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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.

Original publication

DOI

10.1038/nature01783

Type

Journal article

Journal

Nature

Publication Date

17/07/2003

Volume

424

Pages

324 - 328

Keywords

3T3 Cells, Animals, CpG Islands, Dendritic Cells, Interferon Type I, Interferon-alpha, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, RNA, Double-Stranded, Receptors, Cell Surface, Signal Transduction, Toll-Like Receptor 3, Toll-Like Receptors, eIF-2 Kinase