RNA-sensing toll-like receptors (TLRs) mediate innate immunity and regulate anti-viral response. We show here that TLR3 regulates host immunity and the loss of TLR3 aggravates pathology in Chikungunya virus (CHIKV) infection. Susceptibility to CHIKV infection is markedly increased in human and mouse fibroblasts with defective TLR3 signaling. Up to 100-fold increase in CHIKV load was observed in...

Periodontal ligament stem cells (PDLSCs) have been served as a cell reservoir for tissue regeneration during adulthood. For clinical applications, the challenging steps are to maintain the stem cell properties and to improve the regeneration capacity of PDLSCs during culture. Toll-like receptor 3 (TLR3) signaling has been shown to enhance therapeutic potential in several cell types including me...

Activation of TLR3 has long been studied in the field of anticancer immunotherapy. Our recent work revealed that TLR3 also promotes the induction of breast cancer stem cells (CSCs) through co-activation of β-catenin and NF-κB signaling. Targeting these 2 pathways simultaneously instead of individually allows for effective inhibition of CSCs that are enhanced by TLR3 activation.

BACKGROUND Hepatocellular carcinoma (HCC) is a highly aggressive cancer that is linked to chronically dysregulated liver inflammation. However, appropriate immune responses can control HCC progression. Here we investigated the role and underlying mechanism of toll-like receptor 3 (TLR3) in HCC. METHODS HCC cell death, and natural killer (NK) cell activation and cytotoxicity were assessed in v...

Despite extensive studies that unraveled ligands and signal transduction pathways triggered by TLRs, little is known about the regulation of TLR gene expression. TLR3 plays a crucial role in the recognition of viral pathogens and induction of immune responses by myeloid DCs. IFN regulatory factor (IRF)-8, a member of the IRF family, is a transcriptional regulator that plays essential roles in t...

BACKGROUND Toll-like receptor 3 (TLR3) was originally identified as the receptor for viral RNA and represents a major host antiviral defense mechanism. TLR3 may also recognize extracellular RNA (exRNA) released from injured tissues under certain stress conditions. However, a role for exRNA and TLR3 in the pathogenesis of myocardial ischemic injury has not been tested. This study examined the ro...

Toll-like receptor 3 (TLR3) variants in mainland northern Chinese patients with polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (nAMD) were investigated. The complete genes of TLR3, including all exons and the promoter region, were assessed using direct sequencing technology of 284 unrelated mainland northern Chinese individuals: 96 nAMD patients, 92 PCV...

Herpes simplex encephalitis (HSE) is a severe neurological disease in children and adults caused by herpes simplex virus. This review discusses recent findings on the role of Toll-like receptor 3 (TLR3) deficiencies in the HSE development. Critical checkpoints in the TLR3 signaling that contribute to innate response are discussed, including the importance of TLR3 ligand recognition site and tra...

UV damage to the skin leads to the release of noncoding RNA (ncRNA) from necrotic keratinocytes that activates Toll-like receptor 3 (TLR3). This release of ncRNA triggers inflammation in the skin following UV damage. Recently, TLR3 activation was also shown to aid wound repair and increase the expression of genes associated with permeability barrier repair. Here, we sought to test whether skin ...

Maturation of dendritic cells (DC) to competent APC is essential for the generation of acquired immunity and is a major function of adjuvants. dsRNA, a molecular signature of viral infection, drives DC maturation by activating TLR3, but the size of dsRNA required to activate DC and the expression patterns of TLR3 protein in DC subsets have not been established. In this article, we show that cro...