Abstract
Protective immunity to malaria depends on acquisition of parasite-specific antibodies, with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) being one of the most important target antigens. The effector functions of PfEMP1-specific IgG include inhibition of infected erythrocyte (IE) sequestration and opsonization of IEs for cell-mediated destruction. IgG glycosylation modulates antibody functionality, with increased affinity to FcγRIIIa for IgG lacking fucose in the Fc region (Fc-afucosylation). We report here that selective Fc-afucosylation of PfEMP1-specific IgG1 increases with age in P. falciparum-exposed children and is associated with reduced risk of anemia, independent of the IgG levels. A similar association was found for children having PfEMP1-specific IgG1 inducing multiple effector functions against IEs, particularly those associated with antibody-dependent cellular cytotoxicity (ADCC) by NK cells. Our findings provide new insights regarding protective immunity to P. falciparum malaria and highlight the importance of cell-mediated destruction of IgG-opsonized IEs.
Original language | English |
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Article number | 237 |
Journal | Nature Communications |
Volume | 16 |
Issue number | 1 |
Number of pages | 12 |
ISSN | 2041-1723 |
DOIs | |
Publication status | Published - 2025 |
Bibliographical note
© 2024. The Author(s).Keywords
- Humans
- Immunoglobulin G/immunology
- Malaria, Falciparum/immunology
- Protozoan Proteins/immunology
- Plasmodium falciparum/immunology
- Child
- Child, Preschool
- Antibodies, Protozoan/immunology
- Immunoglobulin Fc Fragments/immunology
- Erythrocytes/parasitology
- Antibody-Dependent Cell Cytotoxicity/immunology
- Glycosylation
- Female
- Male
- Infant
- Fucose/metabolism
- Age Factors
- Killer Cells, Natural/immunology
- Receptors, IgG/metabolism
- Adolescent
- Adult