{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:54:05Z","timestamp":1788267245603,"version":"build-2803163510"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Shanghai Municipal Health Commission Project for Youth","award":["20214Y0206"],"award-info":[{"award-number":["20214Y0206"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272369"],"award-info":[{"award-number":["82272369"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019087","name":"Shanghai Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines","doi-asserted-by":"publisher","award":["GWVI-11.1-12"],"award-info":[{"award-number":["GWVI-11.1-12"]}],"id":[{"id":"10.13039\/501100019087","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><jats:italic>Toxoplasma gondii<\/jats:italic> infection induces anxiety in hosts during the chronic stage; however, its role in pre-anxiety-like behaviors during the acute stage remains poorly understood. This study investigates the role of Bradyzoite Formation Deficient 2 (BFD2), a transcription factor essential for tachyzoite-to-bradyzoite differentiation, in inflammation, apoptosis, and behavioral changes during acute <jats:italic>T. gondii<\/jats:italic> infection. Using CRISPR\/Cas9-mediated gene editing, we generated a <jats:italic>Bfd2<\/jats:italic> knockout strain (ME49\u2206<jats:italic>bfd2<\/jats:italic>) and observed reduced parasite proliferation and plaque formation, indicating BFD2\u2019s role in promoting <jats:italic>T. gondii<\/jats:italic> survival. RNA sequencing analysis of infected BV2 cells revealed that <jats:italic>Bfd2<\/jats:italic> deletion significantly downregulated inflammatory responses, with reduced expression of key inflammatory markers (interleukin 1 beta ((IL-1\u03b2), interferon gamma (IFN-\u03b3), and tumor necrosis factor alpha (TNF-\u03b1)) during acute infection. Next, we used western blotting, real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs) to verify that BFD2 improves the inflammation induced by acute stage <jats:italic>T. gondii<\/jats:italic> infection. <jats:italic>In vivo<\/jats:italic> studies confirmed that BFD2 exacerbates brain inflammation and neuronal apoptosis specifically during the acute stage, with no significant effects during the chronic stage. Behavior was assessed using the elevated plus maze test and open field test. Compared with the uninfected group and ME49\u2206<jats:italic>bfd2<\/jats:italic> group, the ME49 group mice showed an increased percentage of distance in the open arms and time in the open arm. The results showed that the total distance traveled, distance in the center, and time in the center were significantly decreased in the ME49 group, and the total distance traveled (mm) had no significant changes in the ME49\u2206<jats:italic>bfd2<\/jats:italic>. These demonstrated that BFD2 contributes to pre-anxiety-like behaviors in mice during acute stage <jats:italic>T. gondii<\/jats:italic> infection. These findings highlight BFD2 as a critical regulator of acute-stage inflammation, neuronal damage, and behavioral alterations, providing insights to develop targeted interventions against <jats:italic>T. gondii<\/jats:italic> infection.<\/jats:p>","DOI":"10.1371\/journal.pntd.0013428","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T17:47:18Z","timestamp":1757008038000},"page":"e0013428","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["BFD2 mediates inflammation, apoptosis, and pre-anxiety-like behaviors induced by acute Toxoplasma gondii 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