{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:30:16Z","timestamp":1781530216109,"version":"3.54.1"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2019R1C1C1004431"],"award-info":[{"award-number":["2019R1C1C1004431"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2017R1A5A2015385"],"award-info":[{"award-number":["2017R1A5A2015385"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["2022R1C1C1004346"],"award-info":[{"award-number":["2022R1C1C1004346"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sirtuin 1 (SIRT1) regulates cellular processes by deacetylating non-histone targets, including transcription factors and intracellular signalling mediators; thus, its abnormal activation is closely linked to the pathophysiology of several diseases. However, its function in Toxoplasma gondii infection is unclear. We found that SIRT1 contributes to autophagy activation via the AMP-activated protein kinase (AMPK) and PI3K\/AKT signalling pathways, promoting anti-Toxoplasma responses. Myeloid-specific Sirt1\u2212\/\u2212 mice exhibited an increased cyst burden in brain tissue compared to wild-type mice following infection with the avirulent ME49 strain. Consistently, the intracellular survival of T. gondii was markedly increased in Sirt1-deficient bone-marrow-derived macrophages (BMDMs). In contrast, the activation of SIRT1 by resveratrol resulted in not only the induction of autophagy but also a significantly increased anti-Toxoplasma effect. Notably, SIRT1 regulates the FoxO-autophagy axis in several human diseases. Importantly, the T. gondii-induced phosphorylation, acetylation, and cytosolic translocation of FoxO1 was enhanced in Sirt1-deficient BMDMs and the pharmacological inhibition of PI3K\/AKT signalling reduced the cytosolic translocation of FoxO1 in BMDMs infected with T. gondii. Further, the CaMKK2-dependent AMPK signalling pathway is responsible for the effect of SIRT1 on the FoxO3a-autophagy axis and for its anti-Toxoplasma activity. Collectively, our findings reveal a previously unappreciated role for SIRT1 in Toxoplasma infection.<\/jats:p>","DOI":"10.3390\/ijms232113578","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T10:53:06Z","timestamp":1667904786000},"page":"13578","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["SIRT1 Promotes Host Protective Immunity against Toxoplasma gondii by Controlling the FoxO-Autophagy Axis via the AMPK and PI3K\/AKT Signalling Pathways"],"prefix":"10.3390","volume":"23","author":[{"given":"Jina","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Min","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeonil","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwan-Doo","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Ho","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5795-8960","authenticated-orcid":false,"given":"Young-Ha","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Kyeong","family":"Jo","sequence":"additional","affiliation":[{"name":"Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3768-4285","authenticated-orcid":false,"given":"Byung-Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chonbuk National University Medical School, Jeonju 54896, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0630-9194","authenticated-orcid":false,"given":"Jae-Min","family":"Yuk","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Infection Control Convergence Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea"},{"name":"Department of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.pt.2010.01.009","article-title":"Toxoplasma gondii: Epidemiology, feline clinical aspects, and prevention","volume":"26","author":"Elmore","year":"2010","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/pim.12163","article-title":"Toxoplasma gondii dissemination: A parasite\u2019s journey through the infected host","volume":"37","author":"Harker","year":"2015","journal-title":"Parasite 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