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TLR9 transcriptional regulation in response to double-stranded DNA viruses.

Authors :
Zannetti C
Parroche P
Panaye M
Roblot G
Gruffat H
Manet E
Debaud AL
Plumas J
Vey N
Caux C
Bendriss-Vermare N
Hasan UA
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Oct 01; Vol. 193 (7), pp. 3398-408. Date of Electronic Publication: 2014 Sep 05.
Publication Year :
2014

Abstract

The stimulation of TLRs by pathogen-derived molecules leads to the production of proinflammatory cytokines. Because uncontrolled inflammation can be life threatening, TLR regulation is important; however, few studies have identified the signaling pathways that contribute to the modulation of TLR expression. In this study, we examined the relationship between activation and the transcriptional regulation of TLR9. We demonstrate that infection of primary human epithelial cells, B cells, and plasmacytoid dendritic cells with dsDNA viruses induces a regulatory temporary negative-feedback loop that blocks TLR9 transcription and function. TLR9 transcriptional downregulation was dependent on TLR9 signaling and was not induced by TLR5 or other NF-κB activators, such as TNF-α. Engagement of the TLR9 receptor induced the recruitment of a suppressive complex, consisting of NF-κBp65 and HDAC3, to an NF-κB cis element on the TLR9 promoter. Knockdown of HDAC3 blocked the transient suppression in which TLR9 function was restored. These results provide a framework for understanding the complex pathways involved in transcriptional regulation of TLR9, immune induction, and inflammation against viruses.<br /> (Copyright © 2014 by The American Association of Immunologists, Inc.)

Details

Language :
English
ISSN :
1550-6606
Volume :
193
Issue :
7
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
25194054
Full Text :
https://doi.org/10.4049/jimmunol.1400249