Apoptosis modulation in mononuclear cells recovered from individuals exposed to Plasmodium falciparum infection

In endemic areas asymptomatic infection by the malaria parasite Plasmodium falciparum was found associated with elevated percentages of human host's m ononuclear cell spontaneous in-vitro apoptosis. In Dielmo, a village where malaria is holoendemic, apoptosis was age-and parasite-dependent. In-vitro exposure of peripheral blood mononuclear cells (PBMC) to the parasite extra ct induced a marked increase in the mononuclear cell membrane expression of functional CD95 antigen: a 3-h exposure of the mononuclear cells to anti-C D95 antibodies led to a detectable increase in the mean percentage of apopt otic nuclei found in the cultures carried out in the presence of P. falcipa rum extracts compared to control cultures. IL-2, IL-4, IL-6 and IL-10 promo ted the viability of PBMC in cultures while IL-1 alpha or IFN-gamma had no obvious impact and TNF alpha gave conflicting results. IL-2 was the most ef ficient cytokine at rescuing PBMC from cell death and this effect was assoc iated with a strong increase in T cell activation. in contrast IL-4 and IL- 10 had no such effect on T cell activation hence they acted as survival fac tors and not through their mitogenic activity. Taken together, these differ ent observations suggested that the levels of in-vitro apoptosis observed w ere not only associated with parasite infection, but also potentially modul ated by the human host through different pathways.