Atlantic salmon type I IFN subtypes show differences in antiviral activity and cell-dependent expression: evidence for high IFNb/IFNc-producing cells in fish lymphoid tissues

This work reveals distinct roles of the two-cysteine-containing type I IFNs, IFNa and IFNd, and the four-cysteine-containing IFNb and IFNc in antiviral immunity of Atlantic salmon. IFNa and IFNc showed similar antiviral activities and ability to induce antiviral genes, IFNb was less active, and IFNd...

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Published in:	The Journal of immunology (1950) Vol. 189; no. 12; pp. 5912 - 5923
Main Authors:	Svingerud, Tina, Solstad, Terese, Sun, Baojian, Nyrud, May Liss J, Kileng, Øyvind, Greiner-Tollersrud, Linn, Robertsen, Børre
Format:	Journal Article
Language:	English
Published:	United States 15-12-2012
Subjects:	Animals DEAD-box RNA Helicases - genetics DEAD-box RNA Helicases - physiology Fish Proteins - genetics Fish Proteins - physiology HEK293 Cells Humans Interferon Type I - genetics Interferon Type I - physiology Interferon-Induced Helicase, IFIH1 Lymphoid Tissue - immunology Lymphoid Tissue - metabolism Lymphoid Tissue - virology Primary Cell Culture Promoter Regions, Genetic - immunology Receptors, Retinoic Acid - genetics Receptors, Retinoic Acid - physiology Salmo salar Salmo salar - immunology Signal Transduction - immunology
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Summary:	This work reveals distinct roles of the two-cysteine-containing type I IFNs, IFNa and IFNd, and the four-cysteine-containing IFNb and IFNc in antiviral immunity of Atlantic salmon. IFNa and IFNc showed similar antiviral activities and ability to induce antiviral genes, IFNb was less active, and IFNd showed no activity. Expression of IFNs was compared by treatment of cells or fish with the dsRNA polyinosinic-polycytidylic acid [poly(I:C)], which induces IFNs via the viral RNA receptors MDA5 and TLR3/TLR22 and with the imidazoquinoline R848, which induces IFNs via TLR7. Poly(I:C) strongly induced IFNa in cell lines, whereas the other IFNs showed little response, indicating that IFNa is the main IFN subtype induced through the RIG-I/MDA5 pathway. In contrast, IFNb and IFNc are the main IFNs induced through the TLR7 pathway because R848 induced high transcript levels of IFNb and IFNc and low transcript levels of IFNa in the head kidney and spleen. IFNd was constitutively expressed in cells and organs but showed no response to poly(I:C) or R848. Fluorescence in situ hybridization studies showed that poly(I:C) induced IFNa and IFNc in a variety of cells in the head kidney, spleen, gills, liver, and heart, whereas R848 induced coexpression of IFNb and IFNc in distinct cells in head kidney and spleen. These cells are likely to be specialized high IFN producers because they were few in numbers despite high IFNb/IFNc transcript levels in the same organs. High IFN expression in response to TLR7 ligation is a feature shared by mammalian plasmacytoid dendritic cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.1201188