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

SummaryDendritic cells (DCs), critical antigen-presenting cells for immune control, normally derive from bone marrow precursors distinct from monocytes. It is not yet established if the large reservoir of monocytes can 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 monocytes into lymph nodes by lipopolysaccharide and live or dead gram-negative bacteria. Mobilization requires TLR4 and its CD14 coreceptor and Trif. When tested for antigen-presenting function, Mo-DCs are as active as classical DCs, including cross-presentation of proteins and live gram-negative bacteria on MHC I in vivo. Fully differentiated Mo-DCs acquire DC morphology and localize to T cell areas via L-selectin and CCR7. Thus the blood monocyte reservoir becomes the dominant presenting cell in response to select microbes, yielding DC-SIGN+ cells with critical functions of DCs.

Graphical AbstractFigure optionsDownload high-quality image (313 K)Download as PowerPoint slideHighlights
► Blood monocytes rapidly and fully differentiate to lymph node dendritic cells, Mo-DCs
► The stimulus is gram-negative bacteria or lipopolysaccharide via TLR4, CD14, and Trif
► DC-SIGN/CD209a marks Mo-DCs but is not required for them to form; CD62L and CCR7 are TLR4
► Mo-DCs are as potent as classical DCs for presenting proteins on MHC I and II