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Glycosylphosphatidylinositols in Malaria Pathogenesis and Immunity: Potential for Therapeutic Inhibition and Vaccination

  • Chapter
Immunology and Immunopathogenesis of Malaria

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 297))

Abstract

Glycosylphosphatidylinositols (GPIs) are found in the outer cell membranes of all eukaryotes. GPIs anchor a diverse range of proteins to the surface of Plasmodium falciparum, but may also exist free of protein attachment. In vitro and in vivo studies have established GPIs as likely candidate toxins in malaria, consistent with the prevailing paradigmthat attributes induction of inflammatory cytokines, fever and other pathology to parasite toxins released when schizonts rupture. Although evolutionarily conserved, sufficient structural differences appear to exist that impart upon plasmodial GPIs the ability to activate second messengers in mammalian cells and elicit immune responses. In populations exposed to P. falciparum, the antibody response to purified GPIs is characterised by a predominance of immunoglobulin (Ig)G over IgM and an increase in the prevalence, level and persistence of responses with increasing age. It remains unclear, however, if these antibodies or other cellular responses to GPIs mediate anti-toxic immunity in humans; anti-toxic immunity may comprise either reduction in the severity of disease or maintenance of the malaria-tolerant state (i.e. persistent asymptomatic parasitaemia). P. falciparum GPIs are potentially amenable to specific therapeutic inhibition and vaccination;more needs to be known about their dual roles in malaria pathogenesis and protection for these strategies to succeed.

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  1. International Health Program, Infectious Diseases Division, Menzies School of Health Research, P.O. Box 41096, 0811, Casuarina, NT, Australia

    C. S. Boutlis & N. M. Anstey

  2. Charles Darwin University, 0909, Darwin, NT, Australia

    C. S. Boutlis & N. M. Anstey

  3. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK

    E. M. Riley & J. B. de Souza

  4. Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Research, 46 Cleveland Street, London, WIT 4JF, UK

    J. B. de Souza

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  1. C. S. Boutlis
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  1. Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Jean Langhorne PhD

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Boutlis, C.S., Riley, E.M., Anstey, N.M., de Souza, J.B. (2005). Glycosylphosphatidylinositols in Malaria Pathogenesis and Immunity: Potential for Therapeutic Inhibition and Vaccination. In: Langhorne, J. (eds) Immunology and Immunopathogenesis of Malaria. Current Topics in Microbiology and Immunology, vol 297. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-29967-X_5

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