Characterization of the Duffy-Binding-Like Domain of<i>Plasmodium falciparum</i>Blood-Stage Antigen 332

Nilsson, Simon; Moll, Kirsten; Angeletti, Davide; Albrecht, Letusa; Kursula, Inari; Jiang, Ning; Sun, Xin; Berzins, Klavs; Wahlgren, Mats; Chen, Qijun

doi:10.4061/2011/671439

Cited by 11 publications

(9 citation statements)

References 43 publications

(78 reference statements)

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“…The presence of antibodies recognizing the three recombinant proteins were measured by ELISA (enzyme-linked immunosorbent assay) as previously described 57 . Recombinant proteins (5 μg, dissolved in 15 mM Na 2 CO 3 and 35 mM NaHCO 3 , pH 9.6) were coated onto Maxisorp plates (Nunc, Rosklid).…”

Section: Methodsmentioning

confidence: 99%

Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface

Quintana

Ch'ng

Moll

et al. 2018

Sci Rep

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Naturally acquired antibodies to proteins expressed on the Plasmodium falciparum parasitized red blood cell (pRBC) surface steer the course of a malaria infection by reducing sequestration and stimulating phagocytosis of pRBC. Here we have studied a selection of proteins representing three different parasite gene families employing a well-characterized parasite with a severe malaria phenotype (FCR3S1.2). The presence of naturally acquired antibodies, impact on rosetting rate, surface reactivity and opsonization for phagocytosis in relation to different blood groups of the ABO system were assessed in a set of sera from children with mild or complicated malaria from an endemic area. We show that the naturally acquired immune responses, developed during malaria natural infection, have limited access to the pRBCs inside a blood group A rosette. The data also indicate that SURFIN4.2 may have a function at the pRBC surface, particularly during rosette formation, this role however needs to be further validated. Our results also indicate epitopes differentially recognized by rosette-disrupting antibodies on a peptide array. Antibodies towards parasite-derived proteins such as PfEMP1, RIFIN and SURFIN in combination with host factors, essentially the ABO blood group of a malaria patient, are suggested to determine the outcome of a malaria infection.

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Section: Methodsmentioning

confidence: 99%

Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface

Quintana

Ch'ng

Moll

et al. 2018

Sci Rep

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“…Antibodies to the recombinant NTS-DBL1α It4var60 domain were analyzed by ELISA as described [52] . Briefly, maxisorp plates (Nunc, Roskild, Denmark) were coated with 0,2 µg of recombinant antigens over night at 4°C dissolved in 15 mM Na 2 CO 3 and 35 mM NaHCO 3 (pH 9.6).…”

Section: Methodsmentioning

confidence: 99%

B-Cell Epitopes in NTS-DBL1α of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum

et al. 2014

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Plasmodium falciparum is the most lethal of the human malaria parasites. The virulence is associated with the capacity of the infected red blood cell (iRBC) to sequester inside the deep microvasculature where it may cause obstruction of the blood-flow when binding is excessive. Rosetting, the adherence of the iRBC to uninfected erythrocytes, has been found associated with severe malaria and found to be mediated by the NTS-DBL1α-domain of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1). Here we show that the reactivity of plasma of Cameroonian children with the surface of the FCR3S1.2-iRBC correlated with the capacity to disrupt rosettes and with the antibody reactivity with a recombinant PfEMP1 (NTS-DBL1α of IT4var60) expressed by parasite FCR3S1.2. The plasma-reactivity in a microarray, consisting of 96 overlapping 15-mer long peptides covering the NTS-DBL1α domain from IT4var60 sequence, was compared with their capacity to disrupt rosettes and we identified five peptides where the reactivity were correlated. Three of the peptides were localized in subdomain-1 and 2. The other two peptide-sequences were localized in the NTS-domain and in subdomain-3. Further, principal component analysis and orthogonal partial least square analysis generated a model that supported these findings. In conclusion, human antibody reactivity with short linear-peptides of NTS-DBL1α of PfEMP1 suggests subdomains 1 and 2 to hold anti-rosetting epitopes recognized by anti-rosetting antibodies. The data suggest rosetting to be mediated by the variable areas of PfEMP1 but also to involve structurally relatively conserved areas of the molecule that may induce biologically active antibodies.

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“…This model suggests that antigen 332 is also involved in protein trafficking, and in VSAs export 28 . Antigen 332 presents a DBL domain 29 that is recognized by the sera from malaria hyper-immune individuals, suggesting that this domain could be exported at the membrane of the iE, and could be exposed to the immune system 29 30 . However, these and many of the other candidates are involved in iE membrane interactions, and the association may be through their role in the rigidity of the iE, which is known to be associated with pathology.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of Plasmodium falciparum parasites from patients with cerebral and uncomplicated malaria

Bertin

Sabbagh

Argy

et al. 2016

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Plasmodium falciparum is responsible of severe malaria, including cerebral malaria (CM). During its intra-erythrocytic maturation, parasite-derived proteins are expressed, exported and presented at the infected erythrocyte membrane. To identify new CM-specific parasite membrane proteins, we conducted a mass spectrometry-based proteomic study and compared the protein expression profiles between 9 CM and 10 uncomplicated malaria (UM) samples. Among the 1097 Plasmodium proteins identified, we focused on the 499 membrane-associated and hypothetical proteins for comparative analysis. Filter-based feature selection methods combined with supervised data analysis identified a subset of 29 proteins distinguishing CM and UM samples with high classification accuracy. A hierarchical clustering analysis of these 29 proteins based on the similarity of their expression profiles revealed two clusters of 15 and 14 proteins, respectively under- and over-expressed in CM. Among the over-expressed proteins, the MESA protein is expressed at the erythrocyte membrane, involved in proteins trafficking and in the export of variant surface antigens (VSAs), but without antigenic function. Antigen 332 protein is exported at the erythrocyte, also involved in protein trafficking and in VSAs export, and exposed to the immune system. Our proteomics data demonstrate an association of selected proteins in the pathophysiology of CM.

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Characterization of the Duffy-Binding-Like Domain ofPlasmodium falciparumBlood-Stage Antigen 332

Cited by 11 publications

References 43 publications

Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface

Antibodies in children with malaria to PfEMP1, RIFIN and SURFIN expressed at the Plasmodium falciparum parasitized red blood cell surface

B-Cell Epitopes in NTS-DBL1α of PfEMP1 Recognized by Human Antibodies in Rosetting Plasmodium falciparum

Proteomic analysis of Plasmodium falciparum parasites from patients with cerebral and uncomplicated malaria

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