The host in Sepsis: metabolism, biological processes and characterization of response profiles

• Grant number: 24/01786-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: April 01, 2025
• End date: March 31, 2030
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Reinaldo Salomão
• Grantee: Reinaldo Salomão
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Alexandre Keiji Tashima ; Ana Claudia Trocoli Torrecilhas ; Flavia Ribeiro Machado ; Flávio Geraldo Rezende de Freitas ; Giuseppe Gianini Figueiredo Leite ; Letícia Sandre Vendrame Saes ; Lucio Roberto Requiao Moura

Abstract

Sepsis is defined as severe, potentially fatal organ dysfunction caused by an inadequate or dysregulated host response to infection. It is extremely relevant in public health due to its high morbidity and mortality, being recognized as a global health priority by the World Health Organization, with around 48.9 million cases and 11 million related deaths estimated in 2017.The host response is a central event in pathogenesis and intrinsically associated with the concept of sepsis, with energy metabolism being fundamental in its regulation. With this focus, we addressed metabolism and dysregulation of the immune response in our current thematic project (Process 2017-21052), with an emphasis on peripheral blood mononuclear cells (PBMC). Expanding the evaluation of peripheral blood cells, in the current project, we will emphasize the study of neutrophils and extracellular vesicles.The use of "omics" tools, such as transcriptomics, proteomics and lipidomics, has led to the characterization of patient profiles (endotypes) with distinct responses to infection, associated with different sepsis outcomes. These profiles are seen as a pathway to unveil the heterogeneity of sepsis and drive appropriate interventions for each profile, towards personalized medicine. We obtained interesting results combining transcriptomics and proteomics in patients with sepsis and COVID-19, including the relevance of a signature related to LDN. In the current project we will explore the presence and relationship of proteins related to this signature with inflammatory and vascular mediators, associating them with organic dysfunction and clinical outcome, eventually characterizing a "signature" of response in sepsis.Our previous studies evaluating the host response in sepsis were based on patient populations admitted to Intensive Care Units and included individuals with different comorbidities. Investigating patients with COVID-19, we had the opportunity to evaluate the response in a specific population, that of kidney transplant recipients (TXR), whose underlying disease and therapeutic interventions imply a complex interaction with the infectious agent. This population has been the target of interest in the study of sepsis and COVID-19 and, in the current project, we will constitute a TXR cohort with sepsis. (AU)