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

Letter to Nature. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers
Letter to Nature. 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 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.
0028-0836
324-328
Diebold, Sandra S.
f1e39d9e-cfd1-4e43-b66a-4dde63a9d56b
Montoya, Maria
0620e3ca-7e29-4591-a359-a94a3d243399
Unger, Hermann
5a745258-f488-44cb-8da9-ac8c62693ad9
Alexopoulou, Lena
a0717406-c518-4a40-aabc-555df341608c
Roy, Polly
eb7049e7-5c35-4325-8a19-badd4a9fe777
Haswell, Linsey E.
7e2a20d5-8dda-42dd-a956-962ce5446337
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Flavell, Richard
bb7ce742-4756-43c8-8639-25e35279451d
Borrow, Persephone
e6eb6b06-b8f9-47bc-af78-d3eb04e8cf9b
Reis e Sousa, Caetano
10599377-1e7b-47ca-bffd-3bc8521acdda
Diebold, Sandra S.
f1e39d9e-cfd1-4e43-b66a-4dde63a9d56b
Montoya, Maria
0620e3ca-7e29-4591-a359-a94a3d243399
Unger, Hermann
5a745258-f488-44cb-8da9-ac8c62693ad9
Alexopoulou, Lena
a0717406-c518-4a40-aabc-555df341608c
Roy, Polly
eb7049e7-5c35-4325-8a19-badd4a9fe777
Haswell, Linsey E.
7e2a20d5-8dda-42dd-a956-962ce5446337
Al-Shamkhani, Aymen
0a40b3ce-9d71-4d41-9369-7212f0a84504
Flavell, Richard
bb7ce742-4756-43c8-8639-25e35279451d
Borrow, Persephone
e6eb6b06-b8f9-47bc-af78-d3eb04e8cf9b
Reis e Sousa, Caetano
10599377-1e7b-47ca-bffd-3bc8521acdda

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).

Record type: Article

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 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

Identifiers

Local EPrints ID: 26279
URI: http://eprints.soton.ac.uk/id/eprint/26279
ISSN: 0028-0836
PURE UUID: 79d79094-41b2-4f58-9fe5-19656e316b23
ORCID for Aymen Al-Shamkhani: ORCID iD orcid.org/0000-0003-0727-4189

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Date deposited: 24 Apr 2006
Last modified: 16 Mar 2024 03:02

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Contributors

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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