IL-17 receptor signaling influences virus-induced corneal inflammation
IL-17 receptor signaling influences virus-induced corneal inflammation
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DOI：
10.1189/jlb.0807571
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发表时间：
2008-02-01
影响因子：
5.5
通讯作者：
Lausch, Robert N.
中科院分区：
文献类型：
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作者：
Molesworth-Kenyon, Sara J.;Yin, Rong;Lausch, Robert N.
IL-17与某些炎症和自身免疫性疾病有关。我们描述了这种促炎细胞因子在HSV-1角膜感染后的表达，并研究了IL-17R信号是否在感染后早期时间点调节宿主对病毒病原体的反应。IL-17在大剂量病毒感染后24小时在小鼠角膜中升高，随后在第一周内维持在低水平。免疫荧光研究表明，IL-17R在培养的小鼠角膜成纤维细胞中表达。将角膜细胞暴露于IL-17中，可导致体内和体外产生IL-6和MIP-2，表明IL-17R具有功能。缺乏IL-17R的小鼠表现出明显减少的中性粒细胞浸润和角膜混浊。然而，这种影响是短暂的，因为角膜病理和中性粒细胞内流与野生型（WT）宿主感染后4天相似。在IL-17R（-/-）宿主中，HSV-1的生长和清除率与WT对照组相似。ifn - γ基因敲除小鼠感染与IL-17水平升高和角膜混浊加速相关，提示ifn - γ负调控IL-17表达。总的来说，我们的结果表明，在HSV-1感染后，IL-17在角膜中迅速产生，并且至少部分受到ifn - γ的调节。IL-17信号的缺失导致促炎介质的表达、中性粒细胞迁移和角膜病理的短暂减少，但对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。
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.