title: Viral infection switches non-plasmacytoid dendritic cells into high interferon producers.
abstract: Type I interferons (IFN-I) are important cytokines linking innate and adaptive immunity. Plasmacytoid dendritic cells make high levels of IFN-I in response to viral infection and are thought to be the major source of the cytokines in vivo. Here, we show that conventional non-plasmacytoid dendritic cells taken from mice infected with a dendritic-cell-tropic strain of lymphocytic choriomeningitis virus make similarly high levels of IFN-I on subsequent culture. Similarly, non-plasmacytoid dendritic cells secrete high levels of IFN-I in response to double-stranded RNA (dsRNA), a major viral signature, when the latter is introduced into the cytoplasm to mimic direct viral infection. This response is partially dependent on the cytosolic dsRNA-binding enzyme protein kinase R and does not require signalling through toll-like receptor (TLR) 3, a surface receptor for dsRNA. Furthermore, we show that sequestration of dsRNA by viral NS1 (refs 6, 7) explains the inability of conventional dendritic cells to produce IFN-I on infection with influenza. Our results suggest that multiple dendritic cell types, not just plasmacytoid cells, can act as specialized interferon-producing cells in certain viral infections, and reveal the existence of a TLR-independent pathway for dendritic cell activation that can be the target of viral interference.
authors.affiliation: Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Diebold
authors.forename: Maria
authors.initials: M
authors.lastname: Montoya
authors.forename: Hermann
authors.initials: H
authors.lastname: Unger
authors.forename: Lena
authors.initials: L
authors.lastname: Alexopoulou
authors.forename: Polly
authors.initials: P
authors.lastname: Roy
authors.forename: Linsey E
authors.initials: LE
authors.lastname: Haswell
authors.forename: Aymen
authors.initials: A
authors.lastname: Al-Shamkhani
authors.forename: Richard
authors.initials: R
authors.lastname: Flavell
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
mesh_terms: D016475:3T3 Cells; D000818:Animals; D018899:CpG Islands / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012330:RNA, Double-Stranded / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D007370:Interferon Type I; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D012330:RNA, Double-Stranded; D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D019892:eIF-2 Kinase