A critical role of Fc receptor-mediated antibody-dependent phagocytosis in the 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 studied the mechanism of host resistance to blood-stage malaria infection using P. berghei XAT. Infection enhanced Ab-dependent phagocytosis of PRBC by splenic macrophages in wild-type C57BL/6 mice. In contrast, FcR gamma-chain knockout (FcRgamma(-/-)) mice, which lack the ability to mediate Ab-dependent phagocytosis and Ab-dependent cell-mediated cytotoxicity through FcgammaRI, FcgammaRII, and FcgammaRIII, could not induce Ab-dependent phagocytic activity. These FcRgamma(-/-) mice showed increased susceptibility 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 FcRgamma(-/-) mice could not suppress the increase in parasitemia, and almost all of these mice 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 infection, failed to induce Ab-dependent phagocytic activity and also showed reduced production of serum anti-XAT IgG2a isotype compared with control wild-type mice. These results suggest that FcR-mediated Ab-dependent phagocytosis, which is located downstream of IFN-gamma production, is important as an effector mechanism to eliminate PRBC in blood-stage P. berghei XAT infection.
Yoneto
T
T
Department of Allergology and Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Waki
S
S
Takai
T
T
Tagawa Yi
Iwakura
Y
Y
Mizuguchi
J
J
Nariuchi
H
H
Yoshimoto
T
T
D000818:Animals; D000913:Antibodies, Protozoan / Q000008:administration & dosage; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics / Q000276:immunology*; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate / Q000235:genetics; D007116:Immunization, Passive / Q000379:methods; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000096:biosynthesis / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000097:blood; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000469:parasitology; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000469:parasitology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D010962:Plasmodium berghei / Q000254:growth & development* / Q000276:immunology*; D011961:Receptors, Fc / Q000502:physiology*; D013154:Spleen / Q000276:immunology / Q000469:parasitology
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D011961:Receptors, Fc; D007371:Interferon-gamma