u00fade P\u00fablica de Precis\u00e3o (MeSP2), Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo 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Tavares","family":"Machado","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Medicina e Sa\u00fade P\u00fablica de Precis\u00e3o (MeSP2), Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Salvador, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo Ivan Pereira","family":"Ramos","sequence":"additional","affiliation":[{"name":"Centro de Integra\u00e7\u00e3o de Dados e Conhecimento para Sa\u00fade, Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Salvador, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Khouri","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Medicina e Sa\u00fade P\u00fablica de Precis\u00e3o (MeSP2), Instituto Gon\u00e7alo Moniz, Funda\u00e7\u00e3o Oswaldo Cruz","place":["Salvador, Brazil"]},{"name":"Patologia, Diagn\u00f3stico por Imagem e Medicina Legal (DPML), Universidade Federal da Bahia 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