Activation of the TLR3 pathway regulates IFNbeta production in chickens.
Toll-like receptors (TLRs) play key roles in the response to pathogens and in mammals the host response to virus critically relies on TLR3 to detect viral-derived dsRNA. However, in chickens there is a paucity of information about this pathway, and in view of the recent concerns with regard to highly pathogenic avian influenza, there is a clear need for understanding these antiviral pathways. Furthermore, TLR3 engagement is important to the outcome of viral infection because of its role in the induction of interferons (IFNs) and the diverse antiviral effects that these molecules induce. With this in mind, we have investigated the role of TLR3 and its impact on the production of IFNs. We show that in the chicken, poly(I:C), a dsRNA analogue, rapidly induces type 1 IFN similar to that seen in mammals. Furthermore, IFN can activate the upregulation of TLR3, which in some cell types induces them to become responsive to dsRNA. These data highlight the similar function that TLR3 plays in chickens and mammals. To determine the role of chicken TLR3 in response to poly(I:C), we used RNAi-mediated gene silencing to show that poly(I:C)-stimulated IFNbeta expression involves TLR3 signalling. The interrelationship between TLR3 and interferon as well as the observed increase in TLR3 and IFNbeta expression during H5N1 avian influenza infection indicates the importance of these molecules in viral infections in chickens.
Karpala
Adam J
AJ
CSIRO, Livestock Industries, AAHL, 5, Portarlington Road, Victoria 3220, Australia. adam.karpala@csiro.au
Lowenthal
John W
JW
Bean
Andrew G
AG
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002645:Chickens / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology*; D007369:Interferon Inducers / Q000494:pharmacology; D016898:Interferon-alpha / Q000276:immunology; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
D007369:Interferon Inducers; D016898:Interferon-alpha; D034741:RNA, Small Interfering; D051196:Toll-Like Receptor 3; D016899:Interferon-beta; D011070:Poly I-C