Immune mechanisms of post-infectious uveitis

感染后葡萄膜炎的免疫机制

• 批准号: 10452583
• 负责人: Kathryn Pepple
• 金额: $ 42.8万
• 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/10452583
• 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