Quantification of human peripheral blood NK subsets has been made in a group of Kenyan adults and children with acute P. falciparum malaria. Results were compared with data obtained from three age- and sex-matched control cohorts: parasitaemic but asymptomatic children; aparasitaemic children and adults; and adult Caucasians with no previous history of malaria. Separated NK subsets were tested in vitro for cytotoxicity to erythrocytic schizonts of P. falciparum in the presence and absence of cytokines. There was a statistically significant quantitative and qualitative depression of the CD3-CD56+ subset in patients with acute malaria and this was accompanied by an expansion of the 'non-functional' CD3-CD57+CD16-CD56- subset. Both CD3-CD16+ and CD3-CD56+ NK cells from all patients and donors lysed schizonts, and this cytotoxicity was enhanced by the addition of recombinant interferon-alpha and/or IL-2, notably with the CD3-CD56+ subset. Interestingly, asymptomatic donors had the highest levels of CD3-CD56+ NK cells, which also demonstrated an enhanced response to cytokine stimulation. Cytotoxicity to schizonts was accompanied by the release of soluble NK cell lytic factors. Neomycin suppressed cytotoxicity in a dose-dependent manner, indicating that the lysis of schizonts by NK cells involves phospholipase C-mediated phosphoinositide metabolism. Our findings define a role for NK cells in immunity to malaria through the lysis of infected erythrocytes as a first-line defence against the parasite.
Human erythrocytes with a deficiency in glycophorin A (En(a-) cells) and glycophorin B (S-s-U- and S-s-U+ cells) show significant resistance in vitro to invasion by Plasmodium falciparum merozoites. Treatment of normal erythrocytes with trypsin and chymotrypsin also reduced invasion. Trypsinization of S-s- and En(a-) red cells, a process which removes the T1 peptide of glycophorins A and C, produced cells almost refractory to invasion. The human K562 erythroleukaemia cell line, which also expresses glycophorin A, was not invaded and possible explanations for this result are discussed. It is suggested that determinants carried on the red cell sialoglycoproteins (glycophorins A, B and C), in particular the T1 peptide of glycophorins A and C, play an essential role in attachment and invasion by P. falciparum merozoites. The oligosaccharide components found on this peptide may play a role in the initial binding between red cell and merozoites.
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