Impact of inflammasomes activation in central nervous system in response to ZikV e SARS-Cov2 infections

• Grant number: 21/03371-6
• Support Opportunities: Regular Research Grants
• Duration: October 01, 2021 - September 30, 2023
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Karina Ramalho Bortoluci
• Grantee: Karina Ramalho Bortoluci
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Juliana Terzi Maricato ; Marimélia Aparecida Porcionatto

Abstract

Several viruses have the ability to invade the Central Nervous System (CNS), infecting resident cells and causing severe neuroinflammation by activating the innate immune system. Exacerbated inflammatory responses 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) modulates the activation of inflammasomes in different cell types. However, ZIKV mainly infects the CNS cells, and the role of inflammasome activation in these cells is not well established. Respiratory viruses can also damage the CNS similar as other well-known human neuroinvasive viruses. In this sense, SARS-Cov2 infection is increasingly being linked to neurological damage. It is known that infection with the new coronavirus stimulates a storm of inflammatory cytokines promoting Acute Respiratory Difficulty Syndrome (ARDS), fibrosis, hematological and neurological disorders, among others, which can result in organ failure and death. Recently, it was described the correlation between the activation of inflammasomes and the severity of COVID-19. However, the role of these platforms in the SNC is still unknown. Thus, considering the crucial role of inflammasomes for the host's response to pathogens and the potential of these platforms to exacerbating neuropathologies, the objective of this project is to elucidate the mechanisms by which inflammasomes are modulated in response to viral infections in murine and human CNS cells and its consequences for the control of infection and neuroinflammation. (AU)