Scholarship 23/12861-2 - Inflamação, Inflamassomos - BV FAPESP
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The participation of the inflammasome in the response against SARS-CoV-2 and Influenza infections in an experimental murine model

Grant number: 23/12861-2
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: April 01, 2024
End date until: June 30, 2027
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Dario Simões Zamboni
Grantee:Felipe Teixeira Lopes
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:19/11342-6 - Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens, AP.TEM

Abstract

The immunological response in the nasal and oral mucosa is crucial to contain viral particles, where viral neuraminidase (NA) facilitates the penetration of the influenza virus through mucus into the respiratory epithelium. After infection with this virus, events such as the expression of the M2 ion channel, the perturbation of mitochondrial membrane potential and the accumulation of viral RNA in the cytosol lead to the activation of the inflammasome and the release of IL-1², resulting in the death of infected cells. . The immune system uses endosomal TLRs, such as TLR7, TLR3 and TLR8, to recognize viral RNA. In the upper respiratory tract, immunological defense is driven by IgA antibodies and mucosal mucus. In COVID-19, marked lung inflammation occurs, possibly due to the release of chemokines, accompanied by a reduction in dendritic cells, plasmacytoid dendritic cells, and NK cells in the lung and blood. NLRP3 inflammasome activation is observed in both influenza and SARS-CoV-2 infections, contributing to exacerbated inflammation and adverse clinical outcomes. However, unresolved questions remain regarding the relationship between inflammasome activation and lung inflammation during viral infections. In this project, our objective is to evaluate the role of the inflammasome in the response to SARS-CoV-2 and influenza infections in murine experimental models.

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