Importance of the Aim2 Inflammasome in the Response to Betacoronavirus Infection

• Grant number: 24/07282-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2024
• End date: December 31, 2027
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Dario Simões Zamboni
• Grantee: Keise Adrielle Santos Pereira
• 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

Coronavirus disease 2019 (COVID-19) is characterized by an exacerbated inflammatory response caused by the SARS-CoV-2 virus. The disease has affected millions of people around the world, causing a global public health crisis, with around 6.9 million deaths to date. Despite vaccination, outbreaks and isolated cases of COVID-19 continue to occur. In addition, only 17.4% of people in low-income countries have received the first dose of the vaccine. The clinical spectrum of COVID-19 ranges from mild to moderate, severe and critical illness. The latter two are characterized by immune dysregulation and a cytokine storm, with a sudden increase in pro-inflammatory cytokines and other inflammatory markers. The innate immune system is essential for the initial recognition of pathogens. In addition to Toll-like receptors, RIG-I and CLRs, NLRs also play an important role in the recognition process of pathogens such as SARS-CoV-2. NLRs are multiprotein cytosolic complexes called inflammasomes. Deregulated activation of the inflammasome and the consequent production of inflammatory cytokines has been associated with the severity of COVID-19. Our group demonstrated that the NLRP3 inflammasome is active in patients with moderate and severe COVID-19 through the formation of NLRP3 and ASC "puncta" in lung tissues of patients who died from COVID-19. Another study demonstrated the presence of the NLRP3 and AIM2 inflammasome in monocytes from COVID-19 patients. In preliminary investigations carried out by our group (unpublished data), we verified the existence of AIM2 puncta in tracheal hair cells of patients who died from COVID-19, suggesting an important role of the AIM2 inflammasome in epithelial cells during COVID-19. Therefore, in order to better understand the pathogenesis of the disease and discover new therapeutic targets, it becomes relevant to investigate other inflammasomes involved in the poor prognosis of the disease, especially the AIM2 inflammasome and the participation of lung epithelial cells in this response during the development of moderate and severe COVID-19.