{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T18:34:39Z","timestamp":1766428479673,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo State Research Foundation (FAPESP)","award":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"],"award-info":[{"award-number":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnologico (CNPq)","award":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"],"award-info":[{"award-number":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"]}]},{"name":"Laboratorio de Patologia de Mol\u00e9stias Infecciosas (LIM50)","award":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"],"award-info":[{"award-number":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"]}]},{"name":"UK: Brazil Joint Centre Partnership in Leishmaniasis","award":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"],"award-info":[{"award-number":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"]}]},{"name":"MRC New Investigator Research","award":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"],"award-info":[{"award-number":["2014\/50315-0","2020\/10430-6","2022\/16578-0","308817\/2021-4","HC-FMUSP","MR\/S019472\/1","MR\/T016019\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Leishmania (Leishmania) infantum chagasi infections range from asymptomatic (AS) to severe visceral leishmaniasis (VL). One of the manifestations is an atypical non-ulcerated cutaneous leishmaniasis (NUCL), which occurs in some locations of Central America with few cases of VL. We conducted a transcriptomic analysis of cell-mediated immunity (CMI) on blood samples from NUCL, AS, VL patients from Amapala, Honduras, and healthy controls. RNA-seq revealed a similar perturbation of gene expression in NUCL and AS. Eight gene signatures of CMI were found in NUCL involved in CD8+ T lymphocyte infiltration, reactive oxygen species generation, PD-1 receptor ligand, inflammasome assembly, chemotaxis, complement receptor and suppressor immune cell infiltration. NUCL was distinguished from VL by its up-regulation of differently expressed genes (DEGs) related to T lymphocyte exhaustion, adhesion and transmigration of leukocytes, and down-regulation of oxidative stress genes. In contrast, VL exhibited up-regulated DEGs involved in antigen cross-presentation, and similar to VL from Brazil, down-regulated DEGs involved in innate immunity. Corroborating the transcriptome findings, both the Leishmanin skin test, and the immunopathology of NUCL skin lesion defined NUCL as a proinflammatory condition, intermediate between the AS and VL clinical outcomes. That condition may be the underlying element for the benign nature of the NUCL.<\/jats:p>","DOI":"10.3390\/microorganisms13020413","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T10:36:58Z","timestamp":1739443018000},"page":"413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Insights into Cell-Mediated Immunity in Atypical Non-Ulcerated Cutaneous Leishmaniasis"],"prefix":"10.3390","volume":"13","author":[{"given":"Lu\u00eds F\u00e1bio S.","family":"Batista","sequence":"first","affiliation":[{"name":"Department of Pathology, Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6566-4869","authenticated-orcid":false,"given":"Carmen M.","family":"Sandoval Pacheco","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela V. Araujo","family":"Flores","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederico M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 N. A.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1387-7488","authenticated-orcid":false,"given":"Wilfredo H.","family":"Sosa-Ochoa","sequence":"additional","affiliation":[{"name":"Microbiology Research Institute, National Autonomous University of Honduras, Tegucigalpa 11101, Honduras"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3509-6121","authenticated-orcid":false,"given":"V\u00e2nia L. R.","family":"da Matta","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9909-9466","authenticated-orcid":false,"given":"Claudia M. C.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-792X","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Z\u00faniga","sequence":"additional","affiliation":[{"name":"Department of Health Surveillance, National Autonomous University of Honduras, Tegucigalpa 05005, Honduras"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos E. P.","family":"Corbett","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7320-0706","authenticated-orcid":false,"given":"Daniel C.","family":"Jeffares","sequence":"additional","affiliation":[{"name":"Department of Biology, York Biomedical Research Institute, University of York, York YO31 5DD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helder I.","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Hospital Israelita Albert Einstein, S\u00e3o Paulo 05620, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-6060","authenticated-orcid":false,"given":"Fernando T.","family":"Silveira","sequence":"additional","affiliation":[{"name":"Evandro Chagas Institute, Bel\u00e9m 66093-020, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-2440","authenticated-orcid":false,"given":"M\u00e1rcia D.","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0140-6736(91)90734-7","article-title":"Leishmania donovani chagasi: New clinical variant of cutaneous leishmaniasis in Honduras","volume":"337","author":"Ponce","year":"1991","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1006\/expr.1996.4133","article-title":"Leishmania chagasi: Genotypically similar parasites from Honduras cause both visceral and cutaneous leishmaniasis in humans","volume":"85","author":"Noyes","year":"1997","journal-title":"Exp. 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