Molesworth-Kenyon Sara J, Yin Rong, Oakes John E, Lausch Robert N
Department of Microbiology and Immunology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
J Leukoc Biol. 2008 Feb;83(2):401-8. doi: 10.1189/jlb.0807571. Epub 2007 Nov 12.
IL-17 has been associated with selected inflammatory and autoimmune diseases. We characterized the expression of this proinflammatory cytokine following HSV-1 corneal infection and investigated whether IL-17R signaling modulated the host response to the viral pathogen at early time-points postinfection. IL-17 was elevated in the murine cornea 24 h after high-dose virus infection and subsequently persisted at low levels during the first week. Immunofluorescent studies showed that the IL-17R was expressed by cultured mouse corneal fibroblasts. Exposure of corneal cells to IL-17 led to production of IL-6 and MIP-2 in vitro and in vivo, indicating that the IL-17R was functional. Mice lacking IL-17R displayed significantly reduced neutrophil infiltration and corneal opacity. However, this effect was transient, as corneal pathology and neutrophil influx resembled that of wild-type (WT) hosts 4 days postinfection. HSV-1 growth and clearance in IL-17R(-/-) hosts were similar to that of the WT controls. Infection of IFN-gamma gene knockout mice was associated with elevated IL-17 levels and accelerated corneal opacity, suggesting that IFN-gamma negatively regulated IL-17 expression. Collectively, our results establish that IL-17 is rapidly produced in the cornea after HSV-1 infection and is regulated at least in part by IFN-gamma. The absence of IL-17 signaling results in a transient decrease in the expression of proinflammatory mediators, neutrophil migration, and corneal pathology, but control of virus growth in the cornea and trigeminal ganglia is not compromised. Thus, IL-17 actively influences early virus-induced corneal inflammation.
白细胞介素-17（IL-17）与某些炎症性和自身免疫性疾病有关。我们对单纯疱疹病毒1型（HSV-1）角膜感染后这种促炎细胞因子的表达进行了表征，并研究了IL-17R信号传导在感染后早期是否调节宿主对病毒病原体的反应。高剂量病毒感染后24小时，小鼠角膜中的IL-17升高，随后在第一周内持续处于低水平。免疫荧光研究表明，培养的小鼠角膜成纤维细胞表达IL-17R。角膜细胞暴露于IL-17会在体外和体内导致IL-6和MIP-2的产生，表明IL-17R具有功能。缺乏IL-17R的小鼠中性粒细胞浸润和角膜混浊明显减少。然而，这种作用是短暂的，因为感染后4天角膜病理和中性粒细胞流入与野生型（WT）宿主相似。HSV-1在IL-17R（-/-）宿主中的生长和清除与WT对照相似。干扰素-γ（IFN-γ）基因敲除小鼠的感染与IL-17水平升高和角膜混浊加速有关，表明IFN-γ负调节IL-17表达。总体而言，我们的结果表明，HSV-1感染后角膜中会迅速产生IL-17，并且至少部分受IFN-γ调节。IL-17信号的缺失导致促炎介质表达、中性粒细胞迁移和角膜病理的短暂减少，但角膜和三叉神经节中病毒生长的控制并未受到损害。因此，IL-17积极影响早期病毒诱导的角膜炎症。
