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

D&#39;Ombrain, MC; Robinson, LJ; Stanisic, DI; Taraika, J; Bernard, N; Michon, P; Mueller, I; Schofield, L

Author(s): D'Ombrain, MC; Robinson, LJ; Stanisic, DI; Taraika, J; Bernard, N; Michon, P; Mueller, I; Schofield, L;
Details: Publication Year 2008-12-01,Volume 47,Issue #11,Page 1380-1387
Journal Title: CLINICAL INFECTIOUS DISEASES
Publication Type: Journal Article
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-gamma (IFN-gamma) has been implicated in both protection against and the pathogenesis of malaria in humans. In addition, considerable heterogeneity exists among rapid IFN-gamma 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-gamma 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-gamma responses were measured, and IFN-gamma-expressing cells were characterized by flow cytometry. IFN-gamma responsiveness was then tested for associations with parasitological and clinical outcome variables. Results. Malaria-specific heterogeneity in early IFN-gamma responsiveness was observed among children. High-level early IFN-gamma responses were associated with protection from high-density and clinical P. falciparum infections. Parasite-induced early IFN-gamma was predominantly derived from gamma delta T cells (68% of which expressed the natural killer marker CD56) and alpha beta T cells, whereas natural killer cells and other cells made only minor contributions. The expression of CD56 in malaria-responsive, IFN-gamma-expressing gamma delta T cells correlated with IFN-gamma responsiveness. Conclusions. High, early IFN-gamma 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 gamma delta T cells may contribute to protection.
Publisher: OXFORD UNIV PRESS INC
Keywords: DELTA-T-CELLS; PLASMODIUM-FALCIPARUM MALARIA; NATURAL-KILLER COMPLEX; ASEXUAL BLOOD STAGES; IN-VITRO GROWTH; CEREBRAL MALARIA; AFRICAN CHILDREN; IFN-GAMMA; NK CELLS; PATHOGENESIS
Publisher's Version: https://doi.org/10.1086/592971
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-12-01 12:00:00