Abstract
Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-α by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-α secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.
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- We are grateful to J. Publicover and J. Rose for reagents and expertise R. Medzhitov for critical review of the manuscript W. Mothes for helpful discussions and M. Zamora and G. Lyon for technical assistance. We thank P. J. Morrissey B. Hall and T. C. George of Amnis Corporation for analysis of samples using Image Stream technology. This work was supported by Public Health Service grants AI054359 and AI064705 (to A.I.) from NIH. J.M.L. was supported by the training grant AI07019 from NIH. H.K.L. was supported by the Ministry of Science and Technology of Korea. A.I. holds an Investigators in Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund.
Dates
Type | When |
---|---|
Created | 18 years, 6 months ago (Feb. 3, 2007, 2:58 a.m.) |
Deposited | 1 year, 7 months ago (Jan. 10, 2024, 4:31 a.m.) |
Indexed | 1 day, 17 hours ago (Aug. 23, 2025, 1:02 a.m.) |
Issued | 18 years, 5 months ago (March 9, 2007) |
Published | 18 years, 5 months ago (March 9, 2007) |
Published Print | 18 years, 5 months ago (March 9, 2007) |
@article{Lee_2007, title={Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells}, volume={315}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1136880}, DOI={10.1126/science.1136880}, number={5817}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Lee, Heung Kyu and Lund, Jennifer M. and Ramanathan, Balaji and Mizushima, Noboru and Iwasaki, Akiko}, year={2007}, month=mar, pages={1398–1401} }