Glycosylphosphatidylinositols in malaria pathogenesis and immunity

Potential for therapeutic inhibition and vaccination

C BOUTLIS, Eleanor Riley, Nicholas Anstey, J Desouza

Research output: Contribution to journalArticleResearchpeer-review

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 paradigm that 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. � Springer-Verlag Berlin Heidelberg 2005.
Original languageEnglish
Pages (from-to)145-185
Number of pages41
JournalCurrent Topics in Microbiology and Immunology
Volume297
Publication statusPublished - 2005

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Glycosylphosphatidylinositols
Malaria
Immunity
Vaccination
Plasmodium falciparum
Poisons
Therapeutics
Schizonts
Parasitemia
Second Messenger Systems
Berlin
Eukaryota
Antibody Formation
Immunoglobulin M
Rupture
Membrane Proteins
Parasites
Fever
Immunoglobulin G
Maintenance

Cite this

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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 paradigm that 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. � Springer-Verlag Berlin Heidelberg 2005.",
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Glycosylphosphatidylinositols in malaria pathogenesis and immunity : Potential for therapeutic inhibition and vaccination. / BOUTLIS, C; Riley, Eleanor; Anstey, Nicholas; Desouza, J.

In: Current Topics in Microbiology and Immunology, Vol. 297, 2005, p. 145-185.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Glycosylphosphatidylinositols in malaria pathogenesis and immunity

T2 - Potential for therapeutic inhibition and vaccination

AU - BOUTLIS, C

AU - Riley, Eleanor

AU - Anstey, Nicholas

AU - Desouza, J

PY - 2005

Y1 - 2005

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