TLR3 activation efficiency by high or low molecular mass poly I:C

Abstract

Toll-like receptor 3 (TLR3) plays a critical role in initiating type I IFN-mediated innate immunity against viral infections. TLR3 recognizes various forms of double stranded (ds) RNA, including viral dsRNA and a synthetic mimic of dsRNA, poly I:C, which has been used extensively as a TLR3 ligand to induce antiviral immunity. The activation efficiency of TLR3 by poly I:C is influenced by various factors, including size of the ligands, delivery methods and cell types. In this study, we examined the stimulatory effect of two commercially-available poly I:Cs [high molecular mass (HMM) and low molecular mass (LMM)] on TLR3 activation in various human cell types by determining the induction of type I and type III IFNs, as well as the antiviral effect. We demonstrated that the direct addition of both HMM- and LMM-poly I:C to the cultures of primary macrophages or a neuroplastoma cell line could activate TLR3. However, the transfection of poly I:C was necessary to induce TLR3 activation in other cell types studied. In all the cell lines tested, the efficiency of TLR3 activation by HMM-poly I:C was significantly higher than that by LMM-poly I:C. These observations indicate the importance and necessity of developing effective TLR3 ligands for antiviral therapy.

Tonsil-derived mesenchymal stromal cells produce CXCR2-binding chemokines and acquire follicular dendritic cell-like phenotypes under TLR3 stimulation

“…2B). In contrast with a previous report on the efficacy of TLR3 activation by HMW-poly I:C, which was significantly higher than that by TLR3 (LMW) [17], prominent differences were not observed between TLR3 and TLR3 (LMW) in T-MSCs in CCR6 expression.…”

Induction of interferon-induced transmembrane protein 3 gene expression by lipopolysaccharide in astrocytes

“…It is known that TLR3, RIG-I, and MDA5 recognize the dsRNA analog polyI:C differently depending on its length (Kato et al, 2008;de Rivero Vaccari et al, 2012;Zhou et al, 2013). We have recently shown that TLR3, RIG-I, and MDA5 are up-regulated in astrocytes when activated with polyI:C, which may behave like a long dsRNA under our experimental conditions (Ibi et al, 2013).…”

Stimulation of the RIG-I/MAVS Pathway by Polyinosinic:Polycytidylic Acid Upregulates IFN-β in Airway Epithelial Cells with Minimal Costimulation of IL-8

“…Notably, several commercial formulations of poly(I:C) exist with potentially different effects on immune cells (56,57). The availability of various formulations of poly(I:C) may be advantageous, because its molecular size and chemical modifications play an important fine-tuning role in stimulating innate cell responses and may allow for a greater versatility in different pathologic conditions.…”