TLR3 is essential for the induction of protective immunity against Punta Toro virus infection by the double-stranded RNA (dsRNA), poly(I:C12U), but not poly(I:C):: Differential, recognition of synthetic dsRNA molecules
TLR3 is essential for the induction of protective immunity against Punta Toro virus infection by the double-stranded RNA (dsRNA), poly(I:C12U), but not poly(I:C):: Differential, recognition of synthetic dsRNA molecules
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DOI：
10.4049/jimmunol.178.8.5200
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发表时间：
2007-04-15
影响因子：
4.4
通讯作者：
Sidwell, Robert W.
中科院分区：
文献类型：
--
作者：
Gowen, Brian B.;Wong, Min-Hui;Sidwell, Robert W.
在RNA病毒感染后，通常会产生dsRNA中间体。这些病毒病原体相关的分子模式可以被越来越多的宿主细胞胞质蛋白和TLR 3所感知，这有助于诱导抗病毒防御。最近的证据表明，黑色素瘤分化相关基因-5是暴露于dsRNA类似物poly（I：C）后介导IFN产生的主要宿主组分。我们以前曾报道过，小鼠中的蓬塔托罗病毒（PTV）感染对poly（I：C12 U）治疗非常敏感，poly（I：C12 U）是一种dsRNA类似物，具有上级安全性，同时保持了亲本poly（I：C）在诱导先天免疫应答中的有益活性。其施用后介导保护性免疫的确切宿主因子仍有待阐明。为了评估TLR 3在该过程中的作用，使用缺乏受体的小鼠来研究治疗后保护性免疫、I型IFN和IL-6的诱导。与野生型小鼠不同，缺乏TLR 3的小鼠在poly（I：C12 U）治疗后不能抵抗PTV感染，并且不能产生IFN-α、IFN-β和IL-6。相比之下，聚（I：C）治疗显着保护TLR 3（-/-）小鼠从致命的挑战，尽管在细胞因子诱导的一些缺陷。没有迹象表明缺乏保护是由于TLR 3缺陷小鼠抵抗感染的能力降低，因为它们没有发现对PTV更敏感。我们的结论是。TLR 3是必不可少的诱导的抗病毒活性引起的聚（I：C12 U），这似乎不被识别的胞质传感器的聚（I：C），黑色素瘤分化相关基因-5。
In the wake of RNA virus infections, dsRNA intermediates are often generated. These viral pathogen-associated molecular patterns can be sensed by a growing number of host cell cytosolic proteins and TLR3, which contribute to the induction of antiviral defenses. Recent evidence indicates that melanoma differentiation-associated gene-5 is the prominent host component mediating IFN production after exposure to the dsRNA analog, poly(I:C). We have previously reported that Punta Toro virus (PTV) infection in mice is exquisitely sensitive to treatment with poly(I:C12U), a dsRNA analog that has a superior safety profile while maintaining the beneficial activity of the parental poly(I:C) in the induction of innate immune responses. The precise host factor(s) mediating protective immunity following its administration remain to be elucidated. To assess the role of TLR3 in this process, mice lacking the receptor were used to investigate the induction of protective immunity, type I IFNs, and IL-6 following treatment. Unlike wild-type mice, those lacking TLR3 were not protected against PTV infection following poly(I:C12U) therapy and failed to produce IFN-alpha, IFN-beta, and IL-6. In contrast, poly(I:C) treatment significantly protected TLR3(-/-) mice from lethal challenge despite some deficiencies in cytokine induction. There was no indication that the lack of protection was due to the fact that TLR3-deficient mice had a reduced capacity to fight infection because they were not found to be more susceptible to PTV. We conclude that. TLR3 is essential to the induction of antiviral activity elicited by poly(I:C12U), which does not appear to be recognized by the cytosolic sensor of poly(I:C), melanoma differentiation-associated gene-5.