{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T04:45:36Z","timestamp":1776573936918,"version":"3.51.2"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2023A1515011820"],"award-info":[{"award-number":["2023A1515011820"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Laboratory of Viral Pathogenesis & Infection Prevention and Control of the Ministry of Education","award":["2024VPPC-S06"],"award-info":[{"award-number":["2024VPPC-S06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: The NF-\u03baB signaling pathway plays a critical role in innate immune defense against infections. However, many pathogens secrete toxins or effectors into host cells to manipulate cellular functions for their survival and proliferation. Toxoplasma gondii is known to establish chronic infections by employing sophisticated immune evasion strategies. Dense granule (GRA) proteins are essential for the survival and pathogenesis of T. gondii. Methods: In this study, plasmid transfection, cell culture, luciferase reporter assay, quantitative PCR, and western blot were employed to identify T. gondii GRA proteins that regulate the NF-\u03baB pathway. Results: We demonstrate that GRA12, a specific GRA protein, significantly inhibits NF-\u03baB promoter activity and the transcriptional expression of key cytokines, including IL-6, IL-12, TNF-\u03b1, and IFN-\u03b2. Western blot analysis further revealed that GRA12 suppresses the activation of the IKK complex and p65. Moreover, GRA12 prevents the nuclear translocation of p65. Conclusions: Our findings demonstrate that GRA12 is involved in immune evasion by inhibiting the NF-\u03baB pathway, thereby facilitating T. gondii dissemination and infection.<\/jats:p>","DOI":"10.3390\/genes17040476","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T14:24:51Z","timestamp":1776435891000},"page":"476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxoplasma gondii GRA12 Inhibits the NF-\u039aB Signaling Pathway by Targeting P65 and the IKK Complex"],"prefix":"10.3390","volume":"17","author":[{"given":"Meiling","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China"},{"name":"Jiangmen Center for Disease Control and Prevention, Jiangmen 529000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0752-7917","authenticated-orcid":false,"given":"Zhizhuo","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China"},{"name":"Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9965-6706","authenticated-orcid":false,"given":"Boren","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuying","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7333-4181","authenticated-orcid":false,"given":"Chunxia","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, School of Medicine, Jinan University, Guangzhou 510632, China"},{"name":"Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-515X","authenticated-orcid":false,"given":"Guang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, China"},{"name":"Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 510632, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rohaim, M.A., Santhakumar, D., Naggar, R.F.E., Iqbal, M., Hussein, H.A., and Munir, M. 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