{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:22:48Z","timestamp":1790518968017,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010544","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000}}],"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204797\/Z\/16\/Z"],"award-info":[{"award-number":["204797\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206508\/Z\/17\/Z"],"award-info":[{"award-number":["206508\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Visceral leishmaniasis (VL) is a neglected tropical disease that causes substantial morbidity and mortality and is a growing health problem in Ethiopia, where this study took place. Most individuals infected with\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    parasites will stay asymptomatic, but some develop VL that, if left untreated, is almost always fatal. This stage of the disease is associated with a profound immunosuppression, characterised by impaired production of Interferon\u03b3 (IFN\u03b3), a cytokine that plays a key role in the control of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    parasites, and high expression levels of an inhibitory receptor, programmed cell death 1 (PD1) on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Here, we tested the contribution of the interaction between the immune checkpoint PD1 and its ligand PDL-1 on the impaired production of IFN\u03b3 in VL patients. Our results show that in the blood of VL patients, not only CD4\n                    <jats:sup>+<\/jats:sup>\n                    , but also CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells express high levels of PD1 at the time of VL diagnosis. Next, we identified PDL-1 expression on different monocyte subsets and neutrophils and show that PDL-1 levels were significantly increased in VL patients. PD1\/PDL-1 inhibition resulted in significantly increased production of IFN\u03b3, suggesting that therapy using immune checkpoint inhibitors might improve disease control in these patients.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0010544","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T14:04:01Z","timestamp":1656079441000},"page":"e0010544","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impaired in vitro Interferon-\u03b3 production in patients with visceral leishmaniasis is improved by inhibition of PD1\/PDL-1 ligation"],"prefix":"10.1371","volume":"16","author":[{"given":"Yegnasew","family":"Takele","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emebet","family":"Adem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne Ursula","family":"Franssen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Womersley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrsini","family":"Kaforou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Levin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James Anthony","family":"Cotton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1670-8332","authenticated-orcid":true,"given":"Pascale","family":"Kropf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"pntd.0010544.ref001","first-page":"285","article-title":"Leishmaniasis in high-burden countries: an epidemiological update based on data reported in 2014","volume":"91","author":"WHO","year":"2016","journal-title":"Wkly Epidemiol Rec"},{"key":"pntd.0010544.ref002","first-page":"265","article-title":"Jaina LGaS. 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