{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:41:39Z","timestamp":1787316099708,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012543","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000}}],"reference-count":75,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81401683"],"award-info":[{"award-number":["81401683"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013254","name":"National College Students Innovation and Entrepreneurship Training Program","doi-asserted-by":"publisher","award":["202310304044Z"],"award-info":[{"award-number":["202310304044Z"]}],"id":[{"id":"10.13039\/501100013254","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016806","name":"Natural Science Foundation of Nantong Municipality","doi-asserted-by":"publisher","award":["JC2023100"],"award-info":[{"award-number":["JC2023100"]}],"id":[{"id":"10.13039\/100016806","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Decidual macrophages residing at the maternal-fetal interface have been recognized as pivotal factors for maintaining normal pregnancy; however, they are also key target cells of\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    (\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    ) in the pathology of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    -induced adverse pregnancy. Trem2, as a functional receptor on macrophage surface, recognizes and binds various kinds of pathogens. The role and underlying mechanism of Trem2 in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection remain elusive. In the present study, we found that\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection downregulated Trem2 expression and that Trem2\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice exhibited more severe adverse pregnancy outcomes than wildtype mice. We also demonstrated that\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection resulted in increased decidual macrophages, which were significantly reduced in the Trem2\n                    <jats:sup>-\/-<\/jats:sup>\n                    pregnant mouse model as compared to wildtype control animals. We further described the inhibited proliferation, migration, and invasion functions of trophoblast cell by\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    antigens through macrophages as an \"intermediate bridge\", while this inhibition can be rescued by Trem2 agonist HSP60. Concurrently, Trem2 deficiency in bone marrow-derived macrophages (BMDMs) heightened the inhibitory effect of\n                    <jats:italic>Tg<\/jats:italic>\n                    Ag on the migration and invasion of trophoblast cells, accompanied by higher pro-inflammatory factors (IL-1\u03b2, IL-6 and TNF-\u03b1) but a lower chemokine (CXCL1) in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    antigens-treated BMDMs. Furthermore, compelling evidence from animal models and\n                    <jats:italic>in vitro<\/jats:italic>\n                    cell experiments suggests that\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    inhibits the Trem2-Syk-PI3K signaling pathway, leading to impaired function of decidual macrophages. Therefore, our findings highlight Trem2 signaling as an essential pathway by which decidual macrophages respond to\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    infection, suggesting Trem2 as a crucial sensor of decidual macrophages and potential therapeutic target in the pathology of\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    -induced adverse pregnancy.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012543","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T13:32:14Z","timestamp":1725888734000},"page":"e1012543","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Trem2\/Syk\/PI3K axis contributes to the host protection against Toxoplasma gondii-induced adverse pregnancy outcomes via modulating decidual macrophages"],"prefix":"10.1371","volume":"20","author":[{"given":"Qing","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yining","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songyi","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoyuan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2992-6571","authenticated-orcid":true,"given":"Jinling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,9,9]]},"reference":[{"issue":"2","key":"ppat.1012543.ref001","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41579-021-00610-y","article-title":"Infections at the maternal\u2013fetal interface: an overview of pathogenesis and defence","volume":"20","author":"CJ Megli","year":"2021","journal-title":"Nature Reviews Microbiology"},{"key":"ppat.1012543.ref002","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3389\/fimmu.2020.621997","article-title":"Vaccines in Congenital Toxoplasmosis: Advances and Perspectives","volume":"11","author":"M Barros","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"ppat.1012543.ref003","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.3389\/fimmu.2018.01102","article-title":"Estradiol Attenuates the Severity of Primary Toxoplasma gondii Infection-Induced Adverse Pregnancy Outcomes Through the Regulation of Tregs in a Dose-Dependent Manner","volume":"9","author":"J Qiu","year":"2018","journal-title":"Frontiers in Immunology"},{"issue":"4","key":"ppat.1012543.ref004","doi-asserted-by":"crossref","first-page":"e1011329","DOI":"10.1371\/journal.ppat.1011329","article-title":"Tim-3 regulates the immunosuppressive function of decidual MDSCs via the Fyn-STAT3-C\/EBP\u03b2 pathway during Toxoplasma gondii infection","volume":"19","author":"LJ Knoll","year":"2023","journal-title":"PLOS Pathogens"},{"key":"ppat.1012543.ref005","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.placenta.2022.01.002","article-title":"Uterine damage induces placenta accreta and immune imbalance at the maternal-fetal interface in the mouse","volume":"119","author":"J Zhou","year":"2022","journal-title":"Placenta"},{"issue":"1","key":"ppat.1012543.ref006","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1186\/s13071-022-05560-9","article-title":"Effect of B7-H4 downregulation induced by Toxoplasma gondii infection on dysfunction of decidual macrophages contributes to adverse pregnancy outcomes","volume":"15","author":"L Cui","year":"2022","journal-title":"Parasites & Vectors"},{"issue":"1","key":"ppat.1012543.ref007","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s40261-018-0717-2","article-title":"Is It Necessary to Perform the Pharmacological Interventions for Intrahepatic Cholestasis of Pregnancy? 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