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Transcriptomic profiling revealed that Tim-3\n                      <jats:sup>+<\/jats:sup>\n                      macrophages exhibited enhanced antigen presentation and a proinflammatory phenotype characterized by elevated reactive oxygen species (ROS) and proinflammatory cytokine production. Blockade of Tim-3 in vivo exacerbated disease severity, increased parasitemia, and impaired macrophage phagocytic capacity, without directly affecting T-cell responses. Mechanistically, we identified transforming growth factor-beta (TGF-\u03b2) as a key upstream regulator of Tim-3 expression, as TGF-\u03b2 signaling was suppressed during infection, and its stimulation or inhibition correspondingly upregulated or downregulated Tim-3. Furthermore, TGF-\u03b2-induced Tim-3 upregulation potentiated macrophage phagocytosis of infected red blood cells (iRBCs) and conferred protection against iRBC-induced cell death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our results reveal a novel protective TGF-\u03b2\u2013Tim-3 axis that maintains the phagocytic function of macrophages and immune homeostasis in\n                      <jats:italic>Plasmodium yoelii<\/jats:italic>\n                      NSM infection. These findings highlight Tim-3 on macrophages as a potential therapeutic target for modulating host defense against malaria infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-026-07287-3","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T15:24:53Z","timestamp":1772205893000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TGF-\u03b2 regulated Tim-3 sustains macrophage phagocytic function and confers protection in Plasmodium yoelii NSM-infected mice"],"prefix":"10.1186","volume":"19","author":[{"given":"Xiongyu","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guikuan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjie","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiwen","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shenao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keyu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixia","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingfei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"7287_CR1","doi-asserted-by":"publisher","first-page":"2328","DOI":"10.1016\/S0140-6736(23)01249-7","volume":"402","author":"JR Poespoprodjo","year":"2023","unstructured":"Poespoprodjo JR, Douglas NM, Ansong D, Kho S, Anstey NM. 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