{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:12:49Z","timestamp":1792843969770,"version":"4.5.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI141602, UG3\/UH3 TR002158"],"award-info":[{"award-number":["AI141602, UG3\/UH3 TR002158"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Cytoadhesion of <jats:italic>Plasmodium falciparum<\/jats:italic>-infected red blood cells is a virulence determinant associated with microvascular obstruction and organ complications. The gastrointestinal tract is a major site of sequestration in fatal cerebral malaria cases and kidney complications are common in severe malaria, but parasite interactions with these microvascular sites are poorly characterized. To study parasite tropism for different microvascular sites, we investigated binding of parasite lines to primary human microvascular endothelial cells from intestine (HIMEC) and peritubular kidney (HKMEC) sites. Of the three major host receptors for <jats:italic>P. falciparum<\/jats:italic>, CD36 had low or negligible expression; endothelial protein C receptor (EPCR) had the broadest constitutive expression; and intercellular adhesion molecule 1 (ICAM-1) was weakly expressed on resting cells and was strongly upregulated by TNF-\u03b1 on primary endothelial cells from the brain, intestine, and peritubular kidney sites. By studying parasite lines expressing <jats:italic>var<\/jats:italic> genes linked to severe malaria, we provide evidence that both the DC8 and Group A EPCR-binding subsets of the <jats:italic>P. falciparum<\/jats:italic> erythrocyte membrane protein 1 (PfEMP1) family encodes binding affinity for brain, intestinal, and peritubular kidney endothelial cells, and that DC8 parasite adhesion was partially dependent on EPCR. Collectively, these findings raise the possibility of a brain-gut-kidney binding axis contributing to multi-organ complications in severe malaria.<\/jats:p>","DOI":"10.3389\/fcimb.2022.813011","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T07:57:11Z","timestamp":1643356631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Plasmodium falciparum Parasite Lines Expressing DC8 and Group A PfEMP1 Bind to Brain, Intestinal, and Kidney Endothelial Cells"],"prefix":"10.3389","volume":"12","author":[{"given":"Luana S.","family":"Ortolan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Avril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl B.","family":"Seydel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00615-16","article-title":"Interaction Between Endothelial Protein C Receptor and Intercellular Adhesion Molecule 1 to Mediate Binding of Plasmodium Falciparum-Infected Erythrocytes to Endothelial Cells","volume":"7","author":"Avril","year":"2016","journal-title":"MBio"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003430","article-title":"DC8 and DC13 Var Genes Associated With Severe Malaria Bind Avidly to Diverse Endothelial Cells","volume":"9","author":"Avril","year":"2013","journal-title":"PloS Pathog."},{"key":"B3","doi-asserted-by":"publisher","first-page":"E1782","DOI":"10.1073\/pnas.1120534109","article-title":"A Restricted Subset of Var Genes Mediates Adherence of Plasmodium Falciparum-Infected Erythrocytes to Brain Endothelial Cells","volume":"109","author":"Avril","year":"2012","journal-title":"Proc. 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