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  • Cellular Tumor Necrosis Factor, Gamma Interferon, and Interleukin-6 Responses as Correlates of Immunity and Risk of Clinical Plasmodium falciparum Malaria in Children from Papua New Guinea

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    Author(s)
    J. Robinson, Leanne
    C. D⿿Ombrain, Marthe
    I.Stanisic, Danielle
    Taraika, Jack
    Bernard, Nicholas
    S. Richards, Jack
    G. Beeson, James
    Tavul, Livingstone
    Michon, Pascal
    Mueller, Ivo
    Schofield, Louis
    Griffith University Author(s)
    Stanisic, Danielle
    Year published
    2009
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    Abstract
    The role of early to intermediate Plasmodium falciparum-induced cellular responses in the development of clinical immunity to malaria is not well understood, and such responses have been proposed to contribute to both immunity and risk of clinical malaria episodes. To investigate whether P. falciparum-induced cellular responses are able to function as predictive correlates of parasitological and clinical outcomes, we conducted a prospective cohort study of children (5 to 14 years of age) residing in a region of Papua New Guinea where malaria is endemic Live, intact P. falciparum-infected red blood cells were applied to ...
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    The role of early to intermediate Plasmodium falciparum-induced cellular responses in the development of clinical immunity to malaria is not well understood, and such responses have been proposed to contribute to both immunity and risk of clinical malaria episodes. To investigate whether P. falciparum-induced cellular responses are able to function as predictive correlates of parasitological and clinical outcomes, we conducted a prospective cohort study of children (5 to 14 years of age) residing in a region of Papua New Guinea where malaria is endemic Live, intact P. falciparum-infected red blood cells were applied to isolated peripheral blood mononuclear cells obtained at baseline. Cellular cytokine production, including production of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF) (formerly tumor necrosis factor alpha), and gamma interferon (IFN- ), was measured, and the cellular source of key cytokines was investigated. Multicytokine models revealed that increasing P. falciparum-induced IL-6 production was associated with an increased incidence of P. falciparum clinical episodes (incidence rate ratio [IRR], 1.75; 95% confidence interval [CI], 1.20 to 2.53), while increasing P. falciparum-induced TNF and IFN- production was associated with a reduced incidence of clinical episodes (IRR for TNF, 0.55 [95% CI, 0.38 to 0.80]; IRR for IFN- , 0.71 [95% CI, 0.55 to 0.90]). Furthermore, we found that monocytes/macrophages and -T cells are important for the P. falciparuminduced production of IL-6 and TNF. Early to intermediate cellular cytokine responses to P. falciparum may therefore be important correlates of immunity and risk of symptomatic malaria episodes and thus warrant detailed investigation in relation to the development and implementation of effective vaccines.
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    Journal Title
    Infection and Immunity
    Volume
    77
    Issue
    7
    DOI
    https://doi.org/10.1128/IAI.00211-09
    Copyright Statement
    © 2009 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.
    Subject
    Biological sciences
    Agricultural, veterinary and food sciences
    Biomedical and clinical sciences
    Cellular immunology
    Publication URI
    http://hdl.handle.net/10072/38168
    Collection
    • Journal articles

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