Nonimmune immunoglobulin binding and multiple adhesion characterize
            <i>Plasmodium falciparum</i>
            -infected erythrocytes of placental origin

Rasti, Niloofar; Namusoke, Fatuma; Chêne, Arnaud; Chen, Qijun; Staalsøe, Trine; Klinkert, Mo‐Quen; Mirembe, Florence; Kironde, Fred; Wahlgren, Mats

doi:10.1073/pnas.0601519103

Cited by 56 publications

(62 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IEs that sequester in the placenta characteristically adhere to CSA (19), express the PfEMP1 protein VAR2CSA on their surface (11), and bind IgM nonspecifically (13,20). The biological significance of the high VAR2CSA affinity for CSA is well-established, whereas the role of nonspecific IgM binding to VAR2CSA is essentially unknown, although it has been proposed to augment placental IE sequestration (20).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, parasites obtained from pediatric patients with cerebral malaria and severe anemia often express PfEMP1 variants that can form rosettes of uninfected erythrocytes around a central IE (10), and parasites causing placental malaria in pregnant women uniformly express a particular PfEMP1 protein (VAR2CSA) that mediates adhesion to chondroitin sulfate A (CSA) in the intervillous space (11). Noticeably, rosette-forming PfEMP1 proteins (12) and CSA-adhering PfEMP1 proteins (13,14) share the ability to bind nonspecific IgM, although CSA-adhering IEs are not prone to rosette formation (15,16). Although the molecular details of the interaction between rosette-forming PfEMP1 proteins and nonspecific IgM are known in considerable detail (17), the biological significance of the nonspecific IgM binding to PfEMP1 in general, and to VAR2CSA in particular, is essentially unknown (18).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Evasion of immunity to Plasmodium falciparum malaria by IgM masking of protective IgG epitopes in infected erythrocyte surface-exposed PfEMP1

Barfod

Dalgaard

Pleman

et al. 2011

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

View full text Add to dashboard Cite

Plasmodium falciparum malaria is a major cause of mortality and severe morbidity. Its virulence is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family is central to both. Here, we present evidence of a P. falciparum evasion mechanism not previously documented: the masking of PfEMP1-specific IgG epitopes by nonspecific IgM. Nonspecific IgM binding to erythrocytes infected by parasites expressing the PfEMP1 protein VAR2CSA (involved in placental malaria pathogenesis and protective immunity) blocked subsequent specific binding of human monoclonal IgG to the Duffy binding-like (DBL) domains DBL3X and DBL5ε of this PfEMP1 variant. Strikingly, a VAR2CSA-specific monoclonal antibody that binds outside these domains and can inhibit IE adhesion to the specific VAR2CSA receptor chondroitin sulfate A was unaffected. Nonspecific IgM binding protected the parasites from FcγR-dependent phagocytosis of VAR2CSA + IEs, but it did not affect IE adhesion to chondroitin sulfate A or lead to C1q deposition on IEs. Taken together, our results indicate that the VAR2CSA affinity for nonspecific IgM has evolved to allow placenta-sequestering P. falciparum to evade acquired protective immunity without compromising VAR2CSA function or increasing IE susceptibility to complement-mediated lysis. Furthermore, functionally important PfEMP1 epitopes not prone to IgM masking are likely to be particularly important targets of acquired protective immunity to P. falciparum malaria.

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Evasion of immunity to Plasmodium falciparum malaria by IgM masking of protective IgG epitopes in infected erythrocyte surface-exposed PfEMP1

Barfod

Dalgaard

Pleman

et al. 2011

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

View full text Add to dashboard Cite

show abstract

“…The var2csa gene, a member of the P. falciparum var multi-gene family encoding PfEMP-1 proteins expressed on the erythrocyte surface, has been associated with adhesion to CSA in the placenta (Salanti et al 2003;Viebig et al 2005). Interactions with hyaluronic acid and non-immune immunoglobulin G (IgG)/ Fc-γ receptors have also been implicated in the binding of infected erythrocytes to the placenta (Beeson et al 2000;Fried et al 2006;Rasti et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Effect of cytokine treatment on the in vitro expression of the P. falciparum adhesion receptor chondroitin-4-sulphate on the surface of human choriocarcinoma (BeWo) cells

et al. 2007

View full text Add to dashboard Cite

BeWo human choriocarcinoma cells have recently been identified as an in vitro model of adhesion of Plasmodium falciparum-infected erythrocytes to the major placental receptor chondroitn-4-sulphate (CSA). In this study, we show that treatment of BeWo cells with tumour necrosis factor-alpha and/or interferon-gamma, cytokines linked with pregnancy-associated malaria and poor pregnancy outcome, does not alter the expression of cell surface CSA. BeWo cells do not express the common P. falciparum adhesion receptor cluster of differentiation 36 (CD36) on the cell surface, and this was unchanged after treatment with cytokines. These data demonstrate that in vitro cultured BeWo cells mimic the P. falciparum adhesion receptor expression profile of ex vivo placental cytotrophoblast cells.

show abstract

“…Several studies demonstrated that nonspecific IgM antibodies can inhibit parasite adhesion (41,42). To exclude this possibility, total IgG was purified from pools of sera from 6 men, 9 children, and 10 pregnant women.…”

Section: Characteristics Of Participantsmentioning

confidence: 99%

Functional Antibodies against VAR2CSA in Nonpregnant Populations from Colombia Exposed to Plasmodium falciparum and Plasmodium vivax

et al. 2014

View full text Add to dashboard Cite

iIn pregnancy, parity-dependent immunity is observed in response to placental infection with Plasmodium falciparum. Antibodies recognize the surface antigen, VAR2CSA, expressed on infected red blood cells and inhibit cytoadherence to the placental tissue. In most settings of malaria endemicity, antibodies against VAR2CSA are predominantly observed in multigravid women and infrequently in men, children, and nulligravid women. However, in Colombia, we detected antibodies against multiple constructs of VAR2CSA among men and children with acute P. falciparum and Plasmodium vivax infection. The majority of men and children (>60%) had high levels of IgGs against three recombinant domains of VAR2CSA: DBL5, DBL3X, and ID1-ID2. Surprisingly, these antibodies were observed only in pregnant women, men, and children exposed either to P. falciparum or to P. vivax. Moreover, the anti-VAR2CSA antibodies are of high avidity and efficiently inhibit adherence of infected red blood cells to chondroitin sulfate A in vitro, suggesting that they are specific and functional. These unexpected results suggest that there may be genotypic or phenotypic differences in the parasites of this region or in the host response to either P. falciparum or P. vivax infection outside pregnancy. These findings may hold significant clinical relevance to the pathophysiology and outcome of malaria infections in this region.

show abstract

Nonimmune immunoglobulin binding and multiple adhesion characterize Plasmodium falciparum -infected erythrocytes of placental origin

Cited by 56 publications

References 31 publications

Evasion of immunity to Plasmodium falciparum malaria by IgM masking of protective IgG epitopes in infected erythrocyte surface-exposed PfEMP1

Evasion of immunity to Plasmodium falciparum malaria by IgM masking of protective IgG epitopes in infected erythrocyte surface-exposed PfEMP1

Effect of cytokine treatment on the in vitro expression of the P. falciparum adhesion receptor chondroitin-4-sulphate on the surface of human choriocarcinoma (BeWo) cells

Functional Antibodies against VAR2CSA in Nonpregnant Populations from Colombia Exposed to Plasmodium falciparum and Plasmodium vivax

Contact Info

Product

Resources

About