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 mononuclear 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 extract induced a marked increase in the mononuclear cell membrane expression of functional CD95 antigen: a 3-h exposure of the mononuclear cells to anti-CD95 antibodies led to a detectable increase in the mean percentage of apoptotic nuclei found in the cultures carried out in the presence of P. falciparum extracts compared to control cultures. IL-2, IL-4, IL-6 and IL-10 promoted the viability of PBMC in cultures while IL-1alpha or IFN-gamma had no obvious impact and TNFalpha gave conflicting results. IL-2 was the most efficient cytokine at rescuing PBMC from cell death and this effect was associated 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 factors and not through their mitogenic activity. Taken together, these different observations suggested that the levels of in-vitro apoptosis observed were not only associated with parasite infection, but also potentially modulated by the human host through different pathways.
Balde
A T
AT
Laboratoire d'Immunologie; Laboratoire d'Epidémiologie, Institut Pasteur, BP 220, Dakar, Sénégal.
Aribot
G
G
Tall
A
A
Spiegel
A
A
Roussilhon
C
C
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000953:Antigens, Protozoan / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D016922:Cellular Senescence; D006801:Humans; D007378:Interleukins / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology; D012675:Senegal; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000032:analysis / Q000276:immunology
D000906:Antibodies; D000953:Antigens, Protozoan; D007378:Interleukins; D019014:fas Receptor