{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:25:07Z","timestamp":1790871907008,"version":"4.1.0"},"reference-count":76,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T00:00:00Z","timestamp":1677801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation (FAPESP)","doi-asserted-by":"publisher","award":["2014\/50315-0"],"award-info":[{"award-number":["2014\/50315-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation (FAPESP)","doi-asserted-by":"publisher","award":["2020\/02626-8"],"award-info":[{"award-number":["2020\/02626-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nucleus of Tropical Medicine of Federal University of Par\u00e1 State, Brazil","award":["2014\/50315-0"],"award-info":[{"award-number":["2014\/50315-0"]}]},{"name":"Nucleus of Tropical Medicine of Federal University of Par\u00e1 State, Brazil","award":["2020\/02626-8"],"award-info":[{"award-number":["2020\/02626-8"]}]},{"name":"Secretary of Health and Environment Surveillance of Ministry of Health, Brazil","award":["2014\/50315-0"],"award-info":[{"award-number":["2014\/50315-0"]}]},{"name":"Secretary of Health and Environment Surveillance of Ministry of Health, Brazil","award":["2020\/02626-8"],"award-info":[{"award-number":["2020\/02626-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Individuals infected with Leishmania (L.) chagasi may present different asymptomatic and symptomatic stages of infection, which vary in the clinical\u2013immunological profiles that can be classified as asymptomatic infection (AI), subclinical resistant infection (SRI), indeterminate initial infection (III), subclinical oligosymptomatic infection (SOI), and symptomatic infection (SI) (=American visceral leishmaniasis, AVL). However, little is known about the molecular differences between individuals having each profile. Here, we performed whole-blood transcriptomic analyses of 56 infected individuals from Par\u00e1 State (Brazilian Amazon), covering all five profiles. We then identified the gene signatures of each profile by comparing their transcriptome with those of 11 healthy individuals from the same area. Symptomatic individuals with SI (=AVL) and SOI profiles showed higher transcriptome perturbation when compared to those asymptomatic III, AI and SRI profiles, suggesting that disease severity may be associated with greater transcriptomic changes. Although the expression of many genes was altered on each profile, very few genes were shared among the profiles. This indicated that each profile has a unique gene signature. The innate immune system pathway was strongly activated only in asymptomatic AI and SRI profiles, suggesting the control of infection. In turn, pathways such as MHC Class II antigen presentation and NF-kB activation in B cells seemed to be specifically induced in symptomatic SI (=AVL) and SOI profiles. Moreover, cellular response to starvation was down-regulated in those symptomatic profiles. Overall, this study revealed five distinct transcriptional patterns associated to the clinical\u2013immunological (symptomatic and asymptomatic) profiles of human L. (L.) chagasi-infection in the Brazilian Amazon.<\/jats:p>","DOI":"10.3390\/microorganisms11030653","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T03:32:52Z","timestamp":1677814372000},"page":"653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gene Signatures of Symptomatic and Asymptomatic Clinical-Immunological Profiles of Human Infection by Leishmania (L.) chagasi in Amazonian Brazil"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3509-6121","authenticated-orcid":false,"given":"Vania Lucia R.","family":"da Matta","sequence":"first","affiliation":[{"name":"Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5264-8368","authenticated-orcid":false,"given":"Andr\u00e9 N.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9909-9466","authenticated-orcid":false,"given":"Cl\u00e1udia Maria C.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islam H.","family":"Chouman","sequence":"additional","affiliation":[{"name":"Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederico M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marliane B.","family":"Campos","sequence":"additional","affiliation":[{"name":"Parasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-2835","authenticated-orcid":false,"given":"Luciana V.","family":"Lima","sequence":"additional","affiliation":[{"name":"Parasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0229-4861","authenticated-orcid":false,"given":"Thiago","family":"Vasconcelos dos Santos","sequence":"additional","affiliation":[{"name":"Parasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Karla","family":"Ramos","sequence":"additional","affiliation":[{"name":"Parasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3489-5979","authenticated-orcid":false,"given":"Rodrigo R.","family":"Furtado","sequence":"additional","affiliation":[{"name":"Parasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-2440","authenticated-orcid":false,"given":"Marcia D.","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Eduardo P.","family":"Corbett","sequence":"additional","affiliation":[{"name":"Laboratorio de Patologia de Molestias Infecciosas (LIM-50), Departamento de Patologia, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 01246 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helder I.","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Ciencias Farmaceuticas, Universidade de Sao Paulo, Sao Paulo 05508-220, Brazil"},{"name":"Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-6060","authenticated-orcid":false,"given":"Fernando T.","family":"Silveira","sequence":"additional","affiliation":[{"name":"Parasitology Department, Evandro Chagas Institute, Health Surveillance Secretary, Ministry of Health, Ananindeua 67030-000, Brazil"},{"name":"Tropical Medicine Nucleus, Par\u00e1 Federal University, Bel\u00e9m 67030-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,3]]},"reference":[{"key":"ref_1","first-page":"143","article-title":"Leishmania chagasi Cunha & Chagas, 1937: Indigenous or introduced? 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