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TLR9 transcriptional regulation in response to double-stranded DNA viruses.
- 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.)
- Subjects :
- Animals
DNA Virus Infections genetics
DNA Virus Infections pathology
Dendritic Cells immunology
Dendritic Cells pathology
Epithelial Cells immunology
Epithelial Cells pathology
Female
Gene Knockdown Techniques
HEK293 Cells
Histone Deacetylases genetics
Histone Deacetylases immunology
Humans
Male
Mice
NIH 3T3 Cells
Plasma Cells immunology
Plasma Cells pathology
Toll-Like Receptor 9 genetics
Transcription Factor RelA genetics
Transcription Factor RelA immunology
Transcription, Genetic genetics
DNA Virus Infections immunology
DNA Viruses immunology
Promoter Regions, Genetic immunology
Toll-Like Receptor 9 immunology
Transcription, Genetic immunology
Subjects
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