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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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-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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