The role of IRF7 and NF-κB pathways in the induction of antiviral responses in chicken tracheal epithelial cells following exposure to TLR3 and 4 ligands

Abstract

Abstract With recent outbreaks of avian influenza viruses (AIV), there is a need for better understanding of host responses in the respiratory system to AIV in order to develop and improve prophylactic procedures for control of AIV. Toll-like receptors (TLRs) are molecules in the immune system that rapidly induce antiviral responses in the host. Activation of TLRs by their ligands leads to a variety of cellular responses, including the production of interferons (IFNs). However, there is little information about induced antiviral responses in chicken trachea following TLR ligand treatment. We cultured primary chicken tracheal epithelial cells (cTECs) to determine antiviral responses induced by TLR3 and 4 ligands. These cells were treated with polyI:C and LPS from Escherichia coli 026:B6, TLR3 and 4 ligands respectively, before AIV infection. We also used BX795 and celastrol, inhibitors of IRF7 and NF-κB pathways, respectively, in order to gain insight into the mechanisms involved in the induced antiviral responses. Our results showed that treatment of cTECs with TLR ligands reduced the replication of AIV in cTECs. Treatment of cTECs with polyI:C resulted in highest reduction of viral replication in cTECs followed by treatment of cTECs with LPS. BX795 increased AIV replication in polyI:C and LPS treated cells while celastrol increased AIV replication in polyI:C treated cells. Overall, these results provided evidence that cTECs are able to mount antiviral responses against AIV after TLR ligand stimulation. Moreover, we determined the role of IRF7 and NF-κB signalling pathways in the induction of antiviral responses. Studies are underway to examine the ability of cTECs to produce type I IFNs and the effect of other cells, such as macrophages, on cTECs.