Role of Dectin-2 in the host defense against Streptococcus pneumoniae infection (45.8)

Abstract

Abstract Streptococcus pneumoniae possesses a thick polysaccharide capsule. Host defense to this bacterium is mediated by neutrophilic inflammatory responses, which is critically regulated by innate immune mechanism. S. pneumoniae has been reported to be sensed by pattern-recognition receptors such as TLR2, TLR4 and SIGN-R1. In this study, we examined the role of Dectin-2 in the host defense to S. pneumoniae infection. When bone marrow-derived dendritic cells from wild-type (WT) and Dectin-2KO mice were stimulated with culture supernatants (Sup) of a strain of S. pneumoniae (URF918) or its ConA-bound fraction, IL-12p40 production was abrogated in Dectin-2KO mice. In a NFAT-GFP reporter assay, Sup provided a positive signal in Dectin-2 gene-transfected reporter cells. These results suggest that Dectin-2 senses mannose-containing polysaccharides in S. pneumoniae capsule. Dectin-2KO mice infected intratracheally with S. pneumoniae showed shorter survival and larger bacterial burden and lower IFN-γ production in lungs than WT mice. Although the neutrophilic infiltration in lungs was equivalent in both mice, the ratio of engulfed/un-engulfed neutrophils was lower in KO mice than in WT mice. The levels of anti-pneumococcal polysaccharide Ab in bronchoalveolar lavage fluid and serum were lower in KO mice than WT mice. These results suggest that Dectin-2 plays critical roles in the host defense to S. pneumoniae infection through promoting the Ab-mediated phagocytosis by neutrophils.