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

• Elena Tomasello ^[1] ; Karima Naciri ^[1] ; Rabie Chelbi ^[1] ; Gilles Bessou ^[1] ; Anissa Fries ^[2] ; Elise Gressier ^[3] ; Abdenour Abbas ^[1] ; Emeline Pollet ^[1] ; Philippe Pierre ^[1] ; Toby Lawrence ^[1] ; Thien‐Phong Vu Manh ^[1] ; Marc Dalod ^[1]
  1. [1] 1 Aix Marseille Univ CNRS INSERM CIML Centre d'Immunologie de Marseille‐Luminy Marseille France
  2. [2] 1 Aix Marseille Univ CNRS INSERM CIML Centre d'Immunologie de Marseille‐Luminy Marseille France; 2Present address: Department of Dermatology University Hospital CHUV Lausanne Switzerland
  3. [3] 1 Aix Marseille Univ CNRS INSERM CIML Centre d'Immunologie de Marseille‐Luminy Marseille France; 3Present address: Department of Microbiology and Immunology Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville Vic. Australia

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 37, Nº. 19, 2018
• Idioma: inglés
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  • 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 necessary for robust cytokine production. In contrast, we show here that in vivo during mouse cytomegalovirus (MCMV) infection pDC produce high amounts of IFN‐I downstream of the TLR9‐to‐MyD88‐to‐IRF7 signaling pathway without requiring IFN‐I positive feedback, high IRF7 expression, or AP3‐driven endosomal routing of TLRs. Hence, the current model of the molecular requirements for professional IFN‐I production by pDC, established by using synthetic TLR ligands, does not strictly apply to a physiological viral infection.