Evaluation of differential activation of inflammasomes in murine and human glial cells and neurons in response to viral infections

• Grant number: 20/13493-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2022
• Effective date (End): September 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Karina Ramalho Bortoluci
• Grantee: Ingrid Sancho de Farias
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Several viruses have the ability to invade the Central Nervous System (CNS), which can infect resident cells and cause severe neuroinflammation by activating the innate immune system. It is known that these highly inflammatory processes are influenced by the activation of inflammasomes, which are multiprotein platforms present in the cytosol of different cell types, capable of activating the caspase-1 protease, leading to the secretion of IL-1²/IL-18 and cell death by pyroptosis. It has been shown that the Zika Virus (ZIKV) is capable of modulating the activation of inflammasomes in different cell types, generating different responses. However, ZIKV mainly infects cells of the CNS and the role of inflammasome activation in these cells is not well established. Like other well-known human neuroinvasive viruses, respiratory viruses can also damage the CNS as a result of poorly targeted immune responses from the host, and SARS-CoV2 infection is increasingly being linked to neurological damage. It is known that infection with the new coronavirus can stimulate a storm of inflammatory cytokines promoting Acute Respiratory Difficulty Syndrome (ARDS), fibrosis, hematological and neurological disorders, among others, which can lead to organ failure and death. Recently, the activation of inflammasomes in monocytes of patients with COVID-19 has been demonstrated and the relationship of this activation with the severity of the disease. However, the role of these platforms in the SNC is unknown. Thus, considering that the activity of inflammasomes is critical for the host's response to pathogens, and may also result in exacerbation of neuropathologies, the objective of this project is to elucidate the mechanisms by which inflammasomes are modulated in response to viral infections in CNS cells. murine and human and the consequences of its activation for the control of infection and neuroinflammation. (AU)