ArticleCellular microbiology2015
Investigating the function of Fc-specific binding of IgM to Plasmodium falciparum erythrocyte membrane protein 1 mediating erythrocyte rosetting.
Article in Cellular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
- Glycopolymer binds pathogenic IgM autoantibodies and pulls them into the mononuclear phagocyte system for degradation.Scientific reports · 2025Article
- Acquisition of Fc-afucosylation of PfEMP1-specific IgG is age-dependent and associated with clinical protection against malaria.Nature communications · 2025Article
- Breaking the bind: PfEMP1-specific antibodies in cerebral malaria.Frontiers in immunology · 2025Review
- Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype.PLoS pathogens · 2025Article
- Profiling the Plasmodium falciparum Erythrocyte Membrane Protein 1-Specific Immununoglobulin G Response Among Ghanaian Children With Hemoglobin S and C.The Journal of infectious diseases · 2024Article
- PfEMP1 and var genes - Still of key importance in Plasmodium falciparum malaria pathogenesis and immunity.Advances in parasitology · 2024Review
- Review
- Cryo-electron microscopy of IgM-VAR2CSA complex reveals IgM inhibits binding of Plasmodium falciparum to Chondroitin Sulfate A.Nature communications · 2023Article
- Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M.Nature communications · 2023Article
- Analysis of allelic cross-reactivity of monoclonal IgG antibodies by a multiplexed reverse FluoroSpot assay.eLife · 2022Article
- Genetics of cerebral malaria: pathogenesis, biomarkers and emerging therapeutic interventions.Cell & bioscience · 2022Review
- Influence of αJournal of blood medicine · 2022Article
- Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination.Nature communications · 2021Article
- Structural basis for placental malaria mediated by Plasmodium falciparum VAR2CSA.Nature microbiology · 2021Article
- PfEMP1 A-Type ICAM-1-Binding Domains Are Not Associated with Cerebral Malaria in Beninese Children.mBio · 2020Article
- Binding of human serum proteins to Plasmodium falciparum-infected erythrocytes and its association with malaria clinical presentation.Malaria journal · 2020Article
- In vitro selection for adhesion of Plasmodium falciparum-infected erythrocytes to ABO antigens does not affect PfEMP1 and RIFIN expression.Scientific reports · 2020Article
- Rosetting revisited: a critical look at the evidence for host erythrocyte receptors inParasitology · 2020Review
- Cerebral Plasmodium falciparum malaria: The role of PfEMP1 in its pathogenesis and immunity, and PfEMP1-based vaccines to prevent it.Immunological reviews · 2020Review
- VAR2CSA-Mediated Host Defense Evasion ofFrontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Acquired protection from Plasmodium falciparum malaria takes years to develop, probably reflecting the ability of the parasites to evade immunity. A recent example of this is the binding of the Fc region of IgM to VAR2CSA-type PfEMP1. This interferes with specific IgG recognition and phagocytosis of opsonized infected erythrocytes (IEs) without compromising the placental IE adhesion mediated by this PfEMP1 type. IgM also binds via Fc to several other PfEMP1 proteins, where it has been proposed to facilitate rosetting (binding of uninfected erythrocytes to a central IE). To further dissect the functional role of Fc -mediated IgM binding to PfEMP1, we studied the PfEMP1 protein HB3VAR06, which mediates rosetting and binds IgM. Binding of IgM to this PfEMP1 involved the Fc domains Cμ3-Cμ4 in IgM and the penultimate DBL domain (DBLζ2) at the C-terminus of HB3VAR06. However, IgM binding did not inhibit specific IgG labelling of HB3VAR06 or shield IgG-opsonized IEs from phagocytosis. Instead, IgM was required for rosetting, and each pentameric IgM molecule could bind two HB3VAR06 molecules. Together, our data indicate that the primary function of Fc -mediated IgM binding in rosetting is not to shield IE from specific IgG recognition and phagocytosis as in VAR2CSA-type PfEMP1. Rather, the function appears to be strengthening of IE-erythrocyte interactions. In conclusion, our study provides new evidence on the molecular details and functional significance of rosetting, a long-recognized marker of parasites that cause severe P. falciparum malaria.
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