Characterization and immunomodulatory potential of extracellular vesicles from macrophages stimulated with SARS-CoV-2 particles

• Grant number: 22/07287-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2022
• Effective date (End): August 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Carlos Arterio Sorgi
• Grantee: Jonatan Constança Silva de Carvalho
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

SARS-CoV-2 infection has become a worldwide public health concern, severely affecting our society and economy, due to the disease's long incubation time and high prevalence. Thus, efforts were made to develop vaccines and antiviral treatments. The entry of SARS-CoV-2 into cells depends on binding to its ACE-2 receptor, triggering inflammatory cascades that are linked to the pathophysiology of COVID-19. In this way, effector cells of the immune system, such as macrophages and lymphocytes, release a large amount of pro-inflammatory cytokines and chemokines, leading to various clinical manifestations, such as high fever. In this context, a number of anti-inflammatory drugs were tested to inhibit the "cytokine storm" and multi-organ failure caused by hyperinflammation in critically ill patients, but the effect was not significant. In recent years, research has reported that extracellular vesicles (EVs) could be therapeutic targets in the treatment of inflammation and lung injury in respiratory viral infections. Thus, the interaction between EVs and the virus provides a new perspective on the treatment of COVID-19. EVs released from various cell types contribute to intercellular communication by delivering biomolecules such as nucleic acids, proteins, and lipids to recipient cells. In vitro studies have shown that EVs play key roles in infectious diseases. However, little is known about the characterization and function of EVs formed by macrophages infected with SARS-CoV-2 and thus, further scrutiny is warranted. In this project, we aim to produce in vitro EVs from human THP-1 macrophages under different polarization/activation conditions, as well as stimulated with SARS-CoV-2 viral particles. After obtaining and physical characterization of these EVs, we intend to understand the immunomodulatory role of EVs in epithelial cells involved in COVID-19 infection. Thus, increasing our knowledge of the dynamics of this virus and helping to develop more effective treatment modalities.