角膜树突状细胞在单纯疱疹性角膜炎中的双重作用:局部抑制角膜损伤并促进全身病毒传播。
A Dual Role for Corneal Dendritic Cells in Herpes Simplex Keratitis: Local Suppression of Corneal Damage and Promotion of Systemic Viral Dissemination.
作者信息
Hu Kai, Harris Deshea L, Yamaguchi Takefumi, von Andrian Ulrich H, Hamrah Pedram
机构信息
Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America; Cornea Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America; Immune Disease Institute, Program in Cellular and Molecular Medicine at Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America.
Schepens Eye Research Institute, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America; Immune Disease Institute, Program in Cellular and Molecular Medicine at Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
出版信息
PLoS One. 2015 Sep 2;10(9):e0137123. doi: 10.1371/journal.pone.0137123. eCollection 2015.
The cornea is the shield to the foreign world and thus, a primary site for peripheral infections. However, transparency and vision are incompatible with inflammation and scarring that may result from infections. Thus, the cornea is required to perform a delicate balance between fighting infections and preserving vision. To date, little is known about the specific role of antigen-presenting cells in viral keratitis. In this study, utilizing an established murine model of primary acute herpes simplex virus (HSV)-1 keratitis, we demonstrate that primary HSV keratitis results in increased conventional dendritic cells (cDCs) and macrophages within 24 hours after infection. Local depletion of cDCs in CD11c-DTR mice by subconjuntival diphtheria toxin injections, led to increased viral proliferation, and influx of inflammatory cells, resulting in increased scarring and clinical keratitis. In addition, while HSV infection resulted in significant corneal nerve destruction, local depletion of cDCs resulted in a much more severe loss of corneal nerves. Further, local cDC depletion resulted in decreased corneal nerve infection, and subsequently decreased and delayed systemic viral transmission in the trigeminal ganglion and draining lymph node, resulting in decreased mortality of mice. In contrast, sham depletion or depletion of macrophages through local injection of clodronate liposomes had neither a significant impact on the cornea, nor an effect on systemic viral transmission. In conclusion, we demonstrate that corneal cDCs may play a primary role in local corneal defense during viral keratitis and preserve vision, at the cost of inducing systemic viral dissemination, leading to increased mortality.
角膜是抵御外界的屏障,因此是周围感染的主要部位。然而,透明度和视力与感染可能导致的炎症和瘢痕形成不相容。因此,角膜需要在对抗感染和保护视力之间保持微妙的平衡。迄今为止,关于抗原呈递细胞在病毒性角膜炎中的具体作用知之甚少。在本研究中,利用已建立的原发性急性单纯疱疹病毒(HSV)-1角膜炎小鼠模型,我们证明原发性HSV角膜炎在感染后24小时内会导致传统树突状细胞(cDCs)和巨噬细胞增加。通过结膜下注射白喉毒素使CD11c-DTR小鼠体内的cDCs局部耗竭,导致病毒增殖增加和炎性细胞流入,从而导致瘢痕形成增加和临床角膜炎加重。此外,虽然HSV感染导致角膜神经严重受损,但cDCs的局部耗竭导致角膜神经损失更为严重。此外,局部cDC耗竭导致角膜神经感染减少,随后三叉神经节和引流淋巴结中的全身病毒传播减少并延迟,从而降低了小鼠的死亡率。相比之下,假耗竭或通过局部注射氯膦酸脂质体耗竭巨噬细胞对角膜均无显著影响,对全身病毒传播也无作用。总之,我们证明角膜cDCs在病毒性角膜炎期间可能在局部角膜防御中起主要作用并保护视力,但代价是诱导全身病毒传播,导致死亡率增加。
相似文献
Invest Ophthalmol Vis Sci. 2000-5
Invest Ophthalmol Vis Sci. 2022-2-1
Prog Retin Eye Res. 2006-7
引用本文的文献
Clin Microbiol Rev. 2024-9-12
Biomedicines. 2022-8-16
Virulence. 2021-12
本文引用的文献
Invest Ophthalmol Vis Sci. 2014-4-15
Invest Ophthalmol Vis Sci. 2012-5-31
Invest Ophthalmol Vis Sci. 2012-2-21