Molecular dissection of plasmacytoid dendritic cell activation
| Autor: | Elena, Tomasello, Karima, Naciri, Rabie, Chelbi, Gilles, Bessou, Anissa, Fries, Elise, Gressier, Abdenour, Abbas, Emeline, Pollet, Philippe, Pierre, Toby, Lawrence, Thien-Phong, Vu Manh, Marc, Dalod |
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| Rok vydání: | 2017 |
| Předmět: |
Mice
Knockout Muromegalovirus Membrane Glycoproteins Adaptor Protein Complex 3 Interferon Regulatory Factor-7 Immunology hemic and immune systems Dendritic Cells Endosomes Herpesviridae Infections Articles Article mouse cytomegalovirus Microbiology Virology & Host Pathogen Interaction Mice Toll-Like Receptor 7 type I interferons plasmacytoid dendritic cells Toll-Like Receptor 9 Interferon Type I Myeloid Differentiation Factor 88 IRF7 Animals viral infection Signal Transduction |
| Zdroj: | The EMBO Journal |
| ISSN: | 1460-2075 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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