Viral infection switches non-plasmacytoid dendritic cells into high interferon producers.
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.
Diebold
Sandra S
SS
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3PX, UK.
Montoya
Maria
M
Unger
Hermann
H
Alexopoulou
Lena
L
Roy
Polly
P
Haswell
Linsey E
LE
Al-Shamkhani
Aymen
A
Flavell
Richard
R
Borrow
Persephone
P
Reis e Sousa
Caetano
C
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
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