TLR3 activation efficiency by high or low molecular mass poly I:C. Issue 2 (April 2013)

• Record Type: Journal Article
• Authors: Zhou, Yu; Guo, Ming; Wang, Xu; Li, Jielang; Wang, Yizhong; Ye, Li; Dai, Ming; Zhou, Li; Persidsky, Yuri; Ho, Wenzhe
• Is Part Of: Innate immunity. Volume 19:Issue 2(2013)
• Page Start: 184
• Page End: 192
• Publication Date: 2013-04
• Subjects: TLR3 -- poly I:C -- type I IFN -- type III IFN -- LyoVec; Natural immunity -- Periodicals; Endotoxins -- Periodicals; 616.07905
• DOI: 10.1177/1753425912459975
• Languages: English
• ISSNs: 1753-4259

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.