{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T18:02:25Z","timestamp":1785261745791,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014510","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000}}],"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515011469"],"award-info":[{"award-number":["2024A1515011469"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"College Student Innovation and Entrepreneurship Training Project of SMU","award":["202212121045"],"award-info":[{"award-number":["202212121045"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32560848"],"award-info":[{"award-number":["32560848"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013055","name":"Guizhou Provincial Youth Science and Technology Talents Growth Project","doi-asserted-by":"publisher","award":["QN\u30142025\u3015163"],"award-info":[{"award-number":["QN\u30142025\u3015163"]}],"id":[{"id":"10.13039\/501100013055","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                    Brucellosis is a prevalent zoonotic disease that poses a serious threat to human health, particularly during pregnancy, where infection is strongly associated with spontaneous abortion. However, the mechanisms by which Brucella infection disrupts placental function remain poorly understood. Trophoblast cells are essential for placental development and represent primary targets of Brucella infection at the maternal\u2013fetal interface. In this study, we investigated the effects of Brucella outer membrane lipoprotein 16 (L16) on trophoblast cell fate using the human JEG-3 cell line. L16 markedly suppressed trophoblast cell proliferation and induced membrane damage, as evidenced by increased lactate dehydrogenase release. Unlike lipopolysaccharide stimulation, L16 triggered a lytic, non-apoptotic form of programmed cell death characterized by plasma membrane ballooning. Mechanistically, L16 activated caspase-3 and promoted cleavage of gasdermin E (GSDME) into its pore-forming N-terminal fragment, thereby executing GSDME-dependent pyroptosis. Silencing of caspase-3 abolished GSDME cleavage and significantly attenuated pyroptotic cell death, confirming the essential role of the caspase-3\/GSDME axis. Further analysis revealed that L16 reprogrammed inflammatory and survival signaling in trophoblast cells. L16 suppressed interleukin-6 (IL-6) trans-signaling by downregulating IL-6 receptor expression and up-regulating suppressor of cytokine signaling 3 (SOCS3), leading to inhibition of the JAK2\/STAT3 pathway. Concurrently, L16 inhibited PI3K\/AKT signaling and reduced phosphorylation of X-linked inhibitor of apoptosis protein (XIAP), thereby releasing inhibitory constraints on caspase-3 activation. Transcriptomic profiling supported coordinated repression of IL-6\/JAK\/STAT3 and PI3K\/AKT pathways following L16 exposure. Collectively, these findings identify L16 as a key\n                    <jats:italic>Brucella<\/jats:italic>\n                    virulence factor that induces trophoblast pyroptosis by rewiring IL-6 trans-signaling and survival pathways, providing new mechanistic insight into\n                    <jats:italic>Brucella<\/jats:italic>\n                    -associated pregnancy failure.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014510","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T17:32:52Z","timestamp":1784568772000},"page":"e0014510","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brucella outer membrane protein 16 induces trophoblast pyroptosis via rewiring IL-6 trans-signaling and caspase-3\/GSDME 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