Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind

Sherman, Irwin W.; Eda, Shigetoshi; Winograd, Enrique

doi:10.1016/s1286-4579(03)00162-x

Cited by 180 publications

(145 citation statements)

References 79 publications

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“…I nfected red blood cells (irbc) of many species of malaria parasites adhere to the endothelial cells of the microvasculature of numerous deep tissues (1,2). Termed sequestration, this characteristic may facilitate parasite multiplication, avoiding removal of the irbc by the spleen (3,4).…”

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Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration

Franke-Fayard

Janse

Cunha-Rodrigues

et al. 2005

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

286

341

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Sequestration of malaria-parasite-infected erythrocytes in the microvasculature of organs is thought to be a significant cause of pathology. Cerebral malaria (CM) is a major complication of Plasmodium falciparum infections, and PfEMP1-mediated sequestration of infected red blood cells has been considered to be the major feature leading to CM-related pathology. We report a system for the real-time in vivo imaging of sequestration using transgenic luciferase-expressing parasites of the rodent malaria parasite Plasmodium berghei. These studies revealed that: (i) as expected, lung tissue is a major site, but, unexpectedly, adipose tissue contributes significantly to sequestration, and (ii) the class II scavenger-receptor CD36 to which PfEMP1 can bind is also the major receptor for P. berghei sequestration, indicating a role for alternative parasite ligands, because orthologues of PfEMP1 are absent from rodent malaria parasites, and, importantly, (iii) cerebral complications still develop in the absence of CD36-mediated sequestration, dissociating parasite sequestration from CM-associated pathology. Realtime in vivo imaging of parasitic processes may be used to evaluate the molecular basis of pathology and develop strategies to prevent pathology.imaging ͉ Plasmodium ͉ P. berghei ͉ luciferase ͉ real-time in vivo imaging I nfected red blood cells (irbc) of many species of malaria parasites adhere to the endothelial cells of the microvasculature of numerous deep tissues (1, 2). Termed sequestration, this characteristic may facilitate parasite multiplication, avoiding removal of the irbc by the spleen (3, 4). In some parasite-host combinations, the process of sequestration is associated with pathogenesis, for example, Plasmodium falciparum in humans (1, 2, 5) and Plasmodium berghei in certain mouse strains (6, 7). Cerebral malaria (CM) is a major complication of P. falciparum infections, and the sequestration of irbc has been considered to be the major feature leading to CM-related pathology. Sequestration may lead to vascular obstruction, local endothelial cell activation, and the release of proinflammatory cytokines, resulting in damage to adjacent tissues (2, 7, 8). In P. falciparum, the class II scavenger receptor CD36 is a major endothelial receptor. CD36 is involved in not only the adherence of irbc (1, 9, 10) through specific domains of the surface variant antigen PfEMP-1 but also in the modulation of innate and adaptive immune responses (11,12). To date, most investigations of the dynamics of irbc-receptor interactions rely on in vitro observations with cultured cells and immobilized receptors (2). Despite the increase in knowledge of the molecules involved in the binding of irbc to endothelial cells, the specific interactions that lead to pathology have yet to be established. Infection with P. berghei in laboratory rodents is a well established model for the investigation of associations among CM, proinflammatory cytokines, and endothelial receptors involved in the sequestration of irbc, leukocytes, and platelet...

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confidence: 99%

Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration

Franke-Fayard

Janse

Cunha-Rodrigues

et al. 2005

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

286

341

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“…The best documented changes occur as P. falciparum matures to the trophozoite (24-36 h) and schizont (36-48 h) stages, when Pf-RBCs display decreased membrane deformability (2-6), become spherical, and develop cytoadherence properties responsible for parasite sequestration in the postcapillary venules of different organs (7,8). In contrast, during early parasite development, ring-stage (0-24 h after invasion) Pf-RBCs preserve their biconcave shape, can circulate in peripheral blood (9), and thus are exposed to the spleen red pulp. Ring-stage Pf-RBCs may pass through this spleen compartment, be expelled from circulation, or return to the circulation once the parasite has been removed (10).…”

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Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum

