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 gamma delta T cells and CD14(+) cells from nonimmune donors produce tumor necrosis factor and that gamma delta 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 alpha beta and gamma delta T cells. These data show that naive gamma delta T cells can respond very rapidly to malaria infection but that malaria fever may involve a multistage process in which the priming of both gamma delta and alpha beta T-cell populations boosts the cytokine response to lysed parasite products released at schizont rupture.