{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T11:55:34Z","timestamp":1762170934932,"version":"build-2065373602"},"reference-count":71,"publisher":"Cambridge University Press (CUP)","issue":"8","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Parasites of the\n                    <jats:italic>Leishmania<\/jats:italic>\n                    species have been observed to infect macrophages and thereby modulate the host microbicidal responses, resulting in a wide spectrum of diseases. A comprehensive experimental mapping of the relationship between the double-stranded RNA protein kinase R (PKR) and NF-\u03baB pathways in the outcome of the infection was conducted in an effort to improve the understanding of the biology associated with the parasites\u2013host cell interaction. The results showed that in the absence of PKR and Type I Interferon (IFN) signalling,\n                    <jats:italic>L. major<\/jats:italic>\n                    infection was enhanced. The levels of PKR and gene promoter activation were evaluated. The results showed that infection did not induce PKR expression by inhibiting the phosphorylation of STAT1 and subsequent binding in the PKR promoter. However, infection induced PKR phosphorylation but did not prevent subsequent signalling through this pathway. To address the role of activation of these signalling, the induction of PKR-dependent gene expression was examined. Activation of the classical p65\/p50 dimer was found to be dependent on the PKR in the\n                    <jats:italic>L. major<\/jats:italic>\n                    infection, which was essential for the induction of iNOS, IFN\u03b2 and tumour necrosis factor expression. In addition, macrophages treated with nuclear factor-kB inhibitors were more susceptible to infection. Furthermore, translocation of the p65\/p50 to the promoters of these genes increased in a PKR-dependent manner. Collectively, these results suggest that macrophages retain their ability to induce important downstream effectors in PKR signalling. These effectors contribute to protection in pathogenesis, reducing parasite proliferation and regulating the inflammatory genes that, consequently, modulate the activation state of macrophages during infection.\n                  <\/jats:p>","DOI":"10.1017\/s0031182025100218","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T07:41:45Z","timestamp":1750059705000},"page":"834-847","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["The dsRNA-dependent kinase (PKR) inhibits the growth of\n                    <i>Leishmania major<\/i>\n                    via NF-\u03baB-mediated genes"],"prefix":"10.1017","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-257X","authenticated-orcid":false,"given":"\u00c1islan de Carvalho","family":"Vivarini","sequence":"first","affiliation":[{"name":"Fluminense Federal University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca Cristina Duarte","family":"Vivarini","sequence":"additional","affiliation":[{"name":"Fluminense Federal University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri Nunes","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Fluminense Federal University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Thiebaut","sequence":"additional","affiliation":[{"name":"Fluminense Federal University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelize Folly das","family":"Chagas","sequence":"additional","affiliation":[{"name":"Fluminense Federal 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The Author(s), 2025. Published by Cambridge University Press.","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}