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), 324-328. (doi:10.1038/nature01783).
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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 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.
|Digital Object Identifier (DOI):||doi:10.1038/nature01783|
|Subjects:||Q Science > QR Microbiology > QR355 Virology
Q Science > QH Natural history > QH426 Genetics
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Cancer Sciences
|Date Deposited:||24 Apr 2006|
|Last Modified:||31 Mar 2016 11:49|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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