Division of Applied Medicine, Section of Immunity, Infection and Inflammation (Ocular Immunology), Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Beijing, China.
Front Immunol. 2022 Nov 28;13:1054260. doi: 10.3389/fimmu.2022.1054260. eCollection 2022.
Herpes stromal keratitis (HSK) is a blinding corneal disease caused by herpes simplex virus-1 (HSV-1), a common pathogen infecting most of the world's population. Inflammation in HSK is chemokine-dependent, particularly CXCL10 and less so the CC chemokines. The atypical chemokine receptor-2 (ACKR2) is a decoy receptor predominantly for pro-inflammatory CC chemokines, which regulates the inflammatory response by scavenging inflammatory chemokines thereby modulating leukocyte infiltration. Deletion of ACKR2 exacerbates and delays the resolution of the inflammatory response in most models. ACKR2 also regulates lymphangiogenesis and mammary duct development through the recruitment of tissue-remodeling macrophages. Here, we demonstrate a dose-dependent upregulation of ACKR2 during corneal HSV-1 infection. At an HSV inoculum dose of 5.4 x 10 pfu, but not at higher dose, ACKR2 deficient mice showed prolonged clinical signs of HSK, increased infiltration of leukocytes and persistent corneal neovascularization. Viral clearance and T cell activation were similar in ACKR2 and wild type mice, despite a transient diminished expression of CD40 and CD86 in dendritic cells. The data suggest that ACKR2 fine-tunes the inflammatory response and the level of neovascularization in the HSK.
单纯疱疹病毒性角膜炎（HSK）是一种致盲性角膜疾病，由单纯疱疹病毒 1 型（HSV-1）引起，该病毒是一种常见病原体，感染了世界上大多数人口。HSK 的炎症依赖趋化因子，特别是 CXCL10，而对 CC 趋化因子的依赖性较小。非典型趋化因子受体 2（ACKR2）是一种主要针对促炎 CC 趋化因子的诱饵受体，通过清除炎症趋化因子来调节炎症反应，从而调节白细胞浸润。ACKR2 的缺失会加剧并延迟大多数模型中炎症反应的消退。ACKR2 还通过招募组织重塑巨噬细胞来调节淋巴管生成和乳腺导管发育。在这里，我们证明了 ACKR2 在角膜 HSV-1 感染过程中呈剂量依赖性上调。在 HSV 接种剂量为 5.4 x 10 pfu 时，但在更高剂量时，ACKR2 缺陷型小鼠表现出 HSK 临床症状延长、白细胞浸润增加和持续性角膜新生血管形成。尽管树突状细胞中 CD40 和 CD86 的表达短暂降低，但 ACKR2 和野生型小鼠中的病毒清除和 T 细胞活化相似。数据表明，ACKR2 可微调 HSK 中的炎症反应和新生血管化水平。
