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Science 315 (5817): 1398-1401

Copyright © 2007 by the American Association for the Advancement of Science

Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells

Heung Kyu Lee,1* Jennifer M. Lund,1*{dagger} Balaji Ramanathan,1* Noboru Mizushima,2,3 Akiko Iwasaki1{ddagger}

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-{alpha} by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-{alpha} secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.

1 Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
2 Department of Cell Physiology, Tokyo Medical and Dental University, Graduate School and Faculty of Medicine, Tokyo, Japan.
3 Solution-Oriented Research for Science and Technology, Japan Science and Technology Agency, Kawaguchi, Japan.

* These authors contributed equally to this work.

{dagger} Present address: Department of Immunology, University of Washington, Seattle, WA.

{ddagger} To whom correspondence should be addressed: akiko.iwasaki{at}yale.edu

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