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Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients.

TitlePlasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients.
Publication TypeJournal Article
Year of Publication2007
AuthorsDecalf J, Fernandes S, Longman R, Ahloulay M, Audat F, Lefrerre F, Rice CM, Pol S, Albert ML
JournalJ Exp Med
Volume204
Issue10
Pagination2423-37
Date Published2007 Oct 1
ISSN0022-1007
KeywordsAutocrine Communication, Cell Differentiation, Cells, Cultured, Cytokines, Dendritic Cells, Hepacivirus, Hepatitis C, Chronic, Humans, Immune Tolerance, Inflammation, Toll-Like Receptors, Virus Replication
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.

DOI10.1084/jem.20070814
Alternate JournalJ. Exp. Med.
PubMed ID17893202
PubMed Central IDPMC2118448