{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:30:56Z","timestamp":1786113056813,"version":"build-2736575974"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI181315"],"award-info":[{"award-number":["AI181315"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["GAANN P200A210024"],"award-info":[{"award-number":["GAANN P200A210024"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The TREM2 receptor is a well-known rheostat for inflammation and immunity, but its role in host defense against parasitic infection is only just emerging. We investigated the function of TREM2 during acute\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    infection by comparing TREM2-deficient and C57BL\/6 wild-type (WT) mice during intraperitoneal infection with type II (\n                    <jats:italic>Prugniaud<\/jats:italic>\n                    strain)\n                    <jats:italic>T. gondii<\/jats:italic>\n                    . Infected TREM2 knockout (KO) mice had significantly increased mortality and elevated parasite burden during acute infection, as well as increased liver pathology and higher levels of inflammatory cytokines IL-1\u03b1, IL-6, and IL-17A by 7 days post-infection (dpi). Notably, we observed an early expansion and dissemination of\n                    <jats:italic>T. gondii<\/jats:italic>\n                    in infected macrophages in the omentum in TREM2 KO compared to WT mice, and this phenotype was specific to TREM2 deficiency on radiation-sensitive cells, based on bone marrow chimera experiments.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , TREM2 KO macrophages were more permissive to\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infection and exhibited reduced LAMP1 upregulation and impaired phagocytotic clearance of\n                    <jats:italic>T. gondii<\/jats:italic>\n                    compared to WT macrophages. TREM2 deficiency has been previously associated with elevated ERK signaling and defective lysosomal activity, and we found that treatment of TREM2 KO macrophages with the ERK inhibitor SCH772984 rescued LAMP1 expression and improved macrophage control of the parasites. Finally, RNA sequencing of myeloid cells isolated from the peritoneal cavity of infected mice at 3 dpi revealed increased transcripts associated with inflammation and decreased transcripts associated with cellular migration in the TREM2 KO compared to WT mice. These findings demonstrate a critical role for TREM2 in the early antimicrobial immune response to\n                    <jats:italic>T. gondii<\/jats:italic>\n                    infection by limiting parasite expansion, dissemination, and pathological inflammation in the infected host.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014462","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:32:49Z","timestamp":1785951169000},"page":"e1014462","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["TREM2 plays a critical role in innate immune defense against acute Toxoplasma gondii infection by promoting macrophage antimicrobial activities"],"prefix":"10.1371","volume":"22","author":[{"given":"Hannah Z.","family":"Debray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dillon","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6272-3314","authenticated-orcid":true,"given":"L. Angel","family":"Ayala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toan","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hun","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dequina A.","family":"Nicholas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Inlay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Drayman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3366-6840","authenticated-orcid":true,"given":"Melissa 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Gigley","year":"2009","journal-title":"J Immunol"},{"issue":"3","key":"ppat.1014462.ref006","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.clp.2005.04.011","article-title":"Diagnosis and management of toxoplasmosis","volume":"32","author":"JG Montoya","year":"2005","journal-title":"Clin Perinatol"},{"issue":"1","key":"ppat.1014462.ref007","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1600-065X.2010.00992.x","article-title":"Immunology of Toxoplasma gondii","volume":"240","author":"M Munoz","year":"2011","journal-title":"Immunol Rev"},{"issue":"4851","key":"ppat.1014462.ref008","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1126\/science.3128869","article-title":"Interferon-gamma: the major mediator of resistance against Toxoplasma gondii","volume":"240","author":"Y 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Ustun","year":"2004","journal-title":"World J Gastroenterol"},{"issue":"11","key":"ppat.1014462.ref031","doi-asserted-by":"crossref","DOI":"10.1016\/j.immuni.2021.10.007","article-title":"Resident macrophage-dependent immune cell scaffolds drive anti-bacterial defense in the peritoneal cavity","volume":"54","author":"A Vega-P\u00e9rez","year":"2021","journal-title":"Immunity"},{"issue":"75","key":"ppat.1014462.ref032","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abq7432","article-title":"cDC1 coordinate innate and adaptive responses in the omentum required for T cell priming and memory","volume":"7","author":"DA Christian","year":"2022","journal-title":"Sci Immunol"},{"issue":"1","key":"ppat.1014462.ref033","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1186\/s12974-022-02629-1","article-title":"Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination","volume":"19","author":"M 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