{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T07:02:46Z","timestamp":1772434966400,"version":"3.50.1"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      parasites, the causative agents of malaria, undergo a complex liver stage shaped by the spatial heterogeneity of the liver. As one of the most sexually dimorphic organs, the liver undergoes sex-specific immune responses. However, the roles of biological sex and androgens in regulating hepatic host\u2013parasite interactions during\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      infection remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male and female BALB\/cJ mice, including orchiectomized (ORX) and androgen-treated males, were infected with\n                      <jats:italic>Plasmodium yoelii<\/jats:italic>\n                      sporozoites. Hepatic parasite burden, immune cell composition, and gene expression were assessed using immunofluorescence microscopy, RT-PCR, and spatial transcriptomics. Comparisons across sex and androgen status were performed in infected and mock-infected conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Androgens increased parasite survival by reducing elimination of parasite-infected hepatocytes. Females and ORX males exhibited enhanced immune activity during\n                      <jats:italic>P. yoelii<\/jats:italic>\n                      infection, resulting in fewer infected hepatocytes by 44 hours post-infection. At homeostasis, intact males had lower baseline densities of Kupffer cells, monocytes, and dendritic cells, a disparity that persisted and increased during infection. Although infection induced similar fold increases in Kupffer cell numbers across groups, intact males had reduced absolute numbers of Kupffer cells, diminished antigen presentation, and blunted Type I interferon responses compared to female and ORX male mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings indicate that biological sex- and androgen-mediated differences in baseline hepatic innate immune cell composition critically shape immune responses and parasite survival during\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      liver stage infection. Together, our findings highlight the role of biological sex in shaping immune responses during\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      parasite infection in the liver and underscore the importance of considering sex as a biological variable in malaria research.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1734587","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T06:32:41Z","timestamp":1772433161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Host biological sex directs immune control of the Plasmodium parasite liver stage in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Caroline J.","family":"Duncombe","sequence":"first","affiliation":[{"name":"Graduate Program in Pathobiology, Department of Global Health, University of Washington","place":["Seattle, WA, United States"]},{"name":"Department of Laboratory Medicine and Pathology, University of Washington","place":["Seattle, WA, United States"]},{"name":"Center for Emerging and Re-emerging Infectious Diseases (CERID), University of Washington","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alen S.","family":"Poehlman","sequence":"additional","affiliation":[{"name":"Center for Emerging and Re-emerging Infectious Diseases (CERID), University of Washington","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan N.","family":"Conrad","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington","place":["Seattle, WA, United States"]},{"name":"Center for Emerging and Re-emerging Infectious Diseases (CERID), University of Washington","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nilasha","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington","place":["Seattle, WA, United States"]},{"name":"Center for Emerging and Re-emerging Infectious Diseases (CERID), University of Washington","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Ayenew","sequence":"additional","affiliation":[{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca C.","family":"Blyn","sequence":"additional","affiliation":[{"name":"Graduate Program in Pathobiology, Department of Global Health, University of Washington","place":["Seattle, WA, United States"]},{"name":"Center for Global Infectious Disease Research, Seattle Children\u2019s Research Institute","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"GW","family":"McElfresh","sequence":"additional","affiliation":[{"name":"Oregon National Primate Research Center, Oregon Health and Science University","place":["Beaverton, OR, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth K. 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