Immune mechanisms of post-infectious uveitis

摘要 葡萄膜炎，或称眼部炎症，是一种致盲疾病，影响着世界上约30万人 美国，以及全世界数百万人。慢性葡萄膜炎与视力不良和 需要长期的免疫抑制疗法。感染后葡萄膜炎是一种毁灭性的慢性葡萄膜炎 葡萄膜炎是在眼睛或全身感染后发展起来的，很难治疗。有一个 对感染后致病的基本机制缺乏了解 葡萄膜炎。这限制了有效治疗策略和新治疗选择的发展。 目前，关于感染后葡萄膜炎是否由死者的存在引起的争论还在继续。 微生物抗原保留在眼睛内，或由无意中触发的自身免疫反应产生 被感染。为了回答这个问题，我们建立了一个慢性感染后葡萄膜炎的小鼠模型。 称为初级细菌性葡萄膜炎(PMU)。我们的初步数据显示，适应性但不是先天的 免疫系统是慢性葡萄膜炎所必需的，并支持疾病的自身免疫机制。 在目前的提案中，我们将扩展我们的初步调查结果，以建立对 感染后葡萄膜炎的机制和检验慢性感染后葡萄膜炎的假设 葡萄膜炎是由新生T细胞介导的对眼部抗原的适应性免疫反应引起的。

Abstract Uveitis, or ocular inflammation, is a blinding condition that affects around 300,000 people in the US, and millions world-wide. Chronic forms of uveitis are associated with poor visual outcomes and require long-term immune suppression therapy. Post-infectious uveitis is a devastating form of chronic uveitis that develops after an ocular or a systemic infection and is challenging to treat. There is a significant lack of understanding about the fundamental mechanisms responsible for post-infectious uveitis. This has limited the development of effective treatment strategies and new treatment options. Currently, there is debate whether post-infectious uveitis is caused by the presence of killed microbial antigens retained in the eye, or generated by an inadvertent autoimmune response triggered by infection. To answer this question, we developed a mouse model of chronic post-infectious uveitis termed primed mycobacterial uveitis (PMU). Our preliminary data show that the adaptive but not innate immune system is necessary for chronic uveitis, and supports an autoimmune mechanism of disease. In the current proposal we will extend our initial findings to build a more detailed understanding of the mechanisms responsible for post-infectious uveitis and test the hypothesis that chronic post-infectious uveitis results from a de novo T-cell mediated adaptive immune response to ocular antigens.