Plasmodium falciparum has evolved multiple mechanisms to hijack human immunoglobulin M.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 05 2023
08 05 2023
Historique:
received:
02
11
2022
accepted:
25
04
2023
medline:
10
5
2023
pubmed:
9
5
2023
entrez:
8
5
2023
Statut:
epublish
Résumé
Plasmodium falciparum causes the most severe malaria in humans. Immunoglobulin M (IgM) serves as the first line of humoral defense against infection and potently activates the complement pathway to facilitate P. falciparum clearance. A number of P. falciparum proteins bind IgM, leading to immune evasion and severe disease. However, the underlying molecular mechanisms remain unknown. Here, using high-resolution cryo-electron microscopy, we delineate how P. falciparum proteins VAR2CSA, TM284VAR1, DBLMSP, and DBLMSP2 target IgM. Each protein binds IgM in a different manner, and together they present a variety of Duffy-binding-like domain-IgM interaction modes. We further show that these proteins interfere directly with IgM-mediated complement activation in vitro, with VAR2CSA exhibiting the most potent inhibitory effect. These results underscore the importance of IgM for human adaptation of P. falciparum and provide critical insights into its immune evasion mechanism.
Identifiants
pubmed: 37156765
doi: 10.1038/s41467-023-38320-z
pii: 10.1038/s41467-023-38320-z
pmc: PMC10167334
doi:
Substances chimiques
Protozoan Proteins
0
Antigens, Protozoan
0
Immunoglobulin M
0
Antibodies, Protozoan
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2650Informations de copyright
© 2023. The Author(s).
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