Fc receptors are not required for antibody-mediated protection against lethal malaria challenge in a mouse model.
The mechanisms by which Abs mediate protection during blood-stage malaria infections is controversial, with some evidence pointing to the direct effect of Abs on parasite invasion and growth, while other studies suggest that Abs act in cooperation with monocytes to achieve parasite inhibition. To determine whether the effector phase of protection in vivo to the rodent parasite Plasmodium yoelii yoelii requires Fc receptor bearing cells, we passively transferred immune sera into FcR gamma-chain knockout mice. Inflammatory macrophages from these knockout mice were unable to mediate phagocytosis or Ab-dependent cell-mediated cytotoxicity (ADCC) through Fc gamma RI, Fc gamma RII, or Fc gamma RIII. Passive transfer of either P. y. yoelii hyperimmune sera or anti-GST-PYC2 sera directed to the major merozoite surface protein (MSP-1) of this parasite enabled both BALB/cByJ mice and FcR gamma-chain-deficient mice to resist lethal P. y. yoelii 17XL (Py17XL) challenge. mAb302, a protective IgG3 Ab, also passively protected both strains of mice. Most of these samples contain Ab isotypes that would not be able to protect mice if their protective effects required Ab-dependent cell-mediated cytotoxicity. These results establish that, in this infection, protection is directly mediated by Abs and does not require the participation of Fc receptors.
Department of Microbiology and Immunology, Allegheny University of the Health Sciences, Philadelphia, PA 19129, USA.
H L
HL
Rotman
T M
TM
Daly
R
R
Clynes
C A
CA
Long
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000502:physiology*; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology; D007106:Immune Sera / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D008288:Malaria / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity; D017452:Receptors, IgG / Q000097:blood / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007106:Immune Sera; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D017780:Malaria Vaccines; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase