Evaluation of the steps of inflammasome activation in astrocytes in response to Zika virus

• Grant number: 23/04454-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2023
• Effective date (End): December 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Karina Ramalho Bortoluci
• Grantee: Victoria Weise Leite de Lucena
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Inflammasomes are cytosolic multiprotein complexes activated in response to infection or cell damage. The activation of these platforms leads to recruitment and self-cleavage of the effector protease caspase-1 and consequent release of IL-1B and IL-18, and induction of a specific form of cell death, pyroptosis. These complexes are found in various immune cells such as macrophages, neutrophils, and dendritic cells, but their presence has been characterized in other cells, such as epithelial cells and the Central Nervous System (CNS). In the CNS, the inflammasomes participate in infection control, but are also related to pathologies such as neurodegenerative diseases and neuropsychiatric disorders. Most studies of inflammasomes in the CNS are limited to mycroglia, since these cells compose the main immune axis of this compartment. Astrocytes are found in large numbers in the CNS and have essential functions for the functioning of neural circuits. Although the expression of inflammasomes and their components has been documented in astrocytes, the steps and mechanisms that lead to their activation, especially in the context of infection, are not clearly known. Thus, this project aims to understand the steps involved in the activation of inflammasomes in astrocytes facing Zika virus (ZIKV) infection, by analyzing the expression, assembly and functionality of inflammasomes. Thus, the results of this project will aid in understanding the role of inflammasomes in controlling ZIKV infection, as well as expanding the current knowledge of inflammasomes in astrocytes.