Antibody-dependent induction of type I interferons by poliovirus in human mononuclear blood cells requires the type II fcgamma receptor (CD32).
The 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-alpha-inducing capacity of attenuated poliovirus vaccine strains is dramatically enhanced in the presence of human polyvalent immunoglobulin G (IgG). The transcription of both IFN-alpha and IFN-beta 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-alpha was specifically inhibited when PBMCs were preincubated with an excess of the Fc fragment of IgG. Monoclonal antibodies directed to FcgammaRII (CD32) were also inhibitory, whereas antibodies to the two other classes of Fcgamma receptors, CD16 and CD64, were not. Also, aggregation of FcgammaRII by anti-CD32 antibodies alone failed to induce IFN-alpha 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-alpha-producing cells are able to synthesize IFN-alpha in response to poliovirus-IgG complexes.
Palmer
P
P
Laboratoire de Virologie, Hôpital Saint-Vincent-de-Paul, Université Paris V, 82 avenue Denfert-Rochereau, Paris Cedex 14, 75674, France.
Charley
B
B
Rombaut
B
B
Daëron
M
M
Lebon
P
P
D000914:Antibodies, Viral / Q000494:pharmacology*; D002213:Capsid / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D017955:Poliovirus / Q000276:immunology*; D011055:Poliovirus Vaccine, Oral / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000502:physiology; D017452:Receptors, IgG / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007370:Interferon Type I; D016898:Interferon-alpha; D011055:Poliovirus Vaccine, Oral; D012333:RNA, Messenger; D012367:RNA, Viral; D017452:Receptors, IgG; D016899:Interferon-beta