{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:23:14Z","timestamp":1787008994609,"version":"build-2736575974"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"12","funder":[{"DOI":"10.13039\/100000098","name":"National Institutes of Health Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Staphylococcus aureus (SA) bacterial pneumonia is a common cause of sepsis in intensive care units. Immune checkpoint inhibitors (CPIs) that target programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have been proposed for the treatment of sepsis. However, in our systematic review of sepsis preclinical models, none of the models examined CPIs in pneumonia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were inoculated intratracheally with vehicle control, low dose (LD)- or high dose (HD)-SA. Immune cell recruitment and checkpoint molecule expression were examined at 4, 24, and 48 hours after infection. Infected animals, treated with control or anti\u2013PD-L1 antibodies, were assessed for survival, bacterial burden, lung immunophenotypes, and mediator production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LD-SA and HD-SA produced lethality of 15% and 70%, respectively, by 168 hours. At 24 hours, LD-infected animals exhibited increased lung monocyte PD-L1 expression (P\u2005=\u2005.0002) but lower bacterial counts (P\u2005=\u2005.0002) compared with HD animals. By 48 hours, either infection induced lung neutrophil and macrophage PD-L1 expression (P\u2005&amp;lt;\u2005.0001). Anti\u2013PD-L1 treatment at the time of infection and at 24 hours following infection with low to high doses of SA reduced PD-L1 detection but did not affect survival or bacterial clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Anti\u2013PD-L1 therapy did not alter survival in this pneumonia model. Preclinical studies of additional common pathogens and septic foci are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiab274","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T07:20:29Z","timestamp":1621322429000},"page":"2073-2084","source":"Crossref","is-referenced-by-count":17,"title":["Anti\u2013PD-L1 Therapy Does Not Improve Survival in a Murine Model of Lethal\n                    <i>Staphylococcus aureus<\/i>\n                    Pneumonia"],"prefix":"10.1093","volume":"224","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-6494","authenticated-orcid":false,"given":"Colleen S","family":"Curran","sequence":"first","affiliation":[{"name":"Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay M","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Xizhong","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Sun","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Q","family":"Eichacker","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, Clinical Center, National 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