{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:21:13Z","timestamp":1768814473519,"version":"3.49.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["EQ20170336722"],"award-info":[{"award-number":["EQ20170336722"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-11-LABX-0051"],"award-info":[{"award-number":["ANR-11-LABX-0051"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>The persistence of erythrocytes infected with <jats:italic>Plasmodium falciparum<\/jats:italic> gametocytes in the bloodstream is closely related to the modulation of their mechanical properties. New drugs that increase the stiffness of infected erythrocytes may thus represent a novel approach to block malaria parasite transmission. The phosphodiesterase inhibitor tadalafil has been shown to impair the ability of infected erythrocytes to circulate in an <jats:italic>in vitro<\/jats:italic> model for splenic retention. Here, we used a humanized mouse model to address <jats:italic>in vivo<\/jats:italic> the effect of tadalafil on the circulation kinetics of mature gametocyte-infected erythrocytes. We show that stiff immature gametocyte-infected erythrocytes are retained in the spleen of humanized mice at rates comparable to that of the <jats:italic>in vitro<\/jats:italic> model. Accordingly, tadalafil-induced stiffening of mature gametocyte-infected erythrocytes impairs their circulation in the bloodstream and triggers their retention by the spleen. These <jats:italic>in vivo<\/jats:italic> results validate that tadalafil is a novel drug lead potentially capable of blocking malaria parasite transmission by targeting GIE mechanical properties.<\/jats:p>","DOI":"10.3389\/fcimb.2022.883759","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T07:13:17Z","timestamp":1653462797000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["The Phosphodiesterase Inhibitor Tadalafil Promotes Splenic Retention of Plasmodium falciparum Gametocytes in Humanized Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Daniela","family":"Barbieri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludivine","family":"Royer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Dupuy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Fran\u00e7ois","family":"Franetich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurel","family":"Tefit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Esther","family":"N\u2019Dri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Mazier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Silvie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"Moreno-Sabater","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Lavazec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1182\/blood-2013-08-520767","article-title":"Molecular Evidence for the Localization of Plasmodium Falciparum Immature Gametocytes in Bone Marrow","volume":"123","author":"Aguilar","year":"2014","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1111\/j.1462-5822.2012.01786.x","article-title":"Host Cell Deformability is Linked to Transmission in the Human Malaria Parasite Plasmodium Falciparum","volume":"14","author":"Aingaran","year":"2012","journal-title":"Cell Microbiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1274","DOI":"10.1021\/jm201422e","article-title":"Drug-To-Genome-to-Drug, Step 2: Reversing Selectivity in a Series of Antiplasmodial Compounds","volume":"55","author":"Beghyn","year":"2012","journal-title":"J. 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