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.
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: Yoram Vodovotz; Gregory Constantine; James Faeder; Qi Mi; Jonathan Rubin; John Bartels; Joydeep Sarkar; Robert H Squires; David O Okonkwo; Jörg Gerlach; Ruben Zamora; Shirley Luckhart; Bard Ermentrout; Gary An Journal: Immunopharmacol Immunotoxicol Date: 2010-06 Impact factor: 2.730
Authors: Collins Ouma; Gregory C Davenport; Steven Garcia; Prakasha Kempaiah; Ateefa Chaudhary; Tom Were; Samuel B Anyona; Evans Raballah; Stephen N Konah; James B Hittner; John M Vulule; John M Ong'echa; Douglas J Perkins Journal: Hum Genet Date: 2011-08-05 Impact factor: 4.132
Authors: Simon Metenou; Benoit Dembélé; Siaka Konate; Housseini Dolo; Siaka Y Coulibaly; Yaya I Coulibaly; Abdallah A Diallo; Lamine Soumaoro; Michel E Coulibaly; Dramane Sanogo; Salif S Doumbia; Marissa Wagner; Sekou F Traoré; Amy Klion; Siddhartha Mahanty; Thomas B Nutman Journal: J Immunol Date: 2009-06-26 Impact factor: 5.422
Authors: Bruno B Andrade; Antonio Reis-Filho; Sebastião M Souza-Neto; Jorge Clarêncio; Luis M A Camargo; Aldina Barral; Manoel Barral-Netto Journal: Malar J Date: 2010-01-13 Impact factor: 2.979