title: Autophagy-dependent viral recognition by plasmacytoid dendritic cells.
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.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Heung Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Lund
authors.forename: Balaji
authors.initials: B
authors.lastname: Ramanathan
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
mesh_terms: D000818:Animals; D001343:Autophagy; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology / Q000821:virology*; D011992:Endosomes / Q000276:immunology / Q000821:virology; D005260:Female; D007113:Immunity, Innate; D016898:Interferon-alpha / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008247:Lysosomes / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010588:Phagosomes / Q000502:physiology / Q000648:ultrastructure; D012367:RNA, Viral / Q000276:immunology* / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication
chemical_list: D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D012367:RNA, Viral; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D018664:Interleukin-12