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.
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Authors | Marthe C D'Ombrain, Leanne J Robinson, Danielle I Stanisic, Jack Taraika, Nicholas Bernard, Pascal Michon, Ivo Mueller, Louis Schofield |
Journal | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
(Clin Infect Dis)
Vol. 47
Issue 11
Pg. 1380-7
(Dec 01 2008)
ISSN: 1537-6591 [Electronic] United States |
PMID | 18947328
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
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Topics |
- Adolescent
- Animals
- Cells, Cultured
- Child
- Child, Preschool
- Flow Cytometry
- Humans
- Interferon-gamma
(immunology)
- Killer Cells, Natural
(immunology)
- Leukocytes, Mononuclear
(immunology)
- Longitudinal Studies
- Malaria, Falciparum
(immunology, parasitology, physiopathology)
- Papua New Guinea
- Plasmodium falciparum
(immunology)
- Statistics as Topic
- T-Lymphocyte Subsets
(immunology)
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