Human blood mDC subsets exhibit distinct TLR repertoire and responsiveness

Abstract TLR repertoire and in vitro responsiveness of blood classical DC subsets. 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 CD8α+ cDCs that play a significant role in antigen 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 isolated 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 cytokine/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-β. 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 production pattern suggest a role for these cells in antiviral immunity.