Center for Translational Ocular Immunology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA; Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA; Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Cell Rep. 2020 Sep 1;32(9):108099. doi: 10.1016/j.celrep.2020.108099.
The presence and potential functions of resident plasmacytoid dendritic cells (pDCs) in peripheral tissues is unclear. We report that pDCs constitutively populate naïve corneas and are increased during sterile injuries or acute herpes simplex virus 1 (HSV-1) keratitis. Their local depletion leads to severe clinical disease, nerve loss, viral dissemination to the trigeminal ganglion and draining lymph nodes, and mortality, while their local adoptive transfer limits disease. pDCs are the main source of HSV-1-induced IFN-α in the corneal stroma through TLR9, and they prevent re-programming of regulatory T cells (Tregs) to effector ex-Tregs. Clinical signs of infection are observed in pDC-depleted corneas, but not in pDC-sufficient corneas, following low-dose HSV-1 inoculation, suggesting their critical role in corneal antiviral immunity. Our findings demonstrate a vital role for corneal pDCs in the control of local viral infections.
驻留浆细胞样树突状细胞（pDCs）在外周组织中的存在和潜在功能尚不清楚。我们报告称，pDCs 持续存在于幼稚角膜中，并在无菌损伤或单纯疱疹病毒 1（HSV-1）角膜炎时增加。它们的局部耗竭会导致严重的临床疾病、神经损失、病毒向三叉神经节和引流淋巴结的传播以及死亡率，而它们的局部过继转移则限制了疾病的发生。pDCs 通过 TLR9 成为角膜基质中 HSV-1 诱导 IFN-α的主要来源，并防止调节性 T 细胞（Tregs）重新编程为效应 ex-Tregs。在低剂量 HSV-1 接种后，pDC 耗竭的角膜中会观察到感染的临床体征，但 pDC 充足的角膜中不会观察到，这表明它们在角膜抗病毒免疫中具有关键作用。我们的研究结果表明，角膜 pDCs 在控制局部病毒感染方面发挥着重要作用。
