Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells
Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells
Science 315, 1398-1401 (2007)
Speaker: 張有德 Time: 15:00-16:00; May 23, 2007
Commentator: 陳舜華老師 Place: room 601
Abstract:
Plasmacytoid dendritic cells (pDCs) are a unique lineage of dendritic cells because they have some interesting features to distinguish them from other conventional dendriticcells (cDCs). pDCs rely on TLRs more than the cytosolic dsRNA sensors such as retinoic acid inducible gene 1 (RIG-1) and protein kinase R (PKR). It has been reported that respiratory syncytial virus (RSV)-induced IFN-α production by pDCs depends on active viral replication and the fusion of virus with the host membrane, but it is independent ofendosome maturation and PKR2. This result suggested that pDCs are able to detect some ssRNA virus such as RSV in the cytosol by an unknown mechanism. In this article the authors first demonstrated that infection of vesicular stomatitis virus (VSV) and detection by TLR7 is absolutely required for IFN-α production by mice pDCs. Next the authors demonstrated the entry of matrix protein into the cytosol, which indicated that viral replication intermediates generated after viral fusion may be the inducer of IFN-α production bypDCs after VSV infection. Since autophagy is a process of enclosing cytosolic materials by the membrane and afterward fusing with endosome, the authors used inhibitor ofautophagy, 3-methyladenine (3-MA) and Wortmannin, and ATG5-/- chimera mice to determine whether autophagy is involved during the process of viral recognition. Finally authors concluded that it is autophagy mediating the recognition of VSV replication intermediates in the cytosol and the production of IFN-α by pDCs, and they also suggested thatcytosolic replication intermediates of virus might be enclosed by autophagic vacuoles, therefore serve as infection signatures recognized by TLR7.
References:
1. M. Colonna, G. Trinchieri & Yong-Jun Liu. Plasmacytoid dendritic cells in immunity. Nat. Rev. Immunol. 5. 1219-1226 (2004).
2. V. Hornung, J. Schlender, M. Guenthner-Biller, S. Rothenfusser, S. Endres, K-K Conzelmann, and G. Hartmann. Replication-Dependent Potent IFN-a Induction in HumanPlasmacytoid Dendritic Cells by a Single-Stranded RNA Virus. J. Immunol. 173. 5935-5943 (2004)