The critical role of IFN-γ in experimental coronavirus retinopathy
The critical role of IFN-γ in experimental coronavirus retinopathy
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DOI：
10.1167/iovs.02-1106
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发表时间：
2003-08-01
影响因子：
4.4
通讯作者：
Detrick, B
中科院分区：
文献类型：
--
作者：
Hooks, JJ;Wang, Y;Detrick, B
目的。实验性冠状病毒视网膜病变(ECOR)是一种进行性视网膜疾病的动物模型，在遗传易感的BALB/c小鼠中，首先表现为急性视网膜炎症，然后是慢性免疫相关性视网膜变性。在抗视网膜退行性变的CD-1小鼠中，只有急性感染。本研究通过对ECOR过程中干扰素-γ的产生进行研究，并评价其在清除视网膜感染性病毒中的作用。免疫细胞化学染色检测小鼠眼内细胞浸润和主要组织相容性复合体(MHC)的表达。结果：BALB/c小鼠感染病毒后，全身干扰素-γ的发生率和水平增加。此外，在疾病的急性期，在感染动物的视网膜中检测到干扰素-γmRNA，但在正常或模拟注射的动物中未检测到。干扰素-γ在T细胞浸润时被检测到，早期的研究表明，这与颗粒酶B基因的表达和感染性病毒从视网膜上的清除有关。视网膜干扰素-γ基因的表达也与视网膜内MHC-I和II类分子的表达上调有关。当这种感染发生在干扰素-γGKO小鼠身上时，病毒不受控制，感染导致死亡。结论：这些研究表明，由细胞渗入视网膜产生的干扰素-γ是免疫机制的重要组成部分，负责将感染性病毒从视网膜上清除。
PURPOSE. Experimental coronavirus retinopathy (ECOR) is an animal model of progressive retinal disease that is first manifest as an acute retinal inflammation followed by chronic, immune-associated retinal degeneration in genetically susceptible, BALB/c mice. In retinal degeneration-resistant CD-1 mice, only the acute infection is seen. In the present study, interferon (IFN)-gamma production during ECOR was studied and its role evaluated in the clearance of infectious virus from the retina.METHODS. BALB/c, CD-1, and IFN-gamma- deficient (IFN-gamma gko) mice were inoculated with the JHM strain of murine coronavirus by the intravitreal route. Mouse eyes were evaluated for infiltrating cells and major histocompatibility complex (MHC) expression by immunocytochemical staining. Isolated retinas were analyzed for IFN-gamma mRNA by RT-PCR, and sera were evaluated for IFN-gamma protein by ELISA assays.RESULTS. Virus infection in BALB/c mice was associated with an increase in the incidence and levels of systemic IFN-gamma. Moreover, IFN-gamma mRNA was detected within the retinas of infected animals during the acute phase of the disease but was not detected in normal or mock-injected animals. IFN-gamma mRNA was detected at the time of T-cell infiltration, and earlier studies have shown that this is temporally related to granzyme B gene expression and the clearance of infectious virus from the retina. Retinal IFN-gamma mRNA was also associated with the upregulation of MHC class I and II molecules within the retina. When this infection occurred in IFN-gamma gko mice, the virus was unchecked, and the infection led to death.CONCLUSIONS. These studies indicate that generation of IFN-gamma by cells infiltrating the retina is an essential part of an immune mechanism responsible for noncytolytic clearance of infectious virus from the retina.