Dectin-2-Dependent NKT Cell Activation and Serotype-Specific Antibody Production in Mice Immunized with Pneumococcal Polysaccharide Vaccine

Tomomitsu Miyasaka, Yukiko Akahori, Masahiko Toyama, Namiko Miyamura, Keiko Ishii, Shinobu Saijo, Yoichiro Iwakura, Yuki Kinjo, Yoshitsugu Miyazaki, Kazunori Oishi, Kazuyoshi Kawakami

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article numbere78611
JournalPloS one
Volume8
Issue number10
DOIs
Publication statusPublished - 2013 Oct 25

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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