Molecular dissection of plasmacytoid dendritic cell activation in vivo during a viral infection - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2018

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

Résumé

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.
Fichier principal
Vignette du fichier
embj.201798836.pdf (3.2 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-02117981 , version 1 (25-10-2019)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Elena Tomasello, Karima Naciri, Rabie Chelbi, Gilles Bessou, Anissa Fries, et al.. Molecular dissection of plasmacytoid dendritic cell activation in vivo during a viral infection. EMBO Journal, 2018, 37 (19), ⟨10.15252/embj.201798836⟩. ⟨hal-02117981⟩
44 Consultations
58 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More