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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,1,31]]},"abstract":"<jats:p>\n                    Toxoplasmosis is a neglected parasitic disease necessitating public health control. Host cell invasion by\n                    <jats:italic>Toxoplasma<\/jats:italic>\n                    occurs at different stages of the parasite\u2019s life cycle and is crucial for survival and establishment of infection. In tachyzoites, which are responsible for acute toxoplasmosis, invasion involves the formation of a molecular bridge between the parasite and host cell membranes, referred to as the moving junction (MJ). The MJ is shaped by the assembly of AMA1 and RON2, as part of a complex involving additional RONs. While this essential process is well characterized in tachyzoites, the invasion process remains unexplored in bradyzoites, which form cysts and are responsible for chronic toxoplasmosis and contribute to the dissemination of the parasite between hosts. Here, we show that bradyzoites invade host cells in an MJ-dependent fashion but differ in protein composition from the tachyzoite MJ, relying instead on the paralogs AMA2 and AMA4. Functional characterization of AMA4 reveals its key role for cysts burden during the onset of chronic infection, while being dispensable for the acute phase. Immunizations with AMA1 and AMA4, alone or in complex with their rhoptry neck respective partners RON2 and RON2\n                    <jats:sub>L1<\/jats:sub>\n                    , showed that the AMA1\u2013RON2 pair induces strong protection against acute and chronic infection, while the AMA4\u2013RON2\n                    <jats:sub>L1<\/jats:sub>\n                    complex targets more selectively the chronic form. Our study provides important insights into the molecular players of bradyzoite invasion and indicates that invasion of cyst-forming bradyzoites contributes to cyst burden. Furthermore, we validate AMA\u2013RON complexes as potential vaccine candidates to protect against toxoplasmosis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2219533120","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T13:36:38Z","timestamp":1674567398000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":25,"title":["Invasion of\n                    <i>Toxoplasma gondii<\/i>\n                    bradyzoites: Molecular dissection of the moving junction proteins and effective vaccination targets"],"prefix":"10.1073","volume":"120","author":[{"given":"Rania","family":"Najm","sequence":"first","affiliation":[{"name":"Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, 1107 2020 Beirut, Lebanon"},{"name":"LPHI, CNRS, INSERM, Universit\u00e9 de Montpellier, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8667-9250","authenticated-orcid":false,"given":"Margarida T. Grilo","family":"Ruivo","sequence":"additional","affiliation":[{"name":"LPHI, CNRS, INSERM, Universit\u00e9 de Montpellier, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Marcela","family":"Penarete-Vargas","sequence":"additional","affiliation":[{"name":"LPHI, CNRS, INSERM, Universit\u00e9 de Montpellier, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maguy","family":"Hamie","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, 1107 2020 Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mouveaux","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-8189","authenticated-orcid":false,"given":"Mathieu","family":"Gissot","sequence":"additional","affiliation":[{"name":"University of Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019-UMR 9017-CIIL- Center for Infection and Immunity of Lille, F-59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6835-9309","authenticated-orcid":false,"given":"Martin J.","family":"Boulanger","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8P 5C2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiba","family":"El Hajj","sequence":"additional","affiliation":[{"name":"Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, 1107 2020 Beirut, 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