Division of Infectious Diseases and.
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
JCI Insight. 2020 Mar 12;5(5):134258. doi: 10.1172/jci.insight.134258.
Herpes simplex virus-2 (HSV-2) and HSV-1 both can cause genital herpes, a chronic infection that establishes a latent reservoir in the nervous system. Clinically, the recurrence frequency of HSV-1 genital herpes is considerably less than HSV-2 genital herpes, which correlates with reduced neuronal infection. The factors dictating the disparate outcomes of HSV-1 and HSV-2 genital herpes are unclear. In this study, we show that vaginal infection of mice with HSV-1 leads to the rapid appearance of mature DCs in the draining lymph node, which is dependent on an early burst of NK cell-mediated IFN-γ production in the vagina that occurs after HSV-1 infection but not HSV-2 infection. Rapid DC maturation after HSV-1 infection, but not HSV-2 infection, correlates with the accelerated generation of a neuroprotective T cell response and early accumulation of IFN-γ-producing T cells at the site of infection. Depletion of T cells or loss of IFN-γ receptor (IFN-γR) expression in sensory neurons both lead to a marked loss of neuroprotection only during HSV-1, recapitulating a prominent feature of HSV-2 infection. Our experiments reveal key differences in host control of neuronal HSV-1 and HSV-2 infection after genital exposure of mice, and they define parameters of a successful immune response against genital herpes.
单纯疱疹病毒-2（HSV-2）和 HSV-1 均可引起生殖器疱疹，这是一种在神经系统中建立潜伏储存库的慢性感染。临床上，HSV-1 生殖器疱疹的复发频率明显低于 HSV-2 生殖器疱疹，这与神经元感染减少有关。决定 HSV-1 和 HSV-2 生殖器疱疹不同结局的因素尚不清楚。在这项研究中，我们表明，HSV-1 阴道感染可导致引流淋巴结中成熟 DC 的快速出现，这依赖于 HSV-1 感染后而非 HSV-2 感染后阴道中 NK 细胞介导的 IFN-γ产生的早期爆发。HSV-1 感染后迅速的 DC 成熟，但 HSV-2 感染后没有，与神经保护性 T 细胞反应的加速生成以及感染部位 IFN-γ产生 T 细胞的早期积累相关。在 HSV-1 感染期间，T 细胞耗竭或感觉神经元中 IFN-γ 受体（IFN-γR）表达缺失都会导致明显的神经保护缺失，这再现了 HSV-2 感染的一个显著特征。我们的实验揭示了小鼠生殖道暴露后宿主对神经元 HSV-1 和 HSV-2 感染的控制的关键差异，并定义了针对生殖器疱疹的成功免疫反应的参数。
