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Using a mouse model of infection we discovered liver burden was suppressed in blood-stage experienced, compared to na\u00efve, animals, independently of adaptive responses and inflammation. We observed greater chromatin accessibility of a subset of interferon stimulated genes in blood-stage experienced animals, and a rapid increase in transcription of these genes upon sporozoite challenge.\n                  <jats:italic>Ex vivo<\/jats:italic>\n                  stimulation of hepatocytes from blood-stage experienced mice also led to a rapid and elevated response upon treatment with an unrelated antigen, ctDNA. Taken together, these data are consistent with a model in which hepatocytes are reprogramed by blood stage\n                  <jats:italic>Plasmodium<\/jats:italic>\n                  infection to exhibit trained memory akin to what has been described in innate immune cells. The consequences of training of hepatocytes could be wide-reaching and might alter responses to diverse pathogens and other stimuli.\n                <\/jats:p>","DOI":"10.64898\/2026.07.20.739619","type":"posted-content","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:15:20Z","timestamp":1784866520000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Plasmodium<\/i>\n                  blood-stage induces trained immunity in hepatocytes"],"prefix":"10.64898","author":[{"given":"Elizabeth KK","family":"Glennon","sequence":"first","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinotenda","family":"Tongogara","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhi","family":"Ho","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, WA, USA"},{"name":"University of Washington School of Medicine, Department of Global Health, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica I","family":"Primavera","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Stegman","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lola","family":"Velush","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassandra","family":"Fieldson","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Velychko","sequence":"additional","affiliation":[{"name":"University of Washington, Department of Laboratory Medicine and Pathology, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Subijanto","sequence":"additional","affiliation":[{"name":"University of Washington, Department of Laboratory Medicine and Pathology, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael B.","family":"Polidoro","sequence":"additional","affiliation":[{"name":"Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B. 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