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Evaluation of the effect of butyrate on the differentiation and migration of plasmacytoid dendritic cells during severe lung inflammation by the SARS-CoV-2 virus in an experimental model

Grant number: 22/03755-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2022
Effective date (End): August 31, 2024
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Daniela Carlos Sartori
Grantee:Jéssica Assis Pereira
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The SARS-CoV-2 virus, which causes COVID-19 (disease coronavirus 2019) was identified in December 2019 in Wuhan province in China, where the first cases were related to the Huanan seafood market in the city of Huanan. Wuhan. COVID-19 has diverse symptoms and can have varied clinical manifestations among patients, from asymptomatic patients to patients who develop severe symptoms. Thus, pharmacological or immunological interventions aimed at enhancing host defense and/or limiting excessive inflammation may be important to improve the prognosis of pulmonary infections by the virus. SARS-CoV-2 infection induces reduced dendritic cell activation, which causes a defective T cell response, and there are reports of decreased and loss of plasmacytoid dendritic cell (pDC) function in severe cases of COVID-19. . Studies have also revealed that the gut microbiota of COVID-19 patients showed a more pathobiont profile characterized by enrichment of opportunistic pathogens, along with a significant reduction in beneficial butyrate-producing bacteria, and these changes in the microbiota are also related to severe cases of the disease. infection. In addition to activating and regulating immune responses on mucosal surfaces, the intestinal microbiota plays an important role in the development and maturation of the immune system. Studies have shown a fundamental role of short-chain fatty acids (SCFA) in the hematopoiesis of immune system cells, suggesting that microbiota metabolites may play a role in COVID-19. Therefore, the objective of this work will be to evaluate the role of butyrate in the process of pDC hematopoiesis in the bone marrow, and its subsequent migration to the lung tissue during SARS-CoV-2 virus infection.

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