Circulating concentrations of soluble granzyme A and B increase during natural and experimental Plasmodium falciparum infections

Release of soluble Granzymes (sGranzymes) is considered to reflect activation of cytotoxic T lymphocytes and NK cells. sGranzymes and a number of pro-inflammatory cytokines were measured in plasma of malaria patients with natural or experimentally induced Plasmodium falciparum infections. Concentrations of sGranzyme A and B, IL-10, IL-12p70 and CRP were significantly increased in African children presenting with clinical malaria; IL-10 and CRP concentrations were significantly correlated with disease severity. In nonimmune Dutch volunteers which were experimentally infected by P falciparum-infected mosquitoes, sGranzyme A increment started 1-2 days prior to clinical symptoms and microscopically detectable parasitaemia. This coincided with increases in IFNgamma IL-12p40 and IL-8, while sGranzyme B and IL-10 levels increased 24-48 h later. The elevation of sGranzyme A and IFNgamma in nonimmune volunteers suggests that NK cells are activated upon release of parasites by infected liver cells and subsequently during blood stage infection; thus, NK cells are likely involved innate immune human host resistance in the early phase of a malaria infection.