Microbiota association with immune system activation in the autoimmune uveitis development

• Grant number: 22/01362-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2023
• Status: Discontinued
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Luiz Vicente Rizzo
• Grantee: Danielle Dias Munhoz
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil
• Associated scholarship(s): 24/06803-2 - Gut microbiome analvsis in autoimmune uveitis: Investigating immunological triggers, BE.EP.PD

Abstract

Autoimmune uveitis is a T cell driven intraocular inflammation that affects the neuroretin causing severe eye damage and blindness. The eye has an immunological privilege due to the anti-inflammatory molecules present in the milieu that surround its components and by the Blood-Retinal Barrier (BRB), which keeps the exclusive ocular antigens and effector T cell targets in uveitis restricted to the organ and separated from the immune system. Due to this immunological restriction, uveitis represents a paradox, in which T cells specific for retinal antigens must be previously activated to be able to cross the BRB and trigger the inflammatory process, raising the fundamental question of how and where these cells are activated acquiring the ability to induce disease. Data suggest that bacterial peptides from the microbiota may mimic the retinal antigen, leading to activation of the immune system through the specific T cell receptor and, thus, triggering the disease. Bioinformatics analyzes identified bacterial peptides with significant homology to the Interphotoreceptor Retinoid Binding Protein (IRBP), one of the main target antigens of uveitis, which may indicate an important relationship between components of the microbiota with the development of the disease. In addition to supposedly serving as a trigger, the microbiota may also act as an adjuvant providing signals that amplify and direct the immune response to autopathogenicity. Thus, this project aims to investigate the association between microbiota components and the activation of the immune system with further development of autoimmune uveitis. The autoimmune uveitis animal model will be colonized with bacterial knockouts in the targets that supposedly mimic IRBP in order to identify the microorganisms and microbial antigens that may trigger the disease, which would have extensive implications in the improvement of disease development characterization, in addition to be able to assist in its diagnosis and therapy.