Acquisition of IgG to ICAM-1-Binding DBLβ Domains in the Plasmodium falciparum Erythrocyte Membrane Protein 1 Antigen Family Varies between Groups A, B, and C

Olsen, Rebecca W.; Ecklu-Mensah, Gertrude; Bengtsson, Anja; Ofori, Michael F.; Kusi, Kwadwo Asamoah; Koram, Kwadwo A.; Hviid, Lars; Adams, Yvonne; Jensen, Anja T. R.

doi:10.1128/iai.00224-19

Cited by 17 publications

(9 citation statements)

References 56 publications

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“…In agreement with this, our recent study found that Ghanaian children show a transient increase in IgG reactivity to ICAM-1-binding DBLβ domains two weeks after acute malaria followed by decreased levels six weeks later. As in the present study, our previous work 30 and that of others 16 , 31 did not observe differences in IgG reactivities to DBLβ domains between children of similar age with severe or uncomplicated malaria.…”

Section: Discussionsupporting

confidence: 84%

ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children

Suurbaar

Moussiliou

Tahar

et al. 2022

Sci Rep

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Members of the highly polymorphic Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on the surface of infected erythrocytes (IEs) are important virulence factors, which mediate vascular adhesion of IEs via endothelial host receptors and are targets of naturally acquired immunity. The PfEMP1 family can be divided into clinically relevant subgroups, of which some bind intercellular adhesion molecule 1 (ICAM-1). While the acquisition of IgG specific for ICAM-1-binding DBLβ domains is known to differ between PfEMP1 groups, its ability to induce antibody-dependent cellular phagocytosis (ADCP) is unclear. We therefore measured plasma levels of DBLβ-specific IgG, the ability of such IgG to inhibit PfEMP1-binding to ICAM-1, and its ability to opsonize IEs for ADCP, using plasma from Beninese children with severe (SM) or uncomplicated malaria (UM). IgG specific for DBLβ from group A and B ICAM-1-binding PfEMP1 were dominated by IgG1 and IgG3, and were similar in SM and UM. However, levels of plasma IgG inhibiting ICAM-1-binding of group A DBLβ of PFD1235w was significantly higher in children with UM than SM, and acute UM plasma induced a higher ADCP response than acute SM plasma.

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Section: Discussionsupporting

confidence: 84%

ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children

Suurbaar

Moussiliou

Tahar

et al. 2022

Sci Rep

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“…The P. falciparum lines 3D7 (PFD1235w), HB3 (VAR03, VAR21, and VAR34), BM057, and IT4 (VAR13) were maintained in in vitro blood culture and were selected using antibodies against DBLβ_D4 domains of specific PfEMP1s ( Lennartz et al, 2017 ; Olsen et al, 2019 ; Bengtsson et al, 2013 ). IT4VAR19- and IT4VAR20-IEs were maintained in vitro blood cultures and selected for adhesion to EPCR by flowing parasite cultures (5–10% parasitemia) over EPCR (10 µg/ml)–coated ibidi slides (µ-Slide I 0.8 mm or µ-Slide VI 0.1 mm) for 20 min at a shear stress of 0.5 dyn/cm 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Following incubation, IEs were removed and transferred into fresh blood cultures; parasite growth was monitored by thin smear. Phenotypes were verified by flow cytometry and quantitative PCR as previously described ( Lennartz et al, 2017 ; Olsen et al, 2019 ; Bengtsson et al, 2013 ; Lennartz et al, 2015 ; Joergensen et al, 2010 ).…”

Section: Methodsmentioning

confidence: 99%

“…These group A +CM PfEMP1s are characterized by the presence of a particular motif in their ICAM-1–binding sub-domain (DBLβ), which is absent in non–ICAM-1–binding EPCR–adherent IEs, and in DBLβ of ICAM-1–binding group B and C PfEMP1s (group B UM and C UM ; Fig. S1, B and C ) associated with uncomplicated malaria (UM; Lennartz et al, 2017 ; Olsen et al, 2019 ; Turner et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood–brain barrier in cerebral malaria

