The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology

Buffet, Pierre; Safeukui, Innocent; Deplaine, Guillaume; Brousse, Valentine; Prendki, Virginie; Thellier, Marc; Turner, Gareth D. H.; Mercereau‐Puijalon, Odile

doi:10.1182/blood-2010-04-202911

Cited by 304 publications

(350 citation statements)

References 90 publications

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“…Taken together, these observations strengthen the assumption that subtle but measurable mechanical alterations induce the retention of senescent RBC in the spleen [5]. Measuring the elongation index of circulating RBC is physiologically relevant, requires only small volumes of blood, and provides reproducible, operator-independent results [2]. We agree with Lammers et al that large studies spanning the wide range of diseases associated with impaired splenic function [6] are warranted.…”

Section: Reduced Deformability Of Circulating Erythrocytes: a Marker supporting

confidence: 87%

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Reduced deformability of circulating erythrocytes: A marker of hyposplenism

et al. 2012

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Section: Reduced Deformability Of Circulating Erythrocytes: a Marker supporting

confidence: 87%

“…As the spleen mechanically retains altered red blood cells (RBC) [2], blood samples from hyposplenic patients are expected to contain an excess of poorly deformable RBC. We thus used two techniques in our study: rotational ektacytometry (LORCA) and microsphiltration.…”

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confidence: 99%

Reduced deformability of circulating erythrocytes: A marker of hyposplenism

et al. 2012

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“…Malarial anemia evolves through extravascular elimination of unparasitized erythrocytes by splenic macrophages, concomitant with bone marrow dysfunction and ineffective erythropoiesis [1][2][3]. Early studies demonstrated a shortened lifespan of platelets [4] and uninfected erythrocytes [5] in non-immune patients with falciparum malaria [6].…”

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confidence: 99%

Malarial anemia: digestive vacuole of Plasmodium falciparum mediates complement deposition on bystander cells to provoke hemophagocytosis

Dasari

Fries

Heber

et al. 2014

Med Microbiol Immunol

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“…A number of potential innate control mechanisms have been suggested. In particular, the mechanical removal of pRBCs by the spleen (8,(15)(16)(17)(18) [or liver (19)] is believed to be a primary mechanism by which the host controls the PMF (12). However, few studies have attempted to directly measure host removal of pRBCs in vivo (13,19).…”

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Host-mediated impairment of parasite maturation during blood-stage Plasmodium infection

Khoury

Cromer

Akter

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Severe malaria and associated high parasite burdens occur more frequently in humans lacking robust adaptive immunity to Plasmodium falciparum. Nevertheless, the host may partly control blood-stage parasite numbers while adaptive immunity is gradually established. Parasite control has typically been attributed to enhanced removal of parasites by the host, although in vivo quantification of this phenomenon remains challenging. We used a unique in vivo approach to determine the fate of a single cohort of semisynchronous, Plasmodium berghei ANKA-or Plasmodium yoelii 17XNL-parasitized red blood cells (pRBCs) after transfusion into naive or acutely infected mice. As previously shown, acutely infected mice, with ongoing splenic and systemic inflammatory responses, controlled parasite population growth more effectively than naive controls. Surprisingly, however, this was not associated with accelerated removal of pRBCs from circulation. Instead, transfused pRBCs remained in circulation longer in acutely infected mice. Flow cytometric assessment and mathematical modeling of intraerythrocytic parasite development revealed an unexpected and substantial slowing of parasite maturation in acutely infected mice, extending the life cycle from 24 h to 40 h. Importantly, impaired parasite maturation was the major contributor to control of parasite growth in acutely infected mice. Moreover, by performing the same experiments in rag1 −/− mice, which lack T and B cells and mount weak inflammatory responses, we revealed that impaired parasite maturation is largely dependent upon the host response to infection. Thus, impairment of parasite maturation represents a host-mediated, immune system-dependent mechanism for limiting parasite population growth during the early stages of an acute blood-stage Plasmodium infection. malaria | clearance | mathematical modelling | Plasmodium berghei ANKA | parasite maturation

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The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology

Abstract: Clinical manifestations of

Cited by 304 publications

References 90 publications

Reduced deformability of circulating erythrocytes: A marker of hyposplenism

Reduced deformability of circulating erythrocytes: A marker of hyposplenism

Malarial anemia: digestive vacuole of Plasmodium falciparum mediates complement deposition on bystander cells to provoke hemophagocytosis

Host-mediated impairment of parasite maturation during blood-stage Plasmodium infection

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