Dendritic cells orchestrate innate and adaptive immune responses, which are central to establishing efficient responses to vaccination. Wall-associated protein A (WapA) of Streptococcus mutans was previously used as a vaccine in animal studies for immunization against dental caries. However, as a cell surface protein, whether WapA activates innate immune responses and the effects of WapA on DCs remain unclear. In this study, WapA was cloned into the GST fusion vector pEBG, which can be expressed efficiently in mammalian cells. We found that when added before stimulation with LPS, purified WapA-GST protein increased TLR4-induced NF-κB and MAPK signalling pathway activation. Pretreatment with WapA-GST also increased LPS-induced proinflammatory cytokine production by DCs, including IL-12, IL-6 and TNF-α. Furthermore, expression of the DC maturation markers CD80/86, CD40 and MHC II was also increased by WapA pretreatment. These data indicate that WapA is recognized by DCs and promotes DC maturation.