{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:42:49Z","timestamp":1792086169012,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011347","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T00:00:00Z","timestamp":1682553600000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS095994"],"award-info":[{"award-number":["NS095994"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS095994-02S1"],"award-info":[{"award-number":["NS095994-02S1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F31AI147711"],"award-info":[{"award-number":["F31AI147711"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI147756"],"award-info":[{"award-number":["AI147756"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM121228"],"award-info":[{"award-number":["GM121228"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019002","name":"BIO5 Institute, University of Arizona","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> establishes a long-lived latent infection in the central nervous system (CNS) of its hosts. Reactivation in immunocompromised individuals can lead to life threatening disease. Latent infection is driven by the ability of the parasite to convert from the acute-stage tachyzoite to the latent-stage bradyzoite which resides in long-lived intracellular cysts. While much work has focused on the parasitic factors that drive cyst development, the host factors that influence encystment are not well defined. Here we show that a polymorphic secreted parasite kinase (ROP16), that phosphorylates host cell proteins, mediates efficient encystment of <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> in a stress-induced model of encystment and primary neuronal cell cultures (PNCs) in a strain-specific manner. Using short-hairpin RNA (shRNA) knockdowns in human foreskin fibroblasts (HFFs) and PNCs from transgenic mice, we determined that ROP16\u2019s cyst enhancing abilities are mediated, in part, by phosphorylation\u2014and therefore activation\u2014of the host cell transcription factor STAT6. To test the role of STAT6 <jats:italic>in vivo<\/jats:italic>, we infected wild-type (WT) and STAT6KO mice, finding that, compared to WT mice, STAT6KO mice have a decrease in CNS cyst burden but not overall parasite burden or dissemination to the CNS. Finally, we found a similar ROP16-dependent encystment defect in human pluripotent stem cell-derived neurons. Together, these findings identify a host cell factor (STAT6) that <jats:italic>T<\/jats:italic>. <jats:italic>gondii<\/jats:italic> manipulates in a strain-specific manner to generate a favorable encystment environment.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011347","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T17:37:50Z","timestamp":1681753070000},"page":"e1011347","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["ROP16-mediated activation of STAT6 enhances cyst development of type III Toxoplasma gondii in neurons"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7260-3159","authenticated-orcid":true,"given":"Joshua A.","family":"Kochanowsky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sambamurthy","family":"Chandrasekaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline R.","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin K.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8705-3233","authenticated-orcid":true,"given":"Anita A.","family":"Koshy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"key":"ppat.1011347.ref001","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1128\/CMR.11.2.267","article-title":"Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts","volume":"11","author":"JP Dubey","year":"1998","journal-title":"Clin Microbiol Rev"},{"key":"ppat.1011347.ref002","doi-asserted-by":"crossref","first-page":"D391","DOI":"10.2741\/Weiss","article-title":"The development and biology of bradyzoites of Toxoplasma gondii","volume":"5","author":"LM Weiss","year":"2000","journal-title":"Front Biosci"},{"key":"ppat.1011347.ref003","doi-asserted-by":"crossref","first-page":"S234","DOI":"10.1086\/344276","article-title":"Immunopathogenesis of Cerebral Toxoplasmosis","volume":"186","author":"Y. 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