Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1beta production.
Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1beta production.
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DOI：
10.1186/s13104-018-3975-4
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发表时间：
2018-12-04
影响因子：
1.8
通讯作者：
Abdul-Careem, Mohamed Faizal
中科院分区：
文献类型：
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作者：
Abdul-Cader, Mohamed Sarjoon;De Silva Senapathi, Upasama;Abdul-Careem, Mohamed Faizal
目的：单链核糖核酸（ssRNA）与toll样受体（TLR）7结合，导致免疫细胞的募集和促炎细胞因子的产生，这已在哺乳动物中显示。在鸡中，ssRNA已被证明可以引发针对传染性法氏囊病病毒感染的抗病毒应答。本研究的目的是确定禽巨噬细胞中激活的TLR 7信号通路下游的促炎介质及其在抗禽流感病毒（AIV）感染的抗病毒应答中的作用。在这项研究中，首先，我们用ssRNA的类似物瑞喹莫特刺激禽类巨噬细胞，并发现ssRNA能够增加禽类巨噬细胞中一氧化氮（NO）和白细胞介素（IL-1 β）的产生。第二，我们观察到当用ssRNA刺激禽巨噬细胞时，它引起抗AIV的抗病毒应答。最后，我们证明，当我们用IL-1受体拮抗剂（IL-1 Ra）阻断IL-1 β反应和用诱导型一氧化氮合酶（iNOS）的选择性抑制剂N-（[3-（氨甲基）苯基]甲基）乙脒盐酸盐（1400 W）阻断NO产生时，抗AIV的抗病毒反应可归因于IL-1 β的产生，而不是NO的产生。这项研究为ssRNA介导的抗病毒反应机制提供了新的见解，特别是针对AIV感染。
OBJECTIVE: Single stranded ribonucleic acid (ssRNA) binds to toll-like receptor (TLR)7 leading to recruitment of immune cells and production of pro-inflammatory cytokines, which has been shown in mammals. In chickens, ssRNA has been shown to elicit antiviral response against infectious bursal disease virus infection. The objectives of this study were to determine the pro-inflammatory mediators that are activated downstream of TLR7 signaling pathway in avian macrophages and their roles in antiviral response against avian influenza virus (AIV) infection.RESULTS: In this study, first, we stimulated avian macrophages with the analog of ssRNA, resiquimod, and found that the ssRNA was capable of increasing nitric oxide (NO) and interleukin (IL-1beta) production in avian macrophages. Second, we observed when the avian macrophages were stimulated with ssRNA, it elicits an antiviral response against AIV. Finally, we demonstrated that when we blocked the IL-1beta response using IL-1 receptor antagonist (IL-1Ra) and the NO production using a selective inhibitor of inducible nitric oxide synthase (iNOS), N-([3-(aminomethyl)phenyl]methyl)ethanimidamide dihydrochloride (1400W), the antiviral response against AIV is attributable to IL-1beta production and not to the NO production. This study provides insights into the mechanisms of antiviral response mediated by ssRNA, particularly against AIV infection.