title: Human plasmacytoid dendritic cells are unresponsive to bacterial stimulation and require a novel type of cooperation with myeloid dendritic cells for maturation.
abstract: Dendritic cell (DC) populations play unique and essential roles in the detection of pathogens, but information on how different DC types work together is limited. In this study, 2 major DC populations of human blood, myeloid (mDCs) and plasmacytoid (pDCs), were cultured alone or together in the presence of pathogens or their products. We show that pDCs do not respond to whole bacteria when cultured alone, but mature in the presence of mDCs. Using purified stimuli, we dissect this cross-talk and demonstrate that mDCs and pDCs activate each other in response to specific induction of only one of the cell types. When stimuli for one or both populations are limited, they synergize to reach optimal activation. The cross-talk is limited to enhanced antigen presentation by the nonresponsive population with no detectable changes in the quantity and range of cytokines produced. We propose that each population can be a follower or leader in immune responses against pathogen infections, depending on their ability to respond to infectious agents. In addition, our results indicate that pDCs play a secondary role to induce immunity against human bacterial infections, which has implications for more efficient targeting of DC populations with improved vaccines and therapeutics.
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, Siena, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Piccioli
authors.forename: Chiara
authors.initials: C
authors.lastname: Sammicheli
authors.forename: Simona
authors.initials: S
authors.lastname: Tavarini
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Frigimelica
authors.forename: Andrea G O
authors.initials: AG
authors.lastname: Manetti
authors.forename: Annalisa
authors.initials: A
authors.lastname: Nuccitelli
authors.forename: Susanna
authors.initials: S
authors.lastname: Aprea
authors.forename: Sara
authors.initials: S
authors.lastname: Valentini
authors.forename: Erica
authors.initials: E
authors.lastname: Borgogni
authors.forename: Andreas
authors.initials: A
authors.lastname: Wack
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Valiante
mesh_terms: D001419:Bacteria / Q000472:pathogenicity*; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D005434:Flow Cytometry; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology* / Q000382:microbiology*; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics; D014162:Transfection
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D008156:Luciferases