{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:23:14Z","timestamp":1792718594518,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011502","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI136538"],"award-info":[{"award-number":["R01AI136538"]}],"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":["R01AI121090"],"award-info":[{"award-number":["R01AI121090"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI007285"],"award-info":[{"award-number":["AI007285"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Host resistance to a common protozoan parasite\n                    <jats:italic>Toxoplasma gondii<\/jats:italic>\n                    relies on a coordinated immune response involving multiple cell types, including macrophages. Embryonically seeded tissue-resident macrophages (TRMs) play a critical role in maintaining tissue homeostasis, but their role in parasite clearance is poorly understood. In this study, we uncovered a crucial aspect of host defense against\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    mediated by TRMs. Through the use of neutralizing antibodies and conditional IFN-\u03b3 receptor-deficient mice, we demonstrated that IFN-\u03b3 directly mediated the elimination of TRMs. Mechanistically, IFN-\u03b3 stimulation\n                    <jats:italic>in vivo<\/jats:italic>\n                    rendered macrophages unresponsive to macrophage colony-stimulating factor (M-CSF) and inactivated mTOR signaling by causing the shedding of CD115 (CSFR1), the receptor for M-CSF. Further experiments revealed the essential role of macrophage IFN-\u03b3 responsiveness in host resistance to\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>gondii<\/jats:italic>\n                    . The elimination of peritoneal TRMs emerged as an additional host defense mechanism aimed at limiting the parasite\u2019s reservoir. The identified mechanism, involving IFN-\u03b3-induced suppression of CD115-dependent mTOR signaling in macrophages, provides insights into the adaptation of macrophage subsets during infection and highlights a crucial aspect of host defense against intracellular pathogens.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011502","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T13:31:36Z","timestamp":1708435896000},"page":"e1011502","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Parasite-induced IFN-\u03b3 regulates host defense via CD115 and mTOR-dependent mechanism of tissue-resident macrophage death"],"prefix":"10.1371","volume":"20","author":[{"given":"Andrew T.","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpi","family":"Giri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Safronova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia I.","family":"Eliseeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha 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