{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T19:09:17Z","timestamp":1776107357671,"version":"3.50.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"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:p>Hepatopathy is frequently observed in patients with severe malaria but its pathogenesis remains unclear. Galectins are evolutionarily conserved glycan-binding proteins with pleiotropic roles in innate and adaptive immune responses, and exhibit pivotal roles during <jats:italic>Plasmodium<\/jats:italic> spp. infection. Here, we analyzed the impact of blockage of galectin-receptor interactions by treatment with alpha (\u03b1)-lactose on liver immunopathology during the erythrocytic stage of malaria in mice infected with <jats:italic>Plasmodium berghei<\/jats:italic> ANKA (<jats:italic>Pb<\/jats:italic>ANKA). Our results found that compared with <jats:italic>Pb<\/jats:italic>ANKA-infected mice (malarial mice), blockage of galectin-receptor interactions led to decreased host survival rate and increased peripheral blood parasitemia; exacerbated liver pathology, increased numbers of CD68<jats:sup>+<\/jats:sup> macrophages and apoptotic cells, and increased parasite burden in the livers on days 5 and 7 post infection (p.i.) as well as increased mRNA expression levels of galectin-9 (Gal-9) and its receptor, the T cell immunoglobulin domain and mucin domain protein 3 (Tim-3), interferon (IFN)\u03b1, IFN\u03b3, and the triggering receptor expressed on myeloid cells (TREM)-1 in the livers or spleens of <jats:italic>Pb<\/jats:italic>ANKA-infected mice on day 7 p.i. Observed by transmission electron microscopy, the peritoneal macrophages isolated from malarial mice with \u03b1-lactose treatment had more pseudopodia than those from malarial mice. Measured by using quantitative real-time reverse transcription-polymerase chain reaction assay, the mRNA expression levels of Gal-9, IFN\u03b1, IFN\u03b2, IFN\u03b3, and TREM-1 were increased in the peritoneal macrophages isolated from malarial mice with \u03b1-lactose treatment in comparison of those from malarial mice. Furthermore, significant positive correlations existed between the mRNA levels of Gal-9 and Tim-3\/IFN\u03b3\/TREM-1 in both the livers and the peritoneal macrophages, and between Gal-9 and Tim-3\/TREM-1 in the spleens of malarial mice; significant positive correlations existed between the mRNA levels of Gal-9 and IFN\u03b3 in the livers and between Gal-9 and IFN\u03b1 in the peritoneal macrophages from malarial mice treated with \u03b1-lactose. Our data suggest a potential role of galectin-receptor interactions in limiting liver inflammatory response and parasite proliferation by down-regulating the expressions of IFN\u03b1, IFN\u03b3, and TREM-1 during <jats:italic>Pb<\/jats:italic>ANKA infection.<\/jats:p>","DOI":"10.3389\/fimmu.2021.758052","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T22:34:55Z","timestamp":1638311695000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of Galectin-Receptor Interactions on Liver Pathology During the Erythrocytic Stage of Plasmodium berghei Malaria"],"prefix":"10.3389","volume":"12","author":[{"given":"Yifan","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiguang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyu","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangli","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199609123351107","article-title":"The Treatment of Malaria","volume":"335","author":"White","year":"1996","journal-title":"N Engl J 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