Intra-erythrocytic stages of malaria parasites can alter the surface of their host cells and release toxins which induce the production of cytokines, which in turn can up- or down-regulate the expression of adhesion receptors on the surface of microvascular endothelial cells. New adhesion receptors on endothelial cells provide the parasite with increased chances of survival despite an increasing level of host immunity. In order to take advantage of these new opportunities for survival, the parasite itself needs to make best use of its considerable ability to vary its surface antigens and adherent molecules. The paper describes the various players in this survival game and articulates a working hypothesis to explain how it may all fit together.

The ability of deproteinated malaria exoantigens from Plasmodium falciparum (Pf-MT) and P. berghei ANKA (PbA-MT) to activate murine haematopoietic cells was analysed in vitro. Malaria toxins (MT) of both plasmodium species induced cell proliferation and the production of IFN-γ in overnight and long-term (5 days) spleen and bone marrow cultures and a reduction of the number of TNF-α spot forming cells (SFC). When added to cells of malaria-experienced animals, MT decreased the number of IL-4 SPC and increased the number of IL-5 SPC. However, the same proliferative and IFN-γ induction properties as in naive cells were observed. Simultaneous addition of IL-2 and PbA-MT to spleen cells inhibited the proliferation but increased the IFN-γ production usually induced by IL-2. Flow cytometric analysis revealed that the addition of MT triggered an expansion of CD3+ and GR1+ cell populations. Our results suggest that malaria toxins of different species can induce an immediate and strong proliferation and a TH1-type cytokine release by murine cells, independently of previous in vivo priming.