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

D’Ombrain, Marthe C., Robinson, Leanne J., Stanisic, Danielle I., Taraika, Jack, Bernard, Nicholas, Michon, Pascal, Mueller, Ivo, and Schofield, Louis (2008) Association of early interferon‐γ production with immunity to clinical malaria: a longitudinal study among Papua New Guinean children. Clinical Infectious Diseases, 47 (11). pp. 1380-1387.

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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-γ (IFN-γ) has been implicated in both protection against and the pathogenesis of malaria in humans. In addition, considerable heterogeneity exists among rapid IFN-γ 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-γ 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-γ responses were measured, and IFN-γ–expressing cells were characterized by flow cytometry. IFN-γ responsiveness was then tested for associations with parasitological and clinical outcome variables.

Results. Malaria-specific heterogeneity in early IFN-γ responsiveness was observed among children. High-level early IFN-γ responses were associated with protection from high-density and clinical P. falciparum infections. Parasite-induced early IFN-γ was predominantly derived from γδ T cells (68% of which expressed the natural killer marker CD56) and αβ T cells, whereas natural killer cells and other cells made only minor contributions. The expression of CD56 in malaria-responsive, IFN-γ–expressing γδ T cells correlated with IFN-γ responsiveness.

Conclusions. High, early IFN-γ 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 γδ T cells may contribute to protection.

Item ID: 35851
Item Type: Article (Research - C1)
ISSN: 1537-6591
Funders: National Health and Medical Research Council (NHMRC), National Institutes of Health, Veteran's Affairs Research Service, Howard Hughes Medical Institute
Date Deposited: 31 Oct 2014 01:18
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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