Marek’s disease virus (MDV) is an α-herpesvirus that causes immune suppression and T lymphoma in chickens. Toll-like receptor 3 (TLR3) is critical for the host immune response against MDV infection. Previously, our team demonstrated that pre-treatment of TLR3 agonist poly (I:C) inhibited Marek’s disease virus infection in chicken embryo fibroblasts (CEFs). However, whether TLR3 inhibits the aggravation of MDV infection is unknown. In the current study, we found that TLR3 activation in MDV-infected CEFs effectively inhibited virus spread. Using pharmacological approaches, we revealed that pro-inflammatory cytokines and interferon-β induced by TLR3 could restrict Marek’s disease virus infection. This study contributes to elucidating the function and mechanism of the TLR3 pathway in host immune responses against MDV infection.

Toll-like receptor-3 (TLR3), a member of the pathogen recognition receptor family, has been reported to activate immune response and to exhibit pro-apoptotic activity against some tumor cells. However it is unclear whether TLR3 has same function against chicken lymphoma. In this paper we investigated the effect of TLR3 activation on a Marek’s disease lymphoma-derived chicken cell line, MDCC-MSB1. The TLR3 agonist poly (I:C) activated TLR3 pathway and inhibited tumor cells proliferation through caspase-dependent apoptosis. Using pharmacological approaches, we found that an interferon-independent mechanism involving Toll-IL-1-receptor domain-containing adapter-inducing IFN-α (TRIF) and nuclear factor κB (NF-κB) causes the apoptosis of MDCC-MSB1 cells. This is the first report about the function of TLR3 in chicken T-cell lymphoma, especially in signal pathway. The mechanisms underlying TLR3-mediated apoptosis may contribute to the development of new drug to treat lymphomas and oncovirus infections.