Mills¹,

Diez-Silva

Quinn

et al. 2007

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

177

166

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During intraerythrocytic development, Plasmodium falciparum exports proteins that interact with the host cell plasma membrane and subplasma membrane-associated spectrin network. Parasiteexported proteins modify mechanical properties of host RBCs, resulting in altered cell circulation. In this work, optical tweezers experiments of cell mechanical properties at normal physiological and febrile temperatures are coupled, for the first time, with targeted gene disruption techniques to measure the effect of a single parasite-exported protein on host RBC deformability. We investigate Pf155/Ring-infected erythrocyte surface antigen (RESA), a parasite protein transported to the host spectrin network, on deformability of ring-stage parasite-harboring human RBCs. Using a set of parental, gene-disrupted, and revertant isogenic clones, we found that RESA plays a major role in reducing deformability of host cells at the early ring stage of parasite development, but not at more advanced stage. We also show that the effect of RESA on deformability is more pronounced at febrile temperature, which ring-stage parasite-harboring RBCs can be exposed to during a malaria attack, than at normal body temperature. malaria ͉ erythrocyte ͉ membrane shear modulus ͉ spectrin ͉ cytoskeleton A fter Plasmodium falciparum merozoite invasion of a human RBC, the parasite differentiates and multiplies for 48 h, leading to rupture of the parasitized RBC (Pf-RBCs) and release of new merozoites in the blood circulation. Throughout this 48-h period, several parasite proteins are introduced into the RBC plasma membrane and submembranous protein skeleton, thereby modifying a range of structural and functional properties of the Pf-RBCs (1-4). The best documented changes occur as P. falciparum matures to the trophozoite (24-36 h) and schizont (36-48 h) stages, when Pf-RBCs display decreased membrane deformability (2-6), become spherical, and develop cytoadherence properties responsible for parasite sequestration in the postcapillary venules of different organs (7,8). In contrast, during early parasite development, ring-stage (0-24 h after invasion) Pf-RBCs preserve their biconcave shape, can circulate in peripheral blood (9), and thus are exposed to the spleen red pulp. Ring-stage Pf-RBCs may pass through this spleen compartment, be expelled from circulation, or return to the circulation once the parasite has been removed (10). Although the relative importance of these different processes and their underlying mechanisms are not fully understood, it is likely that altered deformability of ring-stage Pf-RBCs (11) plays a crucial role in determining Pf-RBCs spleen processing.Introduction of parasite components within the Pf-RBC membrane and cortical cytoskeleton begins soon after RBC invasion, as demonstrated for the well characterized parasite protein Pf155/Ring-infected erythrocyte surface antigen (RESA) (12). This protein is discharged by the invading merozoite and exported to the Pf-RBC membrane where, once phosphorylated, it interacts with the spectrin n...

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“…[3][4][5][6][7][8][9][10][11][12] The array of different adhesive mechanisms used by the parasite seems to confer a selective advantage for its efficient survival in the host by switching from one adherent type to another as the host develops adhesion inhibitory antibodies and other phenotype-specific immunity. Thus, in malaria endemic areas, almost all individuals by adulthood develop immunity that effectively controls infection and avoid pathogenesis.…”

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confidence: 99%

“…[1][2][3] Although several factors are likely to contribute to the virulence of P. falciparum, it is widely thought that sequestration of parasite-infected red blood cells (IRBCs) in the microvascular capillaries of vital organs plays a central role. [3][4][5][6][7][8][9][10][11][12] The IRBC sequestration has been reported to be mediated by endothelial cell adhesion molecules, such as thrombospondin, CD36, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, P-selectin, and platelet endothelial cell adhesion molecule/ CD31. [3][4][5][6][7][8][9][10][11][12] The array of different adhesive mechanisms used by the parasite seems to confer a selective advantage for its efficient survival in the host by switching from one adherent type to another as the host develops adhesion inhibitory antibodies and other phenotype-specific immunity.…”

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confidence: 99%

Chondroitin Sulfate Proteoglycan but Not Hyaluronic Acid Is the Receptor for the Adherence of Plasmodium falciparum-Infected Erythrocytes in Human Placenta, and Infected Red Blood Cell Adherence Up-Regulates the Receptor Expression

Muthusamy

Achur

Valiyaveettil

et al. 2007

The American Journal of Pathology

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A low-sulfated chondroitin sulfate proteoglycan (CSPG) has been shown to be the receptor for the adherence of Plasmodium falciparum-infected red blood cells (IRBCs) in human placenta. Recently, hyaluronic acid (HA) has been suggested as an additional receptor even though IRBC binding to HA and the presence of HA at locations where IRBCs adhere in the placenta have not been established. In this study, we investigated whether HA is also a receptor for IRBC binding. IRBCs from infected placentas as well as those from different laboratory strains could bind to CSPG but not to HA. In a cell depletion assay, IRBCs from infected placentas could bind quantitatively to CSPG. Although CSPG is present both in the intervillous space and on the syncytiotrophoblast surface, HA is absent in these locations. These data conclusively demonstrate that CSPG, but not HA, is a receptor for IRBC adherence in the placenta. Our data also show, for the first time, that the IRBC-binding CSPG in the placenta is of fetal origin and that, in P. falciparum-infected placentas, the CSPG level is significantly increased, which could exacerbate IRBC adherence and placental pathogenesis. These results have important implications for the development of Of the estimated 2 to 3 million annual fatalities attributable to malaria, Ͼ90% of death is caused by Plasmodium falciparum, the most virulent among the four protozoan parasites that cause malaria in humans.1-3 Although several factors are likely to contribute to the virulence of P. falciparum, it is widely thought that sequestration of parasite-infected red blood cells (IRBCs) in the microvascular capillaries of vital organs plays a central role.3-12 The IRBC sequestration has been reported to be mediated by endothelial cell adhesion molecules, such as thrombospondin, CD36, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, P-selectin, and platelet endothelial cell adhesion molecule/ CD31. [3][4][5][6][7][8][9][10][11][12] The array of different adhesive mechanisms used by the parasite seems to confer a selective advantage for its efficient survival in the host by switching from one adherent type to another as the host develops adhesion inhibitory antibodies and other phenotype-specific immunity. Thus, in malaria endemic areas, almost all individuals by adulthood develop immunity that effectively controls infection and avoid pathogenesis. However, in the case of women during pregnancy, placenta expresses a new receptor that was previously unavailable for IRBC adherence.

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Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind

Cited by 180 publications

References 79 publications

Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration

Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration

Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum

Chondroitin Sulfate Proteoglycan but Not Hyaluronic Acid Is the Receptor for the Adherence of Plasmodium falciparum-Infected Erythrocytes in Human Placenta, and Infected Red Blood Cell Adherence Up-Regulates the Receptor Expression

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