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

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Title Association of early interferon-γ production with immunity to clinical malaria: a longitudinal study among Papua New Guinean children
Author D'Ombrain, Marthe C.; Robinson, Leanne J.; Stanisic, Danielle; Taraika, Jack; Bernard, Nicholas; Michon, Pascal; Mueller, Ivo; Schofield, Louis
Journal Name Clinical Infectious Diseases
Year Published 2008
Place of publication United States
Publisher Oxford University Press
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, 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.
Peer Reviewed Yes
Published Yes
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Copyright Statement Copyright 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.
Volume 47
Issue Number 11
Page from 1380
Page to 1387
ISSN 1058-4838
Date Accessioned 2011-03-22
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Cellular Immunology
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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