The inhibition ofPlasmodium falciparumgrowthin vitroby sera from mice infected with malaria or treated with TNF

Abstract

SUMMARYDespite some years of enquiry, the mechanism that leads to intra-erythrocytic death of malarial parasites during the host's response to infection has not been elucidated. We report here that serum from mice undergoing a successful immune response toPlasmodium chabaudidoes not inhibitPlasmodium falciparumunless thePl. chabaudiis virulent enough to rise to at least 50% parasitaemia and to cause illness. This appears to be true of the 556 KA and DS strains ofPl chabaudi, and also other murine malaria parasites. In mice infected withPl. chabaudi556 KA inhibitory activity coincided with the presence of TNF in their serum. Exogenous TNF generated inhibitory activity in the serum of mice only if the animals were pretreated withProprionobacterium acnes, implying a role for activated macrophages downstream from TNF in this process. The difference in inhibitory activity againstPl. falciparumin serum from mice infected withPl. chabaudiof more or less virulence may be one of degree. Alternatively two distinct mechanisms may operate, the second coming into operation only in ill mice, with higher parasite burdens.