Microbial Stimulation Fully Differentiates Monocytes to DC-SIGN/CD209+ Dendritic Cells for Immune T Cell Areas

Summary Dendritic cells (DCs), critical antigen-presenting cellsfor immune control, normally derive from bone marrow precursors distinct from monocytes. It is not yet established if the large reservoir of monocytescan develop into cells with critical features of DCs in vivo. We now show that fully differentiated monocyte-derived DCs (Mo-DCs) develop in mice and DC-SIGN/CD209a marks the cells. Mo-DCs are recruited from blood monocytesinto lymph nodes by lipopolysaccharide and live or dead gram-negative bacteria. Mobilization requires TLR4 and its CD14coreceptor and Trif. When tested for antigen-presentingfunction, Mo-DCs are as active as classical DCs, including cross-presentationof proteins and live gram-negative bacteriaon MHC I in vivo. Fully differentiated Mo-DCs acquire DC morphology and localize to T cell areas via L-selectinand CCR7. Thus the blood monocytereservoir becomes the dominant presenting cell in response to select microbes, yielding DC-SIGN+ cells with critical functions of DCs.