Abstract |
Plasmacytoid dendritic cells (pDCs) play a critical role in antiviral immunity through their ability to produce large amounts of type I IFNs. Activation of pDCs upon viral infection has been shown to be dependent on MyD88 and mediated by Toll-like receptors (TLR) 7 and 9, which sense viral ssRNA and CpG DNA, respectively. In this study, we showed that murine pDC recognition of vaccinia virus (VV), a dsDNA virus, was MyD88-dependent but TLR9-independent. Using HEK293 cells transfected with murine TLR7 or TLR8 and a NF-kappaB luciferase reporter, we demonstrated that stimulation of TLR8-, but not TLR7-, transfected cells with either VV or VV DNA resulted in substantial NF-kappaB activation, and that siRNA-mediated knockdown of TLR8 expression in pDCs led to a complete ablation of VV-induced type I IFN production. We further identified that the VV genome was rich in poly(A)/T sequences, and synthetic poly(A) and poly T oligodeoxynucleotides were capable of activating pDCs in a TLR8-dependent manner. In vivo, TLR8-MyD88-dependent pDC activation played a critical role in innate immune control of VV infection. Collectively, our data are unique in demonstrating that TLR8 is required for sensing poly(A)/T-rich DNA in pDCs, and that murine TLR8 is functional in the context of a viral infection.
|
Authors | Jennifer Martinez, Xiaopei Huang, Yiping Yang |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 107
Issue 14
Pg. 6442-7
(Apr 06 2010)
ISSN: 1091-6490 [Electronic] United States |
PMID | 20308556
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- DNA, Viral
- Myd88 protein, mouse
- Myeloid Differentiation Factor 88
- Tlr9 protein, mouse
- Toll-Like Receptor 8
- Toll-Like Receptor 9
|
Topics |
- Animals
- Cells, Cultured
- DNA, Viral
(immunology)
- Dendritic Cells
(immunology)
- Humans
- Immunity, Innate
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Myeloid Differentiation Factor 88
(deficiency, immunology)
- Toll-Like Receptor 8
(immunology)
- Toll-Like Receptor 9
(deficiency, immunology)
- Vaccinia
(immunology)
- Vaccinia virus
(immunology)
|