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During their intraerythrocytic life\u2010cycle stages, malaria parasites, <jats:italic>Plasmodium falciparum<\/jats:italic> (<jats:italic>Pf<\/jats:italic>) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host\u2010derived molecules. These molecules facilitate parasite\u2010parasite and parasite\u2010host interactions to ensure parasite survival.<\/jats:p><jats:p>To date, the number of identified <jats:italic>Pf<\/jats:italic> genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of <jats:italic>Pf<\/jats:italic> glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on <jats:italic>Pf<\/jats:italic>\u2010derived EVs or their involvement in the parasite life\u2010cycle has yet to be reported.<\/jats:p><jats:p>Herein, we show that EVs secreted by <jats:italic>Pf<\/jats:italic>\u2010infected RBCs carry significantly higher sialylated complex <jats:italic>N<\/jats:italic>\u2010glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N\u2010glycoproteins and demonstrate that terminal sialic acid on the <jats:italic>N<\/jats:italic>\u2010glycans is essential for uptake by human monocytes. Our results provide the first evidence that <jats:italic>Pf<\/jats:italic> exploits host sialylated <jats:italic>N<\/jats:italic>\u2010glycans to mediate EV uptake by the human immune system cells.<\/jats:p>","DOI":"10.1002\/jex2.33","type":"journal-article","created":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T07:10:07Z","timestamp":1647846607000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Sialylated <i>N<\/i>\u2010glycans mediate monocyte uptake of extracellular vesicles secreted from <i>Plasmodium falciparum<\/i>\u2010infected red blood cells"],"prefix":"10.1002","volume":"1","author":[{"given":"Hila","family":"Ben Ami Pilo","sequence":"first","affiliation":[{"name":"Faculty of Biochemistry Department of Biomolecular Sciences Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Khan 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