Journal article

Molecular dissection of plasmacytoid dendritic cell activation in vivo during a viral infection

Elena Tomasello, Karima Naciri, Rabie Chelbi, Gilles Bessou, Anissa Fries, Elise Gressier, Abdenour Abbas, Emeline Pollet, Philippe Pierre, Toby Lawrence, Vu Manh Thien-Phong, Marc Dalod

The EMBO Journal | WILEY | Published : 2018

Abstract

Plasmacytoid dendritic cells (pDC) are the major source of type I interferons (IFN-I) during viral infections, in response to triggering of endosomal Toll-like receptors (TLRs) 7 or 9 by viral single-stranded RNA or unmethylated CpG DNA, respectively. Synthetic ligands have been used to disentangle the underlying signaling pathways. The adaptor protein AP3 is necessary to transport molecular complexes of TLRs, synthetic CpG DNA, and MyD88 into endosomal compartments allowing interferon regulatory factor 7 (IRF7) recruitment whose phosphorylation then initiates IFN-I production. High basal expression of IRF7 by pDC and its further enhancement by positive IFN-I feedback signaling appear to be ..

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University of Melbourne Researchers

Grants

Awarded by Agence Nationale de la Recherche


Awarded by European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013 Grant, "SystemsDendritic")


Awarded by Fondation pour la Recherche Medicale (FRM)


Awarded by Agence Nationale de la Recherche (ANR) (SCAPIN)


Awarded by DCBIOL Labex


Awarded by A*MIDEX project - French Government's "Investissements d'Avenir" program


Funding Acknowledgements

We thank all the staff of the CIML and CIPHE mouse houses, Atika Zouine, Marc Barad, and Sylvain Bigot of the CIML flow cytometry facility, Mathieu Fallet of the CIML microscopy facility, and the France-BioImaging infrastructure supported by the Agence Nationale de la Recherche (ANR-10-INSB-04-01, call "Investissements d'Avenir"). We thank Violaine Alunni and Christelle Thibault-Carpentier from Plate-forme Genomeast (Strasbourg, France) for microarray experiments (http://www.igbmc.fr/technologies/5/team/54/), and Pr. Stipan Jonjic for the anti-MCMV Croma antibody. We thank Frederic Fiore, Bernard Malissen, and all the staff of Centre d'Immunophenomique [CIPHE] (UM2 Aix-Marseille Universite, Institut National de la Sante et de la Recherche Medicale US012, Centre National de la Recherche Scientifique UMS3367, Marseille, France) for generating mutant mice. We acknowledge Pr. Tadatsugu Taniguchi (University of Tokyo, Japan), Dr. Claude Leclerc, and Dr. Molly Ingersoll (Institut Pasteur, Paris) for generous gift of mutant mice and/or critical reading of the manuscript. This work benefited from data assembled by the ImmGen consortium. This research was funded by grants from the European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013 Grant Agreement 281225, "SystemsDendritic"), the Fondation pour la Recherche Medicale (FRM, reference DEQ20110421284), and the Agence Nationale de la Recherche (ANR) (SCAPIN, ANR-15-CE15-0006-01). We also acknowledge support from the DCBIOL Labex (ANR-11-LABEX-0043, grant ANR-10-IDEX-0001-02 PSL*), the A*MIDEX project (ANR-11-IDEX-0001-02) funded by the French Government's "Investissements d'Avenir" program managed by the ANR, and institutional support from CNRS, Inserm, Aix Marseille Universite, and Marseille Immunopole.