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

Journal 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 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.

Authors: Diebold, S; Montoya, M; Unger, H; Alexopoulou, L; Roy, P

• Publication status: Published
• Journal: Nature
• Volume: 424
• Issue: 6946
• Pages: 324-328
• Publication date: 2003-07-01
• DOI: 10.1038/nature01783
• EISSN: 1476-4687
• ISSN: 0028-0836
• Language: English
• Keywords: Membrane Glycoproteins; Animals; eIF-2 Kinase; Dendritic Cells; Signal Transduction; Receptors, Cell Surface; Interferon Type I; Mice; Mice, Inbred C57BL; Mice, Inbred BALB C; CpG Islands; RNA, Double-Stranded; Toll-Like Receptors; Lymphocytic Choriomeningitis; Interferon-alpha; Toll-Like Receptor 3; Lymphocytic choriomeningitis virus; 3T3 Cells