miR-155 Suppresses Bacterial Clearance in Pseudomonas aeruginosa-Induced Keratitis by Targeting Rheb
miR-155 Suppresses Bacterial Clearance in Pseudomonas aeruginosa-Induced Keratitis by Targeting Rheb
复制标题
miR-155 通过靶向 Rheb 抑制铜绿假单胞菌引起的角膜炎的细菌清除
DOI：
10.1093/infdis/jiu002
复制
发表时间：
2014-07-01
影响因子：
6.4
通讯作者：
Huang, Xi
中科院分区：
文献类型：
--
作者：
Yang, Kun;Wu, Minhao;Huang, Xi
miR-155 （microRNA-155）是调节宿主炎症反应的重要非编码RNA。然而，其在眼部感染中的调节作用尚不清楚。我们的研究首次探索了miR-155在铜绿假单胞菌诱导的角膜炎中的功能，角膜炎是最常见的视力威胁眼病之一。我们发现，在P. aeruginosa感染后，miR-155在人和小鼠角膜中的表达增强，并且主要在巨噬细胞中表达，而不表达中性粒细胞。体内研究表明，miR-155敲除小鼠对P. aeruginosa角膜炎表现出更强的抗性，诱导型一氧化氮合酶水平更高，细菌负担更低。更重要的是，体外数据表明，miR-155通过靶向Rheb（大脑中富集的Ras同源物）抑制巨噬细胞介导的细菌吞噬和P. aeruginosa的细胞内杀伤。据我们所知，这是第一个探讨miR-155在细菌性角膜炎中的作用的研究，这可能为P. aeruginosa角膜炎等感染性疾病的临床治疗提供一个有希望的靶点。
miR-155 (microRNA-155) is an important noncoding RNA in regulating host inflammatory responses. However, its regulatory role in ocular infection remains unclear. Our study first explored the function of miR-155 in Pseudomonas aeruginosa-induced keratitis, one of the most common sight-threatening ocular diseases. We found that miR-155 expression was enhanced in human and mouse corneas after P. aeruginosa infection and was mainly expressed in macrophages but not neutrophils. In vivo studies demonstrated that miR-155 knockout mice displayed more resistance to P. aeruginosa keratitis, with a higher inducible nitric oxide synthase level and a lower bacterial burden. More importantly, in vitro data indicated that miR-155 suppressed the macrophage-mediated bacterial phagocytosis and intracellular killing of P. aeruginosa by targeting Rheb (Ras homolog enriched in brain). To the best of our knowledge, this is the first study to explore the role of miR-155 in bacterial keratitis, which may provide a promising target for clinical treatment of P. aeruginosa keratitis and other infectious diseases.