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Letter to Nature. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers

Diebold, Sandra S., Montoya, Maria, Unger, Hermann, Alexopoulou, Lena, Roy, Polly, Haswell, Linsey E., Al-Shamkhani, Aymen, Flavell, Richard, Borrow, Persephone and Reis e Sousa, Caetano (2003) Letter to Nature. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers Nature, 424, (6946), pp. 324-328. (doi:10.1038/nature01783).

Record type: Article


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 R4 and does not require signalling through toll-like receptor (TLR), a surface receptor for dsRNA5. Furthermore, we show that sequestration of dsRNA by viral NS1 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.

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Published date: 2003


Local EPrints ID: 26279
ISSN: 0028-0836
PURE UUID: 79d79094-41b2-4f58-9fe5-19656e316b23

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Date deposited: 24 Apr 2006
Last modified: 17 Jul 2017 16:07

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Author: Sandra S. Diebold
Author: Maria Montoya
Author: Hermann Unger
Author: Lena Alexopoulou
Author: Polly Roy
Author: Linsey E. Haswell
Author: Richard Flavell
Author: Persephone Borrow
Author: Caetano Reis e Sousa

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