Glycosylphosphatidylinositol anchors of Plasmodium falciparum: Molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis

Ramachandra S. Naik, Ora Lee H. Branch, Amina S. Woods, Matam Vijaykumar, Douglas J. Perkins, Bernard L. Nahlen, Altaf A. Lal, Robert J. Cotter, Catherine E. Costello, Christian F. Ockenhouse, Eugene A. Davidson, D. Channe Gowda

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Abstract

Induction of proinflammatory cytokine responses by glycosylphosphatidylinositols (GPIs) of intraerythrocytic Plasmodium falciparum is believed to contribute to malaria pathogenesis. In this study, we purified the GPIs of P. falciparum to homogeneity and determined their structures by biochemical degradations and mass spectrometry. The parasite GPIs differ from those of the host in that they contain palmitic (major) and myristic (minor) acids at C-2 of inositol, predominandy C18:0 and C18:1 at sn-1 and sn-2, respectively, and do not contain additional phosphoethanolamine substitution in their core glycan structures. The purified parasite GPIs can induce tumor necrosis factor α release from macrophages. We also report a new finding that adults who have resistance to clinical malaria contain high levels of persistent anti-GPI antibodies, whereas susceptible children lack or have low levels of short-lived antibody response. Individuals who were not exposed to the malaria parasite completely lack anti-GPI antibodies. Absence of a persistent anti-GPI antibody response correlated with malaria-specific anemia and fever, suggesting that anti-GPI antibodies provide protection against clinical malaria. The antibodies are mainly directed against the acylated phosphoinositol portion of GPIs. These results are likely to be valuable in studies aimed at the evaluation of chemically defined structures for toxicity versus immunogenicity with implications for the development of GPI-based therapies or vaccines.

Original languageEnglish (US)
Pages (from-to)1563-1575
Number of pages13
JournalJournal of Experimental Medicine
Volume192
Issue number11
DOIs
StatePublished - Dec 4 2000

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Naik, R. S., Branch, O. L. H., Woods, A. S., Vijaykumar, M., Perkins, D. J., Nahlen, B. L., Lal, A. A., Cotter, R. J., Costello, C. E., Ockenhouse, C. F., Davidson, E. A., & Gowda, D. C. (2000). Glycosylphosphatidylinositol anchors of Plasmodium falciparum: Molecular characterization and naturally elicited antibody response that may provide immunity to malaria pathogenesis. Journal of Experimental Medicine, 192(11), 1563-1575. https://doi.org/10.1084/jem.192.11.1563