title: Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen.
abstract: The current paradigm in Plasmodium falciparum malaria pathogenesis states that young, ring-infected erythrocytes (rings) circulate in peripheral blood and that mature stages are sequestered in the vasculature, avoiding clearance by the spleen. Through ex vivo perfusion of human spleens, we examined the interaction of this unique blood-filtering organ with P falciparum-infected erythrocytes. As predicted, mature stages were retained. However, more than 50% of rings were also retained and accumulated upstream from endothelial sinus wall slits of the open, slow red pulp microcirculation. Ten percent of rings were retained at each spleen passage, a rate matching the proportion of blood flowing through the slow circulatory compartment established in parallel using spleen contrast-enhanced ultrasonography in healthy volunteers. Rings displayed a mildly but significantly reduced elongation index, consistent with a retention process, due to their altered mechanical properties. This raises the new paradigm of a heterogeneous ring population, the less deformable subset being retained in the spleen, thereby reducing the parasite biomass that will sequester in vital organs, influencing the risk of severe complications, such as cerebral malaria or severe anemia. Cryptic ring retention uncovers a new role for the spleen in the control of parasite density, opening novel intervention opportunities.
authors.affiliation: Molecular Immunology of Parasites Unit, CNRS URA 2581, Institut Pasteur, Paris, France.
authors.forename: Innocent
authors.initials: I
authors.lastname: Safeukui
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Correas
authors.forename: Valentine
authors.initials: V
authors.lastname: Brousse
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deplaine
authors.forename: Sébastien
authors.initials: S
authors.lastname: Mulé
authors.forename: Mickael
authors.initials: M
authors.lastname: Lesurtel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goasguen
authors.forename: Alain
authors.initials: A
authors.lastname: Sauvanet
authors.forename: Anne
authors.initials: A
authors.lastname: Couvelard
authors.forename: Sophie
authors.initials: S
authors.lastname: Kerneis
authors.forename: Huot
authors.initials: H
authors.lastname: Khun
authors.forename: Inès
authors.initials: I
authors.lastname: Vigan-Womas
authors.forename: Catherine
authors.initials: C
authors.lastname: Ottone
authors.forename: Thierry Jo
authors.initials: TJ
authors.lastname: Molina
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Peter H
authors.initials: PH
authors.lastname: David
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Buffet
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D066298:In Vitro Techniques; D008833:Microcirculation / Q000469:parasitology*; D010477:Perfusion; D010963:Plasmodium falciparum; D012039:Regional Blood Flow; D013154:Spleen / Q000098:blood supply* / Q000469:parasitology