Adams

Olsen

Bengtsson

et al. 2021

Journal of Experimental Medicine

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Cerebral malaria (CM) is caused by the binding of Plasmodium falciparum–infected erythrocytes (IEs) to the brain microvasculature, leading to inflammation, vessel occlusion, and cerebral swelling. We have previously linked dual intercellular adhesion molecule-1 (ICAM-1)– and endothelial protein C receptor (EPCR)–binding P. falciparum parasites to these symptoms, but the mechanism driving the pathogenesis has not been identified. Here, we used a 3D spheroid model of the blood–brain barrier (BBB) to determine unexpected new features of IEs expressing the dual-receptor binding PfEMP1 parasite proteins. Analysis of multiple parasite lines shows that IEs are taken up by brain endothelial cells in an ICAM-1–dependent manner, resulting in breakdown of the BBB and swelling of the endothelial cells. Via ex vivo analysis of postmortem tissue samples from CM patients, we confirmed the presence of parasites within brain endothelial cells. Importantly, this discovery points to parasite ingress into the brain endothelium as a contributing factor to the pathology of human CM.

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“…An additional recombinant VAR2CSA protein expressed in suspension-adapted CHO cells (ExpiCHO; ThermoFisher Scientific) was also used [ 31 ]. Finally, 2 recombinant DBLβ domains containing an ICAM-1 binding motif, HB3VAR34 and PFD1235w [ 32 , 33 ], and the domain R0 of glutamate-rich protein (GLURP) [ 34 ], produced in Escherichia coli , were included.…”

Section: Methodsmentioning

confidence: 99%

PfEMP1-Specific Immunoglobulin G Reactivity Among Beninese Pregnant Women With Sickle Cell Trait

Lopez-Perez

Viwami

Seidu

et al. 2021

Open Forum Infectious Diseases

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Background Sickle cell trait (HbAS) protects against severe Plasmodium falciparum malaria, but not against placental malaria (PM). In this study, PfEMP1-specific antibodies were measured in HbAA and HbAS Beninese pregnant women as a proxy of exposure to specific PfEMP1 variants. Methods Plasma samples collected at delivery from 338 HbAA and 63 HbAS women were used to measure IgG levels to six recombinant PfEMP1 proteins and three corresponding native proteins expressed on the infected erythrocyte (IE) surface. IgG-mediated inhibition of VAR2CSA + IEs adhesion to CSA was also tested. Results Levels of PfEMP1-specific IgG were similar in the two groups, except for native IT4VAR09 on IEs, where IgG levels were significantly higher in HbAS women. Adjusted odds ratios for women with positive IgG to HB3VAR06 and PFD1235w suggest a lower risk of infection with these virulent variants among HbAS individuals. The percentage of IEs binding to CSA did not differ between HbAA and HbAS women, but correlated positively with levels of anti-VAR2CSA and parity. Women with PM had lower levels of anti-VAR2CSA-specific IgG and lower IgG-mediated inhibition of IE adhesion to CSA. Conclusions The findings support similar malaria exposure in HbAA and HbAS women and a lack of HbAS-dependent protection against placental infection among pregnant women.

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Acquisition of IgG to ICAM-1-Binding DBLβ Domains in the Plasmodium falciparum Erythrocyte Membrane Protein 1 Antigen Family Varies between Groups A, B, and C

Cited by 17 publications

References 56 publications

ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children

ICAM-1-binding Plasmodium falciparum erythrocyte membrane protein 1 variants elicits opsonic-phagocytosis IgG responses in Beninese children

Plasmodium falciparum erythrocyte membrane protein 1 variants induce cell swelling and disrupt the blood–brain barrier in cerebral malaria

PfEMP1-Specific Immunoglobulin G Reactivity Among Beninese Pregnant Women With Sickle Cell Trait

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