{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:11:41Z","timestamp":1788970301967,"version":"build-2803163510"},"reference-count":0,"publisher":"Portland Press Ltd.","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/100015691","name":"HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI070655"],"award-info":[{"award-number":["1R01AI070655"]}],"id":[{"id":"10.13039\/100015691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"HHS | NIH | National Center for Research Resources","doi-asserted-by":"publisher","award":["5G12RR008124-16A1"],"award-info":[{"award-number":["5G12RR008124-16A1"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"HHS | NIH | National Center for Research Resources","doi-asserted-by":"publisher","award":["5G12RR008124-16A1S1"],"award-info":[{"award-number":["5G12RR008124-16A1S1"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Linear, nonreducing terminal a-galactopyranosyl (a-Gal) epitopes are displayed on the major surface glycosylphosphatidylinositol (GPI)-anchored glycoconjugates of infective Trypanosoma cruzi trypomastigotes, the agent of Chagas disease (CD). These immunodominant epitopes elicit abundant (3-5% of circulating IgG), trypanolytic CD anti-a-Gal antibodies, yet their role on the parasite surface remains elusive. Here, affinity purification of macrophage extracts on the immobilized Gal\u03b11-3Gal\u03b21-4GlcNAc\u03b2 (Galili\u2019s aGal epitope) identified Galectin-3 (Gal-3) and the annexin A2-S100A10 heterotetramer (A2t) as candidate host-cell receptors, whose specificities were mapped against glycoconjugates and parasite-derived molecules. Gal-3 bound a-Gal-bearing neoglycoproteins (\u03b1-Gal-NGPs), the glycosphingolipid (GSL) iGb3 (Gal\u03b11-3Gal\u03b21-4Glc\u03b21-1-Cer), trypomastigote-derived GPI-mucins (tGPI-mucins), and glycoinositolphospholipids (tGIPLs).\u00a0 \u03b1-Galactosidase abolished Gal-3 binding to trypomastigotes; epimastigote binding was reduced only by \u03b2-galactosidase. Conversely, A2t bound galactosylated GSLs in calcium-dependent manner, most strongly Gb4 (GalNAc\u03b21-3Gal\u03b11-4Gal\u03b21-4Glc\u03b21-1-Cer), but not \u03b1-Gal-NGPs, and only two of 442 glycans on a printed array gave signals above background, indicating lipid-dependent recognition. A2t recognized the phospholipid-enriched fractions of both developmental stages equally, the tGIPL fraction of trypomastigotes only, and not tGPI-mucins. Antibody blockade of surface Anx2, S100A10, or Gal-3, competition with the soluble proteins, and RNA interference reduced macrophage infection by 29 to 50%, about 53%, and 42 to 59%, respectively. Terminal a-Gal epitopes on major trypomastigote GPI-anchored glycoconjugates therefore contribute to host-cell invasion, chiefly through Gal-3, whereas A2t engages a broader set of lipid-associated ligands; both contribute to a redundant entry repertoire rather than acting as obligate receptors. These interactions may offer targets for vaccine and chemotherapeutic development and serve as diagnostic and prognostic biomarkers in CD.<\/jats:p>","DOI":"10.1042\/bcj20260011","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:30:39Z","timestamp":1788967839000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1-Galactosyl residues on\u00a0\n                    <i>Trypanosoma cruzi\u00a0<\/i>\n                    trypomastigote glycoconjugates contribute to host-cell invasion via Galectin-3 and Annexin A2\u2013S100A10 complex"],"prefix":"10.1042","author":[{"given":"Luciane","family":"Ganiko","sequence":"first","affiliation":[{"name":"The University of Texas at El Paso, El Paso, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto S.","family":"Nakayasu","sequence":"additional","affiliation":[{"name":"Pacific Northwest National Laboratory, Richland, Washington, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"da Silva Ferreira","sequence":"additional","affiliation":[{"name":"The University of Texas at El Paso, El Paso, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz","family":"S. Silva","sequence":"additional","affiliation":[{"name":"Universidade Federal de Sao Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"F. Marques","sequence":"additional","affiliation":[{"name":"University of Southern Mississippi, Hattiesburg, Mississippi, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila","family":"S. G. Farani","sequence":"additional","affiliation":[{"name":"The University of Texas at El Paso, El Paso, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor C.","family":"Almeida","sequence":"additional","affiliation":[{"name":"The University of Texas at El Paso, El Paso, Texas, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,9,9]]},"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/doi\/10.1042\/BCJ20260011\/991952\/bcj-2026-0011.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/doi\/10.1042\/BCJ20260011\/991952\/bcj-2026-0011.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:30:40Z","timestamp":1788967840000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/doi\/10.1042\/BCJ20260011\/238049\/Galactosyl-residues-on-Trypanosoma-cruzi"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1042\/bcj20260011","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"article-number":"BCJ20260011"}}