Details

Autor(en) / Beteiligte

• D'Ombrain, Marthe C.
• Robinson, Leanne J.
• Stanisic, Danielle I.
• Taraika, Jack
• Bernard, Nicholas
• Michon, Pascal
• Mueller, Ivo
• Schofield, Louis

Titel

Association of Early Interferon-γ Production with Immunity to Clinical Malaria: A Longitudinal Study among Papua New Guinean Children

Ist Teil von

• Clinical infectious diseases, 2008-12, Vol.47 (11), p.1380-1387

Ort / Verlag

Oxford: The University of Chicago Press

Erscheinungsjahr

2008

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• 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.