| All strains of influenza replicate in the duck, the natural host of the virus. Ducks suffer little pathology from most influenza viruses, while the same strains are often fatal to chickens. The reasons why ducks and chickens have differing susceptibilities to influenza are not known. We speculated that innate immune mechanisms are particularly important for influenza defense to highly pathogenic avian influenza (HPAI) in ducks, due to the acute nature of this infection. We identified and characterized the known influenza detectors, toll like receptor 7 (TLR7) and retinoic-acid inducible gene-I (RIG-I) in ducks, to examine their early innate immune response to influenza. A comparison to chickens showed that ducks have a similar genomic organization of TLR7. However, the function of TLR7 differs between ducks and chickens. Ducks, but not chickens, express TLR7 in the lung and always induce IFNalpha upon TLR7 triggering. Ducks have a functional RIG-I, while the gene appears to have been lost in chickens, affording them superior antiviral pattern recognition. Transferring duck RIG-I to chicken cells allows for recognition of RIG-I ligand, decreases low pathogenic avian influenza (LPAI) and HPAI virus titre, and induces antiviral gene transcription. Thus, differences in the expression, function and even the repertoire of influenza-detecting pattern recognition receptors may all contribute to the relative resistance of ducks and susceptibility of chickens to influenza pathology. Understanding the immunological mechanisms mediating influenza resistance in ducks may provide insight into what constitutes a successful response to this virus. |