title: Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients.
abstract: Plasmacytoid dendritic cells (pDCs) are the professional type I interferon (IFN)-producing cells, and upon activation they traffic to lymph organs, where they bridge innate and adaptive immunity. Using multianalyte profiling (MAP), we have mapped the key chemokines and cytokines produced in response to pDC activation, taking into consideration the role of autocrine IFN, as well as paracrine effects on other innate cells (e.g., monocytes and conventional DCs). Interestingly, we identify four distinct cytokine/chemokine loops initiated by Toll-like receptor engagement. Finally, we applied this analytic approach to the study of pDC activity in chronic hepatitis C patients. Based on the activation state of pDCs in fresh blood, the lack of agonistic activity of infectious virions, the production of a broad array of cytokines/chemokines once stimulated, and the direct effects of pDCs on other PBMCs, we conclude that the pDCs from hepatitis C virus (HCV)-infected individuals are fully functional and are, indeed, a viable drug target. In sum, this study provides insight into the use of MAP technology for characterizing cytokine networks, and highlights how a rare cell type integrates the activation of other inflammatory cells. Furthermore, this work will help evaluate the therapeutic application of pDC agonists in diseases such as chronic HCV infection.
authors: The Laboratory of Dendritic Cell Biology, Department of Immunology, Institut Pasteur, 75724 Paris, Cedex 15, France.
authors: Jérémie
authors: J
authors: Decalf
authors: Sandrine
authors: S
authors: Fernandes
authors: Randy
authors: R
authors: Longman
authors: Mina
authors: M
authors: Ahloulay
authors: Françoise
authors: F
authors: Audat
authors: François
authors: F
authors: Lefrerre
authors: Charles M
authors: CM
authors: Rice
authors: Stanislas
authors: S
authors: Pol
authors: Matthew L
authors: ML
authors: Albert
mesh_terms: D019898:Autocrine Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000378:metabolism; D014779:Virus Replication
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors