Adaptive and Innate Transforming Growth Factor β Signaling Impact Herpes Simplex Virus 1 Latency and Reactivation
Adaptive and Innate Transforming Growth Factor β Signaling Impact Herpes Simplex Virus 1 Latency and Reactivation
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DOI：
10.1128/jvi.00678-11
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发表时间：
2011-11-01
影响因子：
5.4
通讯作者：
Ghiasi, Homayon
中科院分区：
文献类型：
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作者：
Allen, Sariah J.;Mott, Kevin R.;Ghiasi, Homayon
先天性免疫和获得性免疫通过对抗单纯疱疹病毒1型(HSV-1)感染发挥着重要的保护作用。转化生长因子-β是天然免疫反应和获得性免疫反应的关键负性细胞因子调节因子。然而，目前尚不清楚两个免疫间隔中的转化生长因子-β信号是否会影响HSV-1的复制和潜伏期。我们采用遗传方法来解决这些问题，通过感染两种不同的显性阴性的转化生长因子-β受体II型转基因小鼠品系。这些小鼠在T细胞或天然细胞中有特定的转化生长因子-β信号阻断。小鼠眼部感染HSV-1，以评估在急性和潜伏感染期间限制的先天或适应性的转化生长因子-β信号的影响。限制固有细胞，而不是T细胞转化生长因子-β信号，减少了感染小鼠眼睛中的病毒复制。另一方面，阻断先天细胞或T细胞中的转化生长因子-β信号导致感染小鼠三叉神经节潜伏期缩短。此外，抑制T细胞中的转化生长因子-β信号可减少小鼠原发单纯疱疹病毒1型感染时角膜和三叉神经节中的细胞溶解和白细胞浸润。这些发现强烈表明，通常起抑制免疫反应作用的转化生长因子-β信号会导致HSV-1潜伏期延长。
Innate and adaptive immunity play important protective roles by combating herpes simplex virus 1 (HSV-1) infection. Transforming growth factor beta (TGF-beta) is a key negative cytokine regulator of both innate and adaptive immune responses. Yet, it is unknown whether TGF-beta signaling in either immune compartment impacts HSV-1 replication and latency. We undertook genetic approaches to address these issues by infecting two different dominant negative TGF-beta receptor type II transgenic mouse lines. These mice have specific TGF-beta signaling blockades in either T cells or innate cells. Mice were ocularly infected with HSV-1 to evaluate the effects of restricted innate or adaptive TGF-beta signaling during acute and latent infections. Limiting innate cell but not T cell TGF-beta signaling reduced virus replication in the eyes of infected mice. On the other hand, blocking TGF-beta signaling in either innate cells or T cells resulted in decreased latency in the trigeminal ganglia of infected mice. Furthermore, inhibiting TGF-beta signaling in T cells reduced cell lysis and leukocyte infiltration in corneas and trigeminal ganglia during primary HSV-1 infection of mice. These findings strongly suggest that TGF-beta signaling, which generally functions to dampen immune responses, results in increased HSV-1 latency.