BDCA1-Positive Dendritic Cells (DCs) Represent a Unique Human Myeloid DC Subset That Induces Innate and Adaptive Immune Responses to Staphylococcus aureus Infection

Abstract

ABSTRACTStaphylococcus aureusbloodstream infection (bacteremia) is a major cause of morbidity and mortality and places substantial cost burdens on health care systems. The role of peripheral blood dendritic cells (PBDCs) in the immune responses againstS. aureusinfection has not been well characterized. In this study, we demonstrated that BDCA1+myeloid DCs (mDCs) represent a unique PBDC subset that can induce immune responses againstS. aureusinfection. BDCA1+mDCs could engulfS. aureusand strongly upregulated the expression of costimulatory molecules and production of proinflammatory cytokines. Furthermore, BDCA1+mDCs expressed high levels of major histocompatibility complex (MHC) class I and II molecules in response toS. aureusand greatly promoted proliferation and gamma interferon (IFN-γ) production in CD4 and CD8 T cells. Moreover, BDCA1+mDCs expressed higher levels of Toll-like receptor 2 (TLR-2) and scavenger receptor A (SR-A) than those on CD16+and BDCA3+mDCs, and these two receptors were both required for the recognition ofS. aureusand the subsequent activation of BDCA1+mDCs. Finally, BDCA1+mDC-mediated immune responses againstS. aureuswere dependent on MyD88 signaling pathways. These results demonstrate that human BDCA1+mDCs represent a unique subset of mDCs that can respond toS. aureusto undergo maturation and activation and to induce Th1 and Tc1 immune responses.