Study of T cell-mediated immunity in experimental COVID-19: involvement of purinergic signaling

• Grant number: 22/07800-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2022
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Maria Regina D'Império Lima
• Grantee: Marcos Vinícios Pinheiro Cione
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis, AP.TEM

Abstract

The SARS-CoV-2 pandemic has been one of the most devastating episodes of all humanity, killing more than 6.3 million people since the emergence of the disease. Although prophylactic measures have been adopted to contain the pandemic, such as mass vaccination, personal hygiene and social distancing, the lack of an effective treatment or prophylactic measure against the infection has been one of the biggest obstacles to the end of the pandemic. Currently, the humoral response is the basis of vaccine protection generated against the SARS-CoV-2 virus. Despite this, this response is not long-lasting and may be affected by the appearance of new variants and fail to protect against reinfections in the long term. On the other hand, we know that the T lymphocyte-mediated response is long-lasting and potent to prevent viral reinfections. The presence of memory resident T cells (MRTs) in the lungs during viral infections reveals the immune system's ability to generate a specific and lasting type of memory in non-lymphoid organs. Recent studies indicate that the generation and maintenance of TRM cells in the lungs is dependent on the activation of the purinergic receptor P2X7 by extracellular ATP (eATP), but this phenomenon has not yet been investigated in COVID-19. On the other hand, our research group showed that signaling through P2RX7 is essential for the accumulation of effector T lymphocytes in the lung parenchyma during influenza virus infection. Therefore, this project proposes to determine the immunization conditions to optimize the generation and maintenance of the response of specific T lymphocytes to SARS-CoV-2 in the lungs, as well as to establish an experimental model to evaluate the protection conferred by these cells without interference of B lymphocytes. The participation of the eATP-P2RX7 axis as an inducing signaling of migration and proliferation of SARS-CoV-2 specific T lymphocytes in the lung parenchyma, which favors the permanence of TRMs cells, will also be investigated in order to develop new preventive strategies against COVID-19.