{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:19:43Z","timestamp":1790702383523,"version":"4.1.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T00:00:00Z","timestamp":1512518400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T00:00:00Z","timestamp":1512518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Leishmania<\/jats:italic> parasites utilize adaptive evasion mechanisms in infected macrophages to overcome host defenses and proliferate. We report here that the PERK\/eIF2\u03b1\/ATF4 signaling branch of the integrated endoplasmic reticulum stress response (IERSR) is activated by <jats:italic>Leishmania<\/jats:italic> and this pathway is important for <jats:italic>Leishmania amazonensis<\/jats:italic> infection. Knocking down PERK or ATF4 expression or inhibiting PERK kinase activity diminished <jats:italic>L<\/jats:italic>. <jats:italic>amazonensis<\/jats:italic> infection. Knocking down ATF4 decreased NRF2 expression and its\u00a0nuclear translocation, reduced HO-1 expression and increased nitric oxide production. Meanwhile, the\u00a0increased expression of ATF4 and HO-1 mRNAs were observed\u00a0in lesions derived from\u00a0patients infected with the prevalent related species <jats:italic>L<\/jats:italic>.<jats:italic>(V<\/jats:italic>.<jats:italic>) braziliensis<\/jats:italic>. Our data demonstrates that <jats:italic>Leishmania<\/jats:italic> parasites activate the PERK\/eIF2\u03b1\/ATF-4 pathway in cultured macrophages and infected human tissue and that this pathway is important for parasite survival\u00a0and progression of the infection.<\/jats:p>","DOI":"10.1038\/s41598-017-17252-x","type":"journal-article","created":{"date-parts":[[2017,11,30]],"date-time":"2017-11-30T12:11:04Z","timestamp":1512043864000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Emerging Role for the PERK\/eIF2\u03b1\/ATF4 in Human Cutaneous Leishmaniasis"],"prefix":"10.1038","volume":"7","author":[{"given":"Karina Luiza","family":"Dias-Teixeira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa C.","family":"Calegari-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge M.","family":"Medina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1islan C.","family":"Vivarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1tila","family":"Cavalcanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataly","family":"Teteo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alynne Karen M.","family":"Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5060-4334","authenticated-orcid":false,"given":"Fernando","family":"Real","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3069-6884","authenticated-orcid":false,"given":"Ciro M.","family":"Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Meirelles Santos","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Fasel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o S.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertal H.","family":"Aktas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulisses G.","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,6]]},"reference":[{"key":"17252_CR1","unstructured":"World Health Organization (WHO). 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