{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:56:30Z","timestamp":1768506990583,"version":"3.49.0"},"posted":{"date-parts":[[2023,6,30]]},"group-title":"Immunology","reference-count":96,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Elemental iron is an essential nutrient involved in many biological processes including infection and immunity. How iron impacts\n                  <jats:italic>Toxoplasma gondii<\/jats:italic>\n                  (\n                  <jats:italic>T. gondii<\/jats:italic>\n                  )\n                  <jats:italic>in vivo<\/jats:italic>\n                  and development of immunity during infection is unclear. We found that although iron is required for parasite proliferation\n                  <jats:italic>in vitro,<\/jats:italic>\n                  paradoxically, iron restriction\n                  <jats:italic>in vivo<\/jats:italic>\n                  increased parasite burdens during acute and persistent infection stages and decreased survival of mice. Iron restriction lowered IL-12 and IFN\n                  <jats:italic>\u03b3<\/jats:italic>\n                  in spleen and serum, but ratios of myeloid cells and the number and function of Natural Killer cells were unchanged. Iron restriction significantly impaired the development of CD4+ and CD8+ T cell responses to\n                  <jats:italic>T. gondii<\/jats:italic>\n                  during replicating type II and attenuated vaccine strain\n                  <jats:italic>cps1-1<\/jats:italic>\n                  infection. Low iron conditions reduced the percent and absolute numbers of antigen experienced CD11a+CD49d+, functional IFN\n                  <jats:italic>\u03b3<\/jats:italic>\n                  +, and CD62L-KLRG1+ effector T cells. Iron restriction also decreased vaccine efficacy of\n                  <jats:italic>cps1-1<\/jats:italic>\n                  strain against secondary lethal challenge. Antigen experienced CD4+ and CD8+ T cells both upregulated their iron transporter Transferrin receptor 1 (CD71) during infection regardless of iron restriction. Mice whose CD4+ T cells were deficient in CD71 had reduced CD4+ T cell antigen experience and polyfunctionality, yet CD8+ T cell responses remained intact, and their long term survival was not affected compared to wild type litter mate controls. This study highlights that iron acquisition by T cells is required for activation and vaccine induced long-term protection against\n                  <jats:italic>T. gondii<\/jats:italic>\n                  . Understanding how iron affects multiple immune compartments will be essential to define iron regulation of immunity to\n                  <jats:italic>T. gondii<\/jats:italic>\n                  .\n                <\/jats:p>","DOI":"10.1101\/2023.06.28.546960","type":"posted-content","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T23:25:11Z","timestamp":1688167511000},"source":"Crossref","is-referenced-by-count":1,"title":["Transferrin Receptor 1 is Required for CD4+ T Cell Iron-Dependent Response During Acute\n                  <i>Toxoplasma gondii<\/i>\n                  Infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0779-2031","authenticated-orcid":false,"given":"Stephen L.","family":"Denton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6692-1852","authenticated-orcid":false,"given":"Tathagato","family":"Roy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hunter K.","family":"Keplinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai K.","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8805-4561","authenticated-orcid":false,"given":"Jason P.","family":"Gigley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024100705450763000_2023.06.28.546960v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2009.04.003"},{"key":"2024100705450763000_2023.06.28.546960v2.2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/157.1.1"},{"key":"2024100705450763000_2023.06.28.546960v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(00)00124-7"},{"key":"2024100705450763000_2023.06.28.546960v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2003.12.001"},{"key":"2024100705450763000_2023.06.28.546960v2.5","doi-asserted-by":"crossref","first-page":"10601","DOI":"10.1016\/S0021-9258(18)81663-5","article-title":"Purine metabolism in Toxoplasma gondii","volume":"264","year":"1989","journal-title":"J Biol Chem"},{"key":"2024100705450763000_2023.06.28.546960v2.6","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E12-11-0827"},{"key":"2024100705450763000_2023.06.28.546960v2.7","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cmet.2016.12.011","article-title":"Serine Is an Essential Metabolite for Effector T Cell Expansion","volume":"25","year":"2017","journal-title":"Cell metabolism"},{"key":"2024100705450763000_2023.06.28.546960v2.8","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3389\/fimmu.2020.00621","article-title":"PRMT5 Is Required for T Cell Survival and Proliferation by Maintaining Cytokine Signaling","volume":"11","year":"2020","journal-title":"Front Immunol"},{"key":"2024100705450763000_2023.06.28.546960v2.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1114965109"},{"key":"2024100705450763000_2023.06.28.546960v2.10","doi-asserted-by":"crossref","unstructured":"Aghabi, D. , M. 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