期刊
BLOOD
卷 112, 期 6, 页码 2520-2528出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-03-146779
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资金
- Institut Pasteur Transverse Research Programs (Paris, France) [85]
- Sanofi Aventis-Ministere de L'Enseignement Superieur et de la Recherche Institut Pasteur
- Fondation pour la Recherche Medicale (Paris, France)
- Research of the IMP Unit
- BioMalPar European Network of Excellence [LSHP-CT-2004-503578]
- Agence Nationale de Recherche sur le SIDA (Paris, France)
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.
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