title: Dectin-2-dependent NKT cell activation and serotype-specific antibody production in mice immunized with pneumococcal polysaccharide vaccine.
abstract: Although thymus-independent type 2 antigens generally do not undergo Ig class switching from IgM to IgG, pneumococcal polysaccharide vaccine (PPV) induces the production of serotype-specific IgG. How this happens remains unclear, however. In the present study, PPV immunization induced production of IgG as well as IgM specific for a serotype 3-pneumococcal polysaccharide in the sera of wild-type (WT) mice, but this phenomenon was significantly reduced in Dectin-2 knockout (KO) mice. Immunization with PPV caused IL-12p40 production in WT mice, but this response was significantly reduced in Dectin-2KO mice. Likewise, immunization with PPV activated natural killer T (NKT) cells in WT mice but not in Dectin-2KO mice. Furthermore, administration of α-galactosylceramide, recombinant (r)IL-12 or rIFN-γ improved the reduced IgG levels in Dectin-2KO mice, and treatment with neutralizing anti-IFN-γ mAb resulted in the reduction of IgG synthesis in PPV-immunized WT mice. Transfer of spleen cells from PPV-immunized WT mice conferred protection against pneumococcal infection on recipient mice, whereas this effect was cancelled when the transferred spleen cells were harvested from PPV-immunized Dectin-2KO mice. These results suggest that the detection of PPV antigens via Dectin-2 triggers IL-12 production, which induces IFN-γ synthesis by NKT cells and subsequently the production of serotype-specific IgG.
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyasaka
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Akahori
authors.forename: Masahiko
authors.initials: M
authors.lastname: Toyama
authors.forename: Namiko
authors.initials: N
authors.lastname: Miyamura
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kinjo
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D001854:Bone Marrow Cells / Q000166:cytology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D005260:Female; D055786:Gene Knockout Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013045:Species Specificity; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D053762:Interleukin-12 Subunit p40; D037181:Lectins, C-Type; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial; C445340:dectin-2, mouse; D007371:Interferon-gamma