Cellular basis of early cytokine response to Plasmodium falciparum.
Uncertainty remains about the cellular origins of the earliest phase of the proinflammatory cytokine response to malaria. Here we show by fluorescence-activated cell sorter analysis that gammadelta T cells and CD14+ cells from nonimmune donors produce tumor necrosis factor and that gammadelta T cells also produce gamma interferon within 18 h of contact with mycoplasma-free Plasmodium falciparum-infected erythrocytes in vitro. This early cytokine response is more effectively induced by intact than by lysed parasitized erythrocytes. However, the IFN-gamma response to lysed parasites is considerably enhanced several days after peripheral blood mononuclear cells are primed with low numbers of intact parasitized erythrocytes, and in this case it derives from both alphabeta and gammadelta T cells. These data show that naïve gammadelta T cells can respond very rapidly to malaria infection but that malaria fever may involve a multistage process in which the priming of both gammadelta and alphabeta T-cell populations boosts the cytokine response to lysed parasite products released at schizont rupture.
Department of Paediatrics, Oxford University, Oxford OX3 9DU, United Kingdom.
M
M
Hensmann
D
D
Kwiatkowski
D000328:Adult; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D010963:Plasmodium falciparum / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma