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  • Association of early interferon-γ production with immunity to clinical malaria: a longitudinal study among Papua New Guinean children

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    Author(s)
    C. D⿿Ombrain, Marthe
    J. Robinson, Leanne
    I. Stanisic, Danielle
    Taraika, Jack
    Bernard, Nicholas
    Michon, Pascal
    Mueller, Ivo
    Schofield, Louis
    Griffith University Author(s)
    Stanisic, Danielle
    Year published
    2008
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    Abstract
    Background. Elucidating the cellular and molecular basis of naturally acquired immunity to Plasmodium falciparum infection would assist in developing a rationally based malaria vaccine. Innate, intermediate, and adaptive immune mechanisms are all likely to contribute to immunity. Interferon-g (IFN-g) has been implicated in both protection against and the pathogenesis of malaria in humans. In addition, considerable heterogeneity exists among rapid IFN-g responses to P. falciparum in malaria-naive donors. The question remains whether similar heterogeneity is observed in malaria-exposed individuals and whether high, medium, ...
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    Background. Elucidating the cellular and molecular basis of naturally acquired immunity to Plasmodium falciparum infection would assist in developing a rationally based malaria vaccine. Innate, intermediate, and adaptive immune mechanisms are all likely to contribute to immunity. Interferon-g (IFN-g) has been implicated in both protection against and the pathogenesis of malaria in humans. In addition, considerable heterogeneity exists among rapid IFN-g responses to P. falciparum in malaria-naive donors. The question remains whether similar heterogeneity is observed in malaria-exposed individuals and whether high, medium, or low IFN-g responsiveness is differentially associated with protective immunity or morbidity. Methods. A 6-month longitudinal cohort study involving 206 school-aged Papua New Guinean children was performed. Peripheral blood mononuclear cells collected at baseline were exposed to live P. falciparum-infected erythrocytes. Early IFN-g responses were measured, and IFN-g-expressing cells were characterized by flow cytometry. IFN-g responsiveness was then tested for associations with parasitological and clinical outcome variables. Results. Malaria-specific heterogeneity in early IFN-g responsiveness was observed among children. High-level early IFN-g responses were associated with protection from high-density and clinical P. falciparum infections. Parasite-induced early IFN-g was predominantly derived from gd T cells (68% of which expressed the natural killer marker CD56) and ab T cells, whereas natural killer cells and other cells made only minor contributions. The expression of CD56 in malaria-responsive, IFN-g-expressing gd T cells correlated with IFN-g responsiveness. Conclusions. High, early IFN-g production by live parasite-stimulated peripheral blood mononuclear cells is a correlate of immunity to symptomatic malaria in Papua New Guinean children, and natural killer-like gd T cells may contribute to protection.
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    Journal Title
    Clinical Infectious Diseases
    Volume
    47
    Issue
    11
    DOI
    https://doi.org/10.1086/592971
    Copyright Statement
    © 2008 by University of Chicago Press. The attached file is reproduced here in accordance with the copyright policy of the publisher. First published in Clinical Infectious Diseases with publishing partner Infectious Diseases Society of America. Please refer to the journal's website for access to the definitive, published version.
    Subject
    Biological sciences
    Biomedical and clinical sciences
    Cellular immunology
    Publication URI
    http://hdl.handle.net/10072/38545
    Collection
    • Journal articles

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