Pneumococcal ClpP modulates the maturation and activation of human dendritic cells: implications for pneumococcal infections.

DCs are essential for host immune response to pathogens. Pneumococcal diseases still remain to be a major global-health issue, and HSP100/ClpP is a ubiquitously present virulence determinant for Streptococcus pneumoniae. Here, we show that ClpP expression facilitates the uptake and phagocytosis of pneumococci by human DCs, and it could increase apoptosis of DCs infected with pneumococci. Furthermore, pneumococcal ClpP is required for optimal production of inflammatory cytokines and chemokines and an efficient activation of adaptive immune response in DCs. Complementary, purified rClpP protein recognizes TLR4 and functionally activates human DCs by augmenting the expression of surface molecules and the production of inflammatory cytokines and chemokines dependent on MAPKs and NF-κB signaling pathways. Besides, ClpP-treated DCs induce T cell proliferation and contribute to Th1 immune response. This study describes a novel role of ClpP in the interaction of DCs with pneumococci that could provide new insight for the progression of pneumococcal diseases and has important implications for designing pneumococcal protein vaccines.