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Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells

作者:Heung Kyu Lee, Jennifer M. Lund, Balaji Ramanathan, Noboru Mizushima, Akiko Iwasaki · 发表于:Science · 年份:2007 · DOI:10.1126/science.1136880 · 被引用次数:846 · 研究领域:Cytomegalovirus and herpesvirus research、Immunotherapy and Immune Responses、interferon and immune responses

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.