{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:13:55Z","timestamp":1782738835911,"version":"3.54.5"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Egyptian Ministry of Higher Education","award":["20000-04334000-12100-64099-EGYCU00037"],"award-info":[{"award-number":["20000-04334000-12100-64099-EGYCU00037"]}]},{"DOI":"10.13039\/100007921","name":"University of Pittsburgh","doi-asserted-by":"publisher","award":["start up funds"],"award-info":[{"award-number":["start up funds"]}],"id":[{"id":"10.13039\/100007921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012127","name":"Augusta University","doi-asserted-by":"publisher","award":["start up funds"],"award-info":[{"award-number":["start up funds"]}],"id":[{"id":"10.13039\/100012127","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content content-type=\"genus-species\">Leishmania donovani<\/jats:named-content>is a causative pathogen of potentially fatal visceral leishmaniasis (VL). Therapeutic agents are available; however, their use is limited because of high cost, serious side effects, and development of antimicrobial resistance. Protective immunity against VL depends on CD4<jats:sup>+<\/jats:sup>Th1 cell-mediated immunity. Studies have shown that progression of VL is due to exhaustion of T cells; however, the mechanism involved is not clearly understood. Here, we examined the role of PD1\/PDL-1 in the pathogenesis of VL by using a murine model of VL. Our data indicate that<jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>is able to elicit initial expansion of gamma interferon-producing CD4<jats:sup>+<\/jats:sup>Th1 and CD8<jats:sup>+<\/jats:sup>T cells at day 7 postinfection (p.i.); however, the frequency of those cells and inflammatory response decreased at day 21 p.i., despite persistence of parasites. Persistent infection-induced expansion of interleukin-10<jats:sup>+<\/jats:sup>FOXP3<jats:sup>+<\/jats:sup>Treg and CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells expressing PD1. Blocking of PDL-1 signaling<jats:italic>in vivo<\/jats:italic>resulted in restoration of protective type 1 responses by both CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells, which resulted in a significant decrease in the parasite burden. Mechanistically, PDL-1 blocking inhibited autophagy, a cellular degradation process hijacked by<jats:named-content content-type=\"genus-species\">Leishmania<\/jats:named-content>to acquire host cell nutrients for their survival. Inhibition of autophagy was marked by decreased lipidation of microtubule-associated protein 1 light chain 3, a marker of autophagosome formation, and P62 accumulation. Together, our findings show for the first time that anti-PDL-1 antibody is an effective therapeutic approach for restoration of effector arms of protective immunity against VL and subsequent parasite clearance.<\/jats:p>","DOI":"10.1128\/iai.00019-18","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T09:35:37Z","timestamp":1526895337000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":53,"title":["PDL-1 Blockade Prevents T Cell Exhaustion, Inhibits Autophagy, and Promotes Clearance of Leishmania donovani"],"prefix":"10.1128","volume":"86","author":[{"given":"Samar","family":"Habib","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical College of Georgia (MCG), Augusta University, Augusta, Georgia, USA"},{"name":"Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdeljabar","family":"El Andaloussi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled","family":"Elmasry","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia, USA"},{"name":"Department of Human Anatomy &amp; Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Handoussa","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar","family":"Azab","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliaa","family":"Elsawey","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman","family":"Al-Hendy","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahed","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2012.03.005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301810"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2007.07.004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.4049\/jimmunol.145.12.4311","article-title":"Serum resistance of metacyclic stage Leishmania major promastigotes is due to release of C5b-9","volume":"145","author":"Puentes SM","year":"1990","unstructured":"Puentes SM, Da Silva RP, Sacks DL, Hammer CH, Joiner KA. 1990. 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