Role of leukocyte immunoglobulin G receptors in vaccine-induced immunity to Streptococcus pneumoniae

Members of the leukocyte immunoglobulin (Ig) G receptor (FcγR) family play a key role in antibody-mediated phagocytosis and can either enhance antigen presentation or down-modulate immune responses. We studied immune responses to a pneumococcal conjugate (pneumococcal polysaccharide serotype 1 [PPS1]-tetanus toxoid) and antibody-mediated protection in mice deficient for individual FcγRs and complement receptor 3 (CR3). FcR γ chain-deficient (FcR γ chain^-/-) mice, which lack expression of both FcγRI and III, had significantly lower anti-PPS1 IgG2b and IgG3 responses than did wild-type mice, whereas FcγRII-deficient (FcγRII^-/-) mice had significantly higher IgG2a and IgG3 titers. Wild-type and FcγRII^-/- mice were protected against infection with pneumococcal serotype 1, whereas immunized FcR γ chain^-/- and FcγRIII-deficient mice were not. Immunized CR3-deficient mice were protected against disease, and complement depletion had little effect on protection. These data indicate that activatory leukocyte FcγR, but not FcγRII (a murine homologue of human FcγRIIb), contributes to IgG-mediated protection against pneumococcal disease.