{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:58:17Z","timestamp":1790506697166,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009192","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000}}],"reference-count":110,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A-179400"],"award-info":[{"award-number":["31003A-179400"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["31003A-179439"],"award-info":[{"award-number":["31003A-179439"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background<\/jats:title><jats:p><jats:italic>Echinococcus multilocularis<\/jats:italic>causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying<jats:italic>E<\/jats:italic>.<jats:italic>multilocularis<\/jats:italic>infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during<jats:italic>E<\/jats:italic>.<jats:italic>multilocularis<\/jats:italic>infection in mice.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p><jats:italic>E<\/jats:italic>.<jats:italic>multilocularis-<\/jats:italic>and mock-infected C57BL\/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (\u03b1PD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post<jats:italic>i<\/jats:italic>.<jats:italic>p<\/jats:italic>. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p><jats:italic>E<\/jats:italic>.<jats:italic>multilocularis<\/jats:italic>infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2\u03b1 were not affected, and IRE1\u03b1 and ATF4 were downregulated. ABZ treatment in<jats:italic>E<\/jats:italic>.<jats:italic>multilocularis<\/jats:italic>infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1\u03b2, IL-6, tumor necrosis factor (TNF)-\u03b1 and interferon (IFN)-\u03b3 in the liver of infected mice. Similar to ABZ, \u03b1PD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1\u03b1 expression levels.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions and significance<\/jats:title><jats:p>AE caused chronic inflammation, UPR activation and ERS in mice. The<jats:italic>E<\/jats:italic>.<jats:italic>multilocularis<\/jats:italic>-induced inflammation and consecutive ERS was ameliorated by ABZ and \u03b1PD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor \u03b1PD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pntd.0009192","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T19:43:28Z","timestamp":1642189408000},"page":"e0009192","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis 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