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

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

doi:10.1371/journal.pone.0078611

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.

Highlights

Streptococcus pneumoniae is a leading causative bacterium of community-acquired pneumonia [1,2,3]
We found that Dectin-2 was absolutely required for the production of IL-12p40 by dendritic cells upon in-vitro stimulation with pneumococcal polysaccharide vaccine (PPV), and that immunization with PPV caused IFN-c synthesis by natural killer T (NKT) cells, which was possibly activated by the secretion of IL-12 from DCs leading to the production of serotype-specific Ab
To assess the role of Dectin-2 in the Ab production caused by PPV immunization, WT and Dectin-2KO mice were injected with PPV, and the serum levels of anti-pneumococcal polysaccharide type 3 (PPS3) IgM, IgG and IgG3 were measured on day 14

Summary

Introduction

Streptococcus pneumoniae is a leading causative bacterium of community-acquired pneumonia [1,2,3]. Immunization with 23-valent pneumococcal polysaccharide vaccine (PPV) results in a protective IgG response in vaccinated individuals who have a high risk of pneumococcal infection [6,7,8]. IgG production against pneumococcal polysaccharides is a key factor in protecting hosts from pneumococcal infection. It remains to be clarified how PPV causes the production of IgG. C-type lectin receptors (CLRs), pattern recognition receptors (PRRs) for pathogen-derived polysaccharides, have garnered much attention from many investigators with respect to their role in host defense against fungal infection [9]. The triggering of Dectin-2mediated stimulation by fungal hyphae or specific Ab leads to the activation of NF-kB and the production of proinflammatory cytokines [12,13]

Methods

Results

Conclusion