Complement contributes to protective immunity against reinfection by Plasmodium chabaudi chabaudi parasites

We have studied the impact of deficiency of the complement system on the pr ogression and control of the erythrocyte stages of the malarial parasite Pl asmodium chabaudi chabaudi. Clq-deficient mice and factor B- and C2-deficie nt mice, deficient in the classical complement pathway and in both the alte rnative and classical complement activation pathways, respectively, exhibit ed only a slight delay in the resolution of the acute phase of parasitemia. Complement-deficient mice showed a transiently elevated level of gamma int erferon (IFN-gamma) in the plasma at the time of the acute parasitemia comp ared with that of wild-type mice. Although there was a trend for increased precursor frequencies in CD4(+) T cells from Clq-deficient mice producing I FN-gamma in response to malarial antigens in vitro, intracellular cytokine staining of spleen cells ex vivo showed no difference in the numbers of IFN -gamma (+) splenic CD4(+) and CD8(+) cells. In contrast, Clq deficient anim als mere significantly more susceptible to a second challenge with the same parasite. Clq-deficient animals showed a reduced level of anti-malarial im munoglobulin G2a (IgG2a) antibody 100 days after primary infection. However , following a significantly higher parasitemia, Clq-deficient mice had incr eased levels of IgM and IgG2a anti-malarial antibodies. In summary, this st udy indicates that while complement plays only a minor role in the control of the acute phase of parasitemia of a primary infection, it does contribut e to parasite control in reinfection.