Antibody-Dependent Induction of Type I Interferons by Poliovirus in Human Mononuclear Blood Cells Requires the Type II Fcγ Receptor (CD32)

AbstractThe induction of type I interferons (IFNs) in peripheral blood mononuclear cells (PBMCs) can be triggered by viral infection or exposure to viral glycoproteins. Here we show that the IFN-α-inducing capacity of attenuated poliovirus vaccine strains is dramatically enhanced in the presence of human polyvalent immunoglobulin G (IgG). The transcription of both IFN-α and IFN-β genes was detected by RT-PCR in stimulated cells. This antibody-dependent activation of type I IFNs genes was also observed with Formalin-inactivated or UV-inactivated poliovirus, but not with empty poliovirus capsids. The ability of poliovirus–antibody complexes to induce IFN-α was specifically inhibited when PBMCs were preincubated with an excess of the Fc fragment of IgG. Monoclonal antibodies directed to FcγRII (CD32) were also inhibitory, whereas antibodies to the two other classes of Fcγ receptors, CD16 and CD64, were not. Also, aggregation of FcγRII by anti-CD32 antibodies alone failed to induce IFN-α production. Our results suggest that induction of type I interferons by poliovirus–antibody complexes depends on CD32-mediated phagocytosis of RNA-containing viral particles. As suggested by the results of an ELISPOT analysis, only a fraction of the IFN-α-producing cells are able to synthesize IFN-α in response to poliovirus–IgG complexes