University of Tunis El Manar, Faculty of Sciences of Tunis, Laboratory of Mycology, Pathologies and Biomarkers: LR16ES05, 2092, Tunisia.
Charles Nicolle Hospital, Hepato-Gastro-Enterology Department, Tunis, Tunisia.
Cytokine. 2017 Nov;99:297-304. doi: 10.1016/j.cyto.2017.08.010. Epub 2017 Aug 18.
TLRs are one of the most studied families of pathogen recognition receptors (PRRs) and play a pivotal role during HCV infection. The binding of ligands to TLRs on antigen presenting cells (APCs) leads to secretion of inflammatory cytokines, such as IL6, and induction of the acquired immunity response. Therefore, it has become necessarily to harness the TLRs properties' on therapeutically tools to enhance the HCV treatment response. Herein, we investigated the association between TLR3, TLR4 variants and nine IL-6 polymorphisms, and response to anti-viral treatment during HCV infection.
Study subjects comprised 120 patients infected with HCV-1b and treated with Peg-IFN/RBV. Genotyping of nine IL-6 variants were done by real -time PCR and genotyping of TLRs polymorphisms were done by RFLP-PCR.
High frequency of TLR3 rs3775290 C/C genotype and TLR4 rs4986790 A/A genotype were noticed among patients with sustained viral response compared to Non-responder patients. The genetic association of TLR3 and TLR4 variants was evidenced by the improvement in the kinetics of viral load decline, with superiority of TLR3 compared to TLR4. Among, nine polymorphisms studied on IL-6 only rs1800796, rs2069845 and rs1880242 were associated with sustained viral response. Our study reports also that the common favourable IL-28B variant is essential for TLR-activated antiviral protection.
TLR3 and TLR4 are involved in the pathogenesis of viral infections. TLR3 may be better suited than TLR4 to activate anti-viral program. Moreover, we propose that the Th2 cytokine, IL-6, constitutes a determinant of the outcome of therapy in HCV patients.
TLR 是最受研究的病原体识别受体 (PRR) 家族之一，在 HCV 感染中发挥关键作用。配体与抗原呈递细胞 (APC) 上的 TLR 结合会导致炎症细胞因子（如 IL6）的分泌，并诱导获得性免疫反应。因此，利用 TLR 特性来开发治疗工具以增强 HCV 治疗反应变得非常必要。在此，我们研究了 TLR3、TLR4 变体与 9 个 IL-6 多态性之间的关联，以及它们与 HCV 感染期间抗病毒治疗反应的关系。
研究对象包括 120 例感染 HCV-1b 并接受 Peg-IFN/RBV 治疗的患者。通过实时 PCR 对 9 个 IL-6 变体的基因分型，通过 RFLP-PCR 对 TLRs 多态性的基因分型。
与无应答患者相比，持续病毒应答患者中 TLR3 rs3775290 C/C 基因型和 TLR4 rs4986790 A/A 基因型的高频出现。TLR3 和 TLR4 变体的遗传关联通过病毒载量下降动力学的改善得到证实，TLR3 的优势优于 TLR4。在研究的 9 个 IL-6 多态性中，只有 rs1800796、rs2069845 和 rs1880242 与持续病毒应答相关。我们的研究还报告称，常见的有利 IL-28B 变体对于 TLR 激活的抗病毒保护至关重要。
TLR3 和 TLR4 参与病毒感染的发病机制。TLR3 可能比 TLR4 更适合激活抗病毒程序。此外，我们提出 Th2 细胞因子 IL-6 是 HCV 患者治疗结果的决定因素。
