Immune mechanisms of post-infectious uveitis

感染后葡萄膜炎的免疫机制

• 批准号: 10670933
• 负责人: Kathryn Pepple
• 金额: $ 44.13万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10670933
• 关键词: Adenoviruses; Affect; Antigens; Autoimmune Process; Autoimmune Responses; B-Lymphocytes; Biodistribution; CD4 Positive T Lymphocytes; Chronic; Data; Development; Disease; Eye; Eye Infections; Gene Transduction Agent; Immune; Immune response; Immunization; Immunology procedure; Immunosuppression; Infection; Inflammation; Knowledge; Lymphocyte; Mediating; Mycobacterium Infections; Nature; Outcome; Pathogenesis; Patients; Persons; Population; Prevention strategy; Proteins; Resolution; Role; Satellite Viruses; Signal Transduction; Specificity; Systemic infection; T cell response; T-Lymphocyte; Testing; Time; Uveitis; Viral Genes; Visual; adaptive immune response; adeno-associated viral vector; antimicrobial; cytokine; effective therapy; effector T cell; improved; microorganism antigen; mouse model; mycobacterial; pathogen; pathogen exposure; treatment strategy

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.

摘要 葡萄膜炎，或眼部炎症，是一种致盲疾病，影响了大约30万人， 美国，以及全世界数百万人。慢性形式的葡萄膜炎与不良的视力结果相关， 需要长期的免疫抑制治疗感染后葡萄膜炎是一种破坏性的慢性 在眼部或全身感染后发生的葡萄膜炎，治疗具有挑战性。 严重缺乏对感染后疾病的基本机制的了解， 色素层炎。这限制了有效治疗策略和新治疗选择的发展。 目前，对于感染后葡萄膜炎是否是由死亡的 微生物抗原保留在眼睛中，或由无意中触发的自身免疫反应产生 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 称为致敏分枝杆菌葡萄膜炎（PMU）。我们的初步数据显示， 免疫系统对于慢性葡萄膜炎是必需的，并支持疾病的自身免疫机制。 在目前的建议中，我们将扩展我们的初步研究结果，以建立一个更详细的了解， 机制负责感染后葡萄膜炎和测试的假设，慢性感染后 葡萄膜炎由从头T细胞介导的对眼抗原的适应性免疫应答引起。