The course of a primary infection of Plasmodium yoelii 17XL in both 129S1 and IFN-γ receptor-deficient mice.

In the present study, we found that 129S1 mice are resistant to the infection with Plasmodium yoelii 17XL, which is highly virulent and causes lethal infection in various strains of mice. In contrast, IFN-γ receptor-deficient (IFN-γR(-/-)) mice on the 129S1 background were much more susceptible than 129S1 mice with intraperitoneal infection with 1 × 10(5) parasitized erythrocytes. The mortality in 129S1 and IFN-γR(-/-) mice was 11.6 and 79.4 %, respectively. Following inoculation of the parasites, both 129S1 and IFN-γR(-/-) mice showed a progressive increase in parasitemia. Growth rate of malaria parasites at the early stages of infection in the IFN-γR(-/-) mice was faster than that in 129S1 mice, and this difference in growth rate might cause the earlier death of IFN-γR(-/-) host from day 8 of infection than that of 129S1. In surviving mice of both strains, however, malaria parasites in their bloodstream began to decrease in number right after a peak of parasitemia and were not detectable by a microscopic examination during the observation period. Next, we investigated the cytokine and antibody production in 129S1 and IFN-γR(-/-) mice during infection. An analysis of cytokines showed that serum IFN-γ and IL-4 levels elevated significantly from day 1 and day 4 of infection, respectively, in both 129S1 and IFN-γR(-/-) mice when compared with the levels from the uninfected controls. Following the infection, significantly higher levels of malaria-specific IgG1 and IgG2a antibodies in the infected 129S1 mice were detected from day 15, and these elevations were coincident with the decrease of parasitemia. On the other hand, the levels of malaria-specific antibodies in IFN-γR(-/-) mice had a tendency to elevate on day 21 but did not reach statistical significance. The present data indicate that IFN-γR plays an essential role in mediating the early immune mechanisms induced by the infection of erythrocytic stages of P. yoelii 17XL parasite, leading to host survival.