Interferon regulatory factor-1 (IRF-1) shapes both innate and CD8(+) T cell immune responses against West Nile virus infection.
Interferon regulatory factor-1 (IRF-1) shapes both innate and CD8(+) T cell immune responses against West Nile virus infection.
复制标题
DOI：
10.1371/journal.ppat.1002230
复制
发表时间：
2011-09
期刊：
影响因子：
6.7
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Brien JD;Daffis S;Lazear HM;Cho H;Suthar MS;Gale M Jr;Diamond MS
干扰素调节因子（IRF）-1是一种免疫调节转录因子，在病原体识别受体信号传导的下游发挥作用，并被认为是I型干扰素（IFN）-αβ表达和对病毒感染的免疫应答的调节因子。然而，IRF-1的这种作用仍然存在争议，因为在IRF-1 -/-小鼠中尚未观察到I型IFN应答的改变。为了评估IRF-1和免疫调节的关系，我们评估了西尼罗河病毒（WNV）在IRF-1 -/-细胞和小鼠中的感染性和宿主反应。IRF-1 -/-小鼠对WNV感染非常脆弱，其外周组织中的病毒复制增强，并迅速传播到中枢神经系统。离体分析揭示了细胞类型特异性抗病毒作用，因为IRF-1 -/-巨噬细胞支持增强的WNV复制，但IRF-1 -/-成纤维细胞中的感染未改变。IRF-1对CD 8 + T细胞扩增也有独立和矛盾的作用。尽管如前所述，在未经处理的动物中观察到明显较少的CD 8 + T细胞，但值得注意的是，IRF-1 -/-小鼠迅速扩增了其WNV特异性溶细胞性CD 8 + T细胞库。连续转移和体外增殖实验确立了IRF-1对CD 8 + T细胞扩增的细胞内在和细胞外在效应。因此，IRF-1通过调节先天性抗病毒效应分子的表达同时形成抗原特异性CD 8 + T细胞应答来限制WNV感染。干扰素调节因子（IRF）-1是一种转录因子，参与免疫调节和诱导I型IFN基因表达。为了更好地了解IRF-1对抗病毒免疫的作用，我们用西尼罗河病毒（WNV）感染缺乏IRF-1的细胞和小鼠，这是一种脑炎黄病毒。IRF-1 -/-小鼠一致易受WNV感染，病毒复制增强，并迅速传播到大脑和脊髓中。细胞培养研究揭示了细胞类型特异性抗病毒作用，因为IRF-1 -/-巨噬细胞而不是成纤维细胞支持增强的WNV复制。IRF-1对CD 8 + T细胞应答也有独立作用。尽管在未处理动物中观察到较少的CD 8 + T细胞，但WNV特异性CD 8 + T细胞在IRF-1 -/-小鼠中迅速扩增，并保留清除感染的能力。总的来说，我们的研究确定了IRF-1在限制WNV发病机制和调节保护性CD 8 + T细胞应答中的独立作用。
Interferon regulatory factor (IRF)-1 is an immunomodulatory transcription factor that functions downstream of pathogen recognition receptor signaling and has been implicated as a regulator of type I interferon (IFN)-αβ expression and the immune response to virus infections. However, this role for IRF-1 remains controversial because altered type I IFN responses have not been systemically observed in IRF-1 -/- mice. To evaluate the relationship of IRF-1 and immune regulation, we assessed West Nile virus (WNV) infectivity and the host response in IRF-1 -/- cells and mice. IRF-1 -/- mice were highly vulnerable to WNV infection with enhanced viral replication in peripheral tissues and rapid dissemination into the central nervous system. Ex vivo analysis revealed a cell-type specific antiviral role as IRF-1 -/- macrophages supported enhanced WNV replication but infection was unaltered in IRF-1 -/- fibroblasts. IRF-1 also had an independent and paradoxical effect on CD8+ T cell expansion. Although markedly fewer CD8+ T cells were observed in naïve animals as described previously, remarkably, IRF-1 -/- mice rapidly expanded their pool of WNV-specific cytolytic CD8+ T cells. Adoptive transfer and in vitro proliferation experiments established both cell-intrinsic and cell-extrinsic effects of IRF-1 on the expansion of CD8+ T cells. Thus, IRF-1 restricts WNV infection by modulating the expression of innate antiviral effector molecules while shaping the antigen-specific CD8+ T cell response. Interferon regulatory factor (IRF)-1 is a transcription factor that has been implicated in immune regulation and induction of type I IFN gene expression. To better understand the contribution of IRF-1 to antiviral immunity, we infected cells and mice lacking IRF-1 with West Nile virus (WNV), an encephalitic flavivirus. IRF-1 -/- mice were uniformly vulnerable to WNV infection with enhanced viral replication and rapid dissemination into the brain and spinal cord. Studies in cell culture revealed a cell-type specific antiviral role as IRF-1 -/- macrophages but not fibroblasts supported enhanced WNV replication. IRF-1 also had an independent effect on CD8+ T cell responses. Although fewer CD8+ T cells were observed in naïve animals, WNV-specific CD8+ T cells rapidly expanded in IRF-1 -/- mice and retained the capacity to clear infection. Collectively, our studies define independent roles for IRF-1 in restricting WNV pathogenesis and modulating the protective CD8+ T cell response.
登录
查看更多内容
影响因子：
6.7
作者：
DeWitte-Orr SJ;Collins SE;Bauer CM;Bowdish DM;Mossman KL
通讯作者：
Mossman KL
影响因子：
2.3
作者：
Ank, Nina;West, Hans;Paludan, Soren R.
通讯作者：
Paludan, Soren R.
影响因子：
4.4
作者：
Feng, CG;Watanabe, S;Asano, Y
通讯作者：
Asano, Y
病毒mRNA帽的2'-O甲基化通过IFIT家族成员逃避了宿主的限制。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
30.5
作者：
Kano, Shin-ichi;Sato, Kojiro;Taniguchi, Tadatsugu
通讯作者：
Taniguchi, Tadatsugu