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

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.

• 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.)

Chemical References

• Interferon-gamma

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)