{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T16:47:32Z","timestamp":1758818852087,"version":"3.41.2"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82272364, 81971954"],"award-info":[{"award-number":["82272364, 81971954"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81802024"],"award-info":[{"award-number":["81802024"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,12,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Toxoplasma gondii<\/jats:italic>\n            is an important intracellular protozoan, which needs to exploit host nutrition for successful parasitism. We previously reported that Casitas B-lineage lymphoma-b (Cbl-b) was screened as a host dependency factor of\n            <jats:italic>T. gondii<\/jats:italic>\n            by using lentiviral CRISPR-Cas9-single guide RNA (sgRNA) libraries. Furthermore, the detailed mechanism of Cbl-b being required by\n            <jats:italic>T. gondii<\/jats:italic>\n            infection was explored in this study. The proliferation of\n            <jats:italic>T. gondii<\/jats:italic>\n            was found to be significantly inhibited in Cbl-b knockdown cell lines, and the Cbl-b expression level increased with prolonged\n            <jats:italic>T. gondii<\/jats:italic>\n            infection, while the MyD88 level was significantly decreased in the\n            <jats:italic>T. gondii<\/jats:italic>\n            infection group. Toll-like receptor (TLR)\/MyD88 is a conserved innate cellular immune signaling pathway against pathogens infection. Cbl-b was found to interact with MyD88 and mediate MyD88 ubiquitination in the fluorescence resonance energy transfer and co-immunoprecipitation experiments. A Cbl-b knockout (KO) C57BL\/6J lineage was then constructed and, together with the wild-type (WT) mice, was infected with the same amount of\n            <jats:italic>T. gondii<\/jats:italic>\n            tachyzoites of ME49 strain. At 13 days post infection, all the mice in the WT group died, while 80% of the mice in the Cbl-b KO group still survived, even to the end of the experiment. The parasitic burden in the liver, lung, and brain of the Cbl-b KO mice was significantly lower than that of the WT mice (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). In Cbl-b KO infected mice, the percentage of B cells was higher, whereas that of macrophages was lower, and the interferon-\u03b3 and interleukin-6 levels in the serum were higher than that in the WT infected mice; the difference was significant (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). Furthermore, when host cells were infected by\n            <jats:italic>T. gondii<\/jats:italic>\n            , host\u2019s Cbl-b was found to interact with MyD88 to ubiquitinate MyD88 for ribosome-dependent degradation. Therefore, the host\u2019s innate immunity against\n            <jats:italic>T. gondii<\/jats:italic>\n            through the TLR\/MyD88 pathway was negatively regulated by Cbl-b.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              This is the first report that a human E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (Cbl-b), functions as a host dependency factor for the intracellular protozoan\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              and the mechanism for how\n              <jats:italic>T. gondii<\/jats:italic>\n              infection inhibits the TLR\/MyD88 innate immunity pathway through MyD88 degradation mediated by Cbl-b. This finding is an impactful contribution for understanding the host cell immunity against\n              <jats:italic>T. gondii<\/jats:italic>\n              infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00074-23","type":"journal-article","created":{"date-parts":[[2023,11,1]],"date-time":"2023-11-01T13:29:16Z","timestamp":1698845356000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Cbl-b negatively regulates TLR\/MyD88-mediated anti-\n            <i>Toxoplasma gondii<\/i>\n            immunity"],"prefix":"10.1128","volume":"11","author":[{"given":"Haixia","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Medicine, School of Public Health, Southern Medical University , Guangzhou, Guangdong, China"},{"name":"Department of Pathogen Biology, School of Basic Medicine, Guangzhou Medical University , Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuizhen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Medicine, School of Public Health, Southern Medical University , Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liying","family":"Mai","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Medicine, School of Public Health, Southern Medical University , Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Medicine, School of Public Health, Southern Medical University , Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weihao","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Medicine, School of Public Health, Southern Medical University , Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9345-8218","authenticated-orcid":false,"given":"Hongjuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Medicine, School of Public Health, Southern Medical University , Guangzhou, Guangdong, 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