{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T03:41:10Z","timestamp":1775619670335,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011679","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,10,19]],"date-time":"2023-10-19T00:00:00Z","timestamp":1697673600000}}],"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["108869\/Z\/15\/Z"],"award-info":[{"award-number":["108869\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC UK","award":["MC_UU_12010\/10"],"award-info":[{"award-number":["MC_UU_12010\/10"]}]},{"DOI":"10.13039\/501100014748","name":"Clarendon Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014748","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000591","name":"Corpus Christi College","doi-asserted-by":"crossref","award":["A. E. Haigh graduate scholarship"],"award-info":[{"award-number":["A. E. Haigh graduate scholarship"]}],"id":[{"id":"10.13039\/501100000591","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04293\/2020"],"award-info":[{"award-number":["UIDB\/04293\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203803\/Z16\/Z"],"award-info":[{"award-number":["203803\/Z16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106917\/Z\/15\/Z"],"award-info":[{"award-number":["106917\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function. However, the impact of host cell iron scarcity beyond anaemia remains elusive in malaria. To address this, we employed a transgenic mouse model carrying a mutation in the transferrin receptor (\n                    <jats:italic>Tfrc<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Y20H\/Y20H<\/jats:italic>\n                    <\/jats:sup>\n                    ), which limits the ability of cells to internalise iron from plasma. At homeostasis\n                    <jats:italic>Tfrc<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Y20H\/Y20H<\/jats:italic>\n                    <\/jats:sup>\n                    mice appear healthy and are not anaemic. However,\n                    <jats:italic>Tfrc<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Y20H\/Y20H<\/jats:italic>\n                    <\/jats:sup>\n                    mice infected with\n                    <jats:italic>Plasmodium chabaudi chabaudi AS<\/jats:italic>\n                    showed significantly higher peak parasitaemia and body weight loss. We found that\n                    <jats:italic>Tfrc<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Y20H\/Y20H<\/jats:italic>\n                    <\/jats:sup>\n                    mice displayed a similar trajectory of malaria-induced anaemia as wild-type mice, and elevated circulating iron did not increase peak parasitaemia. Instead,\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>chabaudi<\/jats:italic>\n                    infected\n                    <jats:italic>Tfrc<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Y20H\/Y20H<\/jats:italic>\n                    <\/jats:sup>\n                    mice had an impaired innate and adaptive immune response, marked by decreased cell proliferation and cytokine production. Moreover, we demonstrated that these immune cell impairments were cell-intrinsic, as\n                    <jats:italic>ex vivo<\/jats:italic>\n                    iron supplementation fully recovered CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell and B cell function. Despite the inhibited immune response and increased parasitaemia,\n                    <jats:italic>Tfrc<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Y20H\/Y20H<\/jats:italic>\n                    <\/jats:sup>\n                    mice displayed mitigated liver damage, characterised by decreased parasite sequestration in the liver and an attenuated hepatic immune response. Together, these results show that host cell iron scarcity inhibits the immune response but prevents excessive hepatic tissue damage during malaria infection. These divergent effects shed light on the role of iron in the complex balance between protection and pathology in malaria.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011679","type":"journal-article","created":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T13:47:07Z","timestamp":1696859227000},"page":"e1011679","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cellular iron governs the host response to malaria"],"prefix":"10.1371","volume":"19","author":[{"given":"Sarah K.","family":"Wideman","sequence":"first","affiliation":[]},{"given":"Joe N.","family":"Frost","sequence":"additional","affiliation":[]},{"given":"Felix C.","family":"Richter","sequence":"additional","affiliation":[]},{"given":"Caitlin","family":"Naylor","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 M.","family":"Lopes","sequence":"additional","affiliation":[]},{"given":"Nicole","family":"Viveiros","sequence":"additional","affiliation":[]},{"given":"Megan R.","family":"Teh","sequence":"additional","affiliation":[]},{"given":"Alexandra E.","family":"Preston","sequence":"additional","affiliation":[]},{"given":"Natasha","family":"White","sequence":"additional","affiliation":[]},{"given":"Shamsideen","family":"Yusuf","sequence":"additional","affiliation":[]},{"given":"Simon J.","family":"Draper","sequence":"additional","affiliation":[]},{"given":"Andrew E.","family":"Armitage","sequence":"additional","affiliation":[]},{"given":"Tiago L.","family":"Duarte","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-6103","authenticated-orcid":true,"given":"Hal","family":"Drakesmith","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"key":"ppat.1011679.ref001","year":"2022"},{"key":"ppat.1011679.ref002","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cell.2016.07.055","article-title":"Malaria: Biology and Disease.","volume":"167","author":"AF Cowman","year":"2016","journal-title":"Cell"},{"key":"ppat.1011679.ref003","doi-asserted-by":"crossref","first-page":"12727","DOI":"10.1074\/jbc.R117.781823","article-title":"Iron homeostasis: An anthropocentric perspective","volume":"292","author":"R Coffey","year":"2017","journal-title":"J Biol Chem"},{"key":"ppat.1011679.ref004","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1126\/science.1224577","article-title":"Hepcidin and the Iron-Infection 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