The mechanism of recognition of the foot-and-mouth disease virus (FMDV) by host innate immune cells is not well-understood. In this study, we first found that binary ethylenimine inactivated-FMDV (BEI-FMDV) with structurally intact capsid activated TLR2, but not other TLRs, and this specific activation was blocked by anti-TLR2 Abs or knockout of TLR2. BEI-FMDV activated NF-κB to induce cytokines, notably interferon-β and IL-6, in a TLR2 and MyD88-dependent manner. Coexpression of TLR6 and CD14 showed additive effects on BEI-FMDV/TLR2-mediated activation of NF-κB. Further studies demonstrated that recombinant capsid proteins rVP1 and rVP3 of FMDV but not rVP0 bound directly with CD14 and TLR2. The rVP1- and rVP3-mediated activation of TLR2 and NF-κB were enhanced by the coexpression of TLR1 or TLR6. Immunoprecipitation of either rVP1 or rVP3 with mouse macrophage cell extracts revealed that rVP1 or rVP3 associated with TLR2, CD14 and TLR6 suggesting that rVP1 and rVP3 interact with CD14, TLR2/TLR1, and TLR2/TLR6 heterodimer. Additional study confirmed that rVP1 and rVP3 interacted with the swine TLR2 signaling pathway to induce IL-6 in swine macrophages. Our results identify VP1 and VP3 of FMDV as novel TLR agonists whose recognition by CD14, TLR2/TLR1, and TLR2/TLR6 of host innate immune cells is critical for the induction of cytokine production.

中文翻译：

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口蹄疫病毒的衣壳蛋白与TLR2和CD14相互作用，诱导细胞因子的产生。

宿主先天性免疫细胞识别口蹄疫病毒（FMDV）的机制尚不清楚。在这项研究中，我们首先发现具有结构完整的衣壳的二甲基亚乙基亚胺灭活的FMDV（BEI-FMDV）激活了TLR2，但没有其他TLRs激活，这种特异性激活被抗TLR2 Abs或TLR2的敲除所阻断。BEI-FMDV以TLR2和MyD88依赖性方式激活NF-κB以诱导细胞因子，特别是干扰素-β和IL-6。TLR6和CD14的共表达对BEI-FMDV / TLR2介导的NF-κB活化具有累加作用。进一步的研究表明，FMDV的重组衣壳蛋白rVP1和rVP3但rVP0不直接与CD14和TLR2结合。TLR1或TLR6的共表达增强了rVP1和rVP3介导的TLR2和NF-κB的激活。用小鼠巨噬细胞提取物对rVP1或rVP3进行免疫沉淀显示，rVP1或rVP3与TLR2，CD14和TLR6相关，提示rVP1和rVP3与CD14，TLR2 / TLR1和TLR2 / TLR6异二聚体相互作用。进一步的研究证实，rVP1和rVP3与猪TLR2信号通路相互作用，在猪巨噬细胞中诱导IL-6。我们的结果确定FMDV的VP1和VP3是新型TLR激动剂，其对宿主先天性免疫细胞的CD14，TLR2 / TLR1和TLR2 / TLR6的识别对于诱导细胞因子的产生至关重要。进一步的研究证实，rVP1和rVP3与猪TLR2信号通路相互作用，在猪巨噬细胞中诱导IL-6。我们的结果确定FMDV的VP1和VP3是新型TLR激动剂，其对宿主先天性免疫细胞的CD14，TLR2 / TLR1和TLR2 / TLR6的识别对于诱导细胞因子的产生至关重要。进一步的研究证实，rVP1和rVP3与猪TLR2信号通路相互作用，在猪巨噬细胞中诱导IL-6。我们的结果确定FMDV的VP1和VP3是新型TLR激动剂，其对宿主先天性免疫细胞的CD14，TLR2 / TLR1和TLR2 / TLR6的识别对于诱导细胞因子的产生至关重要。