Human blood mDC subsets exhibit distinct TLR repertoire and responsiveness

Human blood DCs encompass pDCs and two subsets of mDCs: CD1c mDCs and CD141 mDCs. The rare CD141 DC population is thought to be the equivalent of mouse CD8 cDCs that play a significant role in anti-gen cross-presentation. Here, we analyzed by Q-PCR TLR1–10 expression in blood DC subsets. Whereas CD1c DCs express all TLR except TLR9, CD141 DCs present a more restricted pattern with high expression of TLR3 and-10, expression of TLR1,-2,-6, and-8, and lack of TLR4,-5,-7, and-9. The in vitro analysis of iso-lated mDC subset reponsiveness to an extensive panel of TLR ligands confirmed these results, with CD141 DCs responding only to TLR1/2,-3, and-7/8. The cyto-kine/chemokine production profile of isolated CD141 DCs was also more restricted, as they produced mainly proinflammatory cytokines but no IL-12 and to a lower level, in comparison with CD1c DCs, except for CXCL10, CCL5, and IFN-. In contrast, with the use of a whole blood assay, we found that CD141 DCs produce IL-12 in response to TLR1/2,-3, and more surprisingly,-9. Finally, both mDC subsets are potent inducers of Th1 response, particularly after TLR3 triggering. Taken together, these data confirmed functional differences between blood mDC subsets. The major response of CD141 mDCs to TLR3 ligand and their cytokine produc-tion pattern suggest a role for these cells in antiviral im-munity. J. Leukoc. Biol. 93: 000–000; 2013