title: Human blood mDC subsets exhibit distinct TLR repertoire and responsiveness.
abstract: 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.
authors: Nantes CHU, Quai Moncousu, Nantes, France. caroline.hemont@chu-nantes.fr
authors: Caroline
authors: C
authors: Hémont
authors: Antoine
authors: A
authors: Neel
authors: Michèle
authors: M
authors: Heslan
authors: Cécile
authors: C
authors: Braudeau
authors: Régis
authors: R
authors: Josien
mesh_terms: D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000145:classification / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D018949:Antigens, CD1; C437944:CD1C protein, human; D016207:Cytokines; D006023:Glycoproteins; D020033:Protein Isoforms; D051193:Toll-Like Receptors