Publications & Reports

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

Marthe C D'Ombrain, Leanne J Robinson, Danielle I Stanisic, Jack Taraika, Nicholas Bernard, Pascal Michon, Ivo Mueller, Louis Schofield
Infection and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, University of Melbourne, Parkville, Victoria, Australia.

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 gammadelta T cells (68% of which expressed the natural killer marker CD56) and alphabeta T cells, whereas natural killer cells and other cells made only minor contributions. The expression of CD56 in malaria-responsive, IFN-gamma-expressing gammadelta 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 gammadelta T cells may contribute to protection.

Publication

  • Journal: Clinical Infectious Diseases
  • Published: 01/12/2008
  • Volume: 47
  • Issue: 11
  • Pagination: 1380-1387

Author

Health Issue