Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209 + dendritic cells for immune T cell areas

Dendritic 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. �� 2010 Elsevier Inc.We thank members of the Steinman lab for valuable discussion, J. Adams for graphics, A.J. North and S.A. Galdeen for DIC imaging at the bioimaging resource center, S. Mazel and C. Bare for flow cytometry at the resource center of Rockefeller University, Y. Oh and I. Jang for CSP preparation, J.D. Schauer for mAb purification, J. Gonzalez for ELISA assays (Rockefeller University Center for Clinical and Translational Science, UL1RR024143 from National Center for Research Resource). We thank the Consortium for Functional Glycomics supported by NIGMS (GM62116) for DC-SIGN/CD209a ���/��� mice. We were supported by grants from the NIH (AI40045 and AI40874), the Bill and Melinda Gates Foundation (R.M.S.), New York Community Trust's Francis Florio funds for blood diseases (C.C.), and a Funda����o para a Ci��ncia e Tecnologia PhD scholarship (I.M. SFRH/BD/41073/2007)