Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen.
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.
Safeukui
Innocent
I
Molecular Immunology of Parasites Unit, CNRS URA 2581, Institut Pasteur, Paris, France.
Correas
Jean-Michel
JM
Brousse
Valentine
V
Hirt
Déborah
D
Deplaine
Guillaume
G
Mulé
Sébastien
S
Lesurtel
Mickael
M
Goasguen
Nicolas
N
Sauvanet
Alain
A
Couvelard
Anne
A
Kerneis
Sophie
S
Khun
Huot
H
Vigan-Womas
Inès
I
Ottone
Catherine
C
Molina
Thierry Jo
TJ
Tréluyer
Jean-Marc
JM
Mercereau-Puijalon
Odile
O
Milon
Geneviève
G
David
Peter H
PH
Buffet
Pierre A
PA
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