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The C57BL\/6J mouse strain is regarded as an ideal model organism for studying T. gondii due to its susceptibility to T. gondii infection and its other advantages over other laboratory animals. However, systematic studies on the response dynamics of the susceptible C57BL\/6J mice after oral infection with T. gondii cysts are lacking. To address this research gap, we investigated the spatiotemporal dynamics of infection, colonization, and antibody fluctuations in susceptible C57BL\/6J mice orally infected with Type II T. gondii ME49 strain cysts. Mice were orally challenged with T. gondii cysts to examine the infection dynamics. Daily monitoring was conducted for 60 days post-infection (dpi) to assess animals\u2019 clinical signs and survival rates. The parasite burden in various organs was quantified using qPCR targeting the T. gondii B1 gene. The serum antibody responses were evaluated using ELISA. The cyst burden in the mouse brain was assessed via histology and immunofluorescence. T. gondii infection induced clinical symptoms in the mice, including fever and weight loss. T. gondii rapidly invaded the mice\u2019s small intestine, spleen, lungs, liver, and heart via the bloodstream within 1\u20135 dpi. T. gondii had breached the blood\u2013brain barrier and colonized the brain by 7 dpi. The levels of Toxoplasma-specific IgG antibodies increased and stabilized for two months (until the experiment ended). Systemic parasite dissemination occurred rapidly, infiltrating most tissues and organs, leading to pronounced enteritis and multi-organ damage due to inflammation. The tachyzoites differentiated into bradyzoites when T. gondii infection progressed from the acute to the chronic phase in mice, forming tissue cysts in organs, including the muscles and brain. As a result, the predilection site of T. gondii in mice is the brain, which is where the cysts persisted for the host\u2019s lifetime and continuously induced meningitis. These findings provide valuable insights into the spatiotemporal diffusion, colonization, predilection sites, temporal antibody dynamics, pathogen detection methodologies, and histopathological changes in C57BL\/6J mice following oral infection with T. gondii cysts. These insights are important for elucidating T. gondii\u2019s pathogenesis and host\u2013T. gondii interaction.<\/jats:p>","DOI":"10.3390\/vetsci12030212","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T03:22:44Z","timestamp":1740972164000},"page":"212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Spatiotemporal Diffusion, Colonization, and Antibody Responses in Susceptible C57BL\/6J Mice Orally Infected with Toxoplasma gondii Cysts"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7848-0152","authenticated-orcid":false,"given":"Zhao","family":"Li","sequence":"first","affiliation":[{"name":"Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China"},{"name":"Animal Research and Resource Center, School of Life Sciences, Yunnan University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7514-3994","authenticated-orcid":false,"given":"Qi-Shuai","family":"Liu","sequence":"additional","affiliation":[{"name":"Animal Research and Resource Center, School of Life Sciences, Yunnan University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3729-735X","authenticated-orcid":false,"given":"Jun-Jie","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Ecology and Environmental Science, Yunnan University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-Qin","family":"Deng","sequence":"additional","affiliation":[{"name":"Animal Research and Resource Center, School of Life Sciences, Yunnan University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[{"name":"Animal Research and Resource Center, School of Life Sciences, Yunnan University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7621-4628","authenticated-orcid":false,"given":"Wen-Bin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2530-4628","authenticated-orcid":false,"given":"Xing-Quan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China"},{"name":"The Yunnan Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9613-3734","authenticated-orcid":false,"given":"Feng-Cai","family":"Zou","sequence":"additional","affiliation":[{"name":"The Yunnan Key Laboratory of Veterinary Etiological Biology, College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dubey, J.P. 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