PLASMODIUM-FALCIPARUM INDUCES APOPTOSIS IN HUMAN MONONUCLEAR-CELLS

The level of spontaneous apoptosis in short-term lymphocyte cultures w as evaluated in different human immunodeficiency virus-negative groups of either healthy control individuals or patients with clinical malar ia. The mean percentage of spontaneous apoptosis found in patients dur ing a malaria attack was significantly higher than in sex- and age-mat ched healthy controls. The healthy asymptomatic controls were individu als with different degrees of exposure to Plasmodium falciparum as ref lected by their various mean levels of specific anti-P. falciparum (im munoglobulin G and M) antibodies. The percentages of apoptotic nuclei were found to be significantly higher in lymphocytes from subjects liv ing in an area where malaria is holoendemic than in lymphocytes from s ubjects less exposed. Concentrations of soluble plasma interleukin-2 r eceptor were also higher in subjects from areas where malaria is endem ic than in other groups, revealing different levels of lymphocyte acti vation. Of particular relevance to the in vivo situation, a P. falcipa rum schizont-rich extract induced a systematic and significant elevati on of apoptotic nuclei at day 6 in 87.5% (35 of 40) of the subjects te sted. in additional studies with different concentrations of extract, [H-3]thymidine incorporation was concomitant with a low or limited lev el of apoptosis. Taken together, our results strongly suggest that acu te as well as chronic asymptomatic P. falciparum infections were consi stently associated with a marked increase in the level of mononuclear cell apoptosis. This process could be implicated in some of the altera tions reported for the proliferative T-cell responses in areas where m alaria is endemic.