Double-stranded RNA induces chicken T-cell lymphoma apoptosis by TRIF and NF-κB

Abstract

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.

Modulatory Effects of Pb2+ on Virally Challenged Chicken Macrophage (HD‐11) and B‐Lymphocyte (DT40) Cell Lines In Vitro

“…Two chicken immune cell lines, macrophage HD‐11 cells and B‐lymphocyte DT40 cells, were selected as 2 avian in vitro models for the innate and adaptive immune systems, respectively. Because both cell lines express toll‐like receptor 3 (TLR3), which is able to recognize double‐stranded RNA (dsRNA) related to viral infection (Peroval et al 2013; Zou et al 2017), polyinosinic–polycytidylic acid sodium salt (poly I:C), a synthetic analog of dsRNA (Chen et al 2013) was used as a viral activator via TLR3.…”

Efficient Mutagenesis of Marek’s Disease Virus-Encoded microRNAs Using a CRISPR/Cas9-Based Gene Editing System

“…Based on the type II CRISPR-Cas system consisting of a single guide RNA (sgRNA), a trans-activating crRNA (tracrRNA) and a RNA-guided endonuclease Cas9 derived from Streptococcus pyogenes, the latest developed CRISPR/Cas9 gene editing technique has been displayed as a simple, efficient and powerful tool for gene editing in biological research [33][34][35]. It has not only been widely applied for generating gene knockout (KO) cell lines and animal models, but has also been used for manipulating large viral DNA genomes, such as Epstein-Barr virus (EBV) [36], herpes simplex virus type I (HSV-1) [32,37,38], guinea pig cytomegalovirus (GPCMV) [39], pseudorabies virus (PrV) [40][41][42], vaccinia virus (VACV) [43,44], and duck enteritis virus (DEV) [45,46]. We have successfully demonstrated the manipulation of the HVT and MDV-1 genomes using the CRISPR/Cas9 system both for generating recombinant vaccines and for studying the viral protein-coding gene functions respectively [47][48][49][50][51].…”

High expression of TLR3 in triple-negative breast cancer predicts better prognosis—data from the Fudan University Shanghai Cancer Center cohort and tissue microarrays

“…TLR3 stimulation with dsRNA is considered to directly promote tumor-cell apoptosis in many types of cancer, such as breast, melanoma, prostate, cervical, colon, and hepatocellular carcinoma [ 23 – 25 ]. Poly (I:C), a TLR3 activator, directly causes apoptosis in cancer cells via a caspase-dependent pathway [ 26 , 27 ].…”