Binding mode of CpG oligodeoxynucleotides to nanoparticles regulates bifurcated cytokine induction via Toll-like receptor 9

CpG 寡脱氧核苷酸与纳米粒子的结合模式通过 Toll 样受体 9 调节分叉细胞因子诱导

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作者:Shanmugavel Chinnathambi, Song Chen, Singaravelu Ganesan, Nobutaka Hanagata

Abstract

The interaction of cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) with Toll-like receptor 9 (TLR9) activates the immune system. Multimeric class A CpG ODNs induce interferon-α (IFN-α) and, to a lesser extent, interleukin-6. By contrast, monomeric class B CpG ODNs induce interleukin-6 but not IFN-α. This difference suggests that the multimerization of CpG ODN molecules is a key factor in IFN-α induction. We multimerized class B CpG ODN2006x3-PD molecules that consist entirely of a phosphodiester backbone onto quantum dot silicon nanoparticles with various binding modes. Herein, we present the binding mode-dependent bifurcation of cytokine induction and discuss its possible mechanism of CpG ODN and TLR9 interaction. Our discoveries also suggest that nanoparticles play roles in not only delivery of CpG ODNs but also control of CpG ODN activity.

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