A critical role of Fc receptor-mediated antibody-dependent phagocytosis inthe host resistance to blood-stage Plasmodium berghei XAT infection

Plasmodium berghei XAT is an irradiation-induced attenuated variant derived from the lethal strain P. berghei NK65, and its blood-stage parasites are spontaneously cleared in immune competent mice. In the present study, we st udied the mechanism of host resistance to blood-stage malaria infection usi ng P. berghei XAT. Infection enhanced Ab-dependent phagocytosis of PRBC by splenic macrophages in wild-type C57BL/6 mice. In contrast, FcR gamma -chai n knockout (FcR gamma (-/-)) mice, which lack the ability to mediate Ab-dep endent phagocytosis and Ab-dependent cell-mediated cytotoxicity through Fc gamma RI, Fc gamma RII, and Fc gamma RIII, could not induce Ab-dependent ph agocytic activity. These FeR gamma (-/-) mice showed increased susceptibili ty to the P. berghei XAT infection, with eventually fatal results, although they produced comparable amounts of IFN-gamma by spleen cells and anti-XAT Abs in serum. In addition, passive transfer of anti-XAT IgG obtained from wild-type mice that had recovered from infection into FcR gamma (-/-) mice could not suppress the increase in parasitemia, and almost all of these mic e died after marked parasitemia. In contrast, passive transfer of anti-XAT IgG into control wild-type mice inhibited the increase in parasitemia. IFN- gamma (-/-) mice, which were highly susceptible to the P. berghei XAT infec tion, failed to induce Ab-dependent phagocytic activity and also showed red uced production of serum anti-XAT IgG2a isotype compared with control wild- type mice. These results suggest that FcR-mediated Ab-dependent phagocytosi s, which is located downstream of IFN-gamma production, is important as an effector mechanism to eliminate PRBC in blood-stage P. berghei XAT infectio n.