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Molecular dissection of plasmacytoid dendritic cell activation in vivo during a viral infection
Author(s) -
Tomasello Elena,
Naciri Karima,
Chelbi Rabie,
Bessou Gilles,
Fries Anissa,
Gressier Elise,
Abbas Abdenour,
Pollet Emeline,
Pierre Philippe,
Lawrence Toby,
Vu Manh ThienPhong,
Dalod Marc
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798836
Subject(s) - biology , in vivo , dendritic cell , virology , immunology , microbiology and biotechnology , immune system , genetics
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 ( TLR s) 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 AP 3 is necessary to transport molecular complexes of TLR s, synthetic CpG DNA , and MyD88 into endosomal compartments allowing interferon regulatory factor 7 ( IRF 7) recruitment whose phosphorylation then initiates IFN ‐I production. High basal expression of IRF 7 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 TLR 9‐to‐MyD88‐to‐ IRF 7 signaling pathway without requiring IFN ‐I positive feedback, high IRF 7 expression, or AP 3‐driven endosomal routing of TLR s. 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.