Role of Dectin-2 in the serotype-specific antibody production and host protection against Streptococcus pneumoniae infection caused by pneumococcal polysaccharide vaccine (166.8)

Abstract

Abstract Anti-pneumococcal polysaccharide vaccine (PPV) induces the production of serotype-specific Ab including IgG2 in spite of its feature of thymus-independent antigen. It remains to be clarified how PPV causes a class-switching from IgM to IgG. Recently, C-type lectin receptors (CLR) sensing polysaccharides have garnered much attention in the host defense to fungal infection. In our recent study, Dectin-2, a CLR involved in the recognition of mannose-rich polysaccharides, has been found to play an important role in the host defense to pneumococcal infection. Therefore, in this study, we addressed how Dectin-2 was involved in the vaccine effect of PPV using a mouse model. The serum levels of anti-serotype 3 pneumococcal capsular polysaccharide (PPS-3) two weeks after vaccination were significantly reduced in Dectin-2 knockout (KO) mice compared to wild-type (WT) mice. Weight loss and hypothermia of mice caused by infection with Streptococcus pneumoniae (URF918) were improved in WT mice transferred with spleen cells from vaccinated WT mice compared to those from vaccinated Dectin-2KO mice. Similar tendency was observed in the survival of infected mice. In in vitro experiments, IL-12p40, TNF-α and IL-6 production by bone marrow-derived dendritic cells (BM-DCs) stimulated with PPV was abrogated in Dectin-2KO. These results suggest that Dectin-2 is involved in the PPV-induced serotype-specific Ab production and host protection through sensing the pneumococcal polysaccharide antigens.