The role of MS1 monocytes in the host response during sepsis and pneumonia

• Grant number: 22/06085-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2023
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Reinaldo Salomão
• Grantee: Giuseppe Gianini Figueiredo Leite
• Supervisor: Tom van der Poll
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Amsterdam (UvA), Netherlands
• Associated to the scholarship: 19/20532-3 - Quantitative proteomic analysis in mononuclear (PBMC) and polymorphonuclear (PMN) cell samples from patients with Sepsis and healthy volunteers, focusing on proteins related to energy and oxidative metabolism, as well as mitochondrial function, BP.PD

Abstract

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The host response during sepsis shows signs of concurrent hyperinflammation and immunosuppression. A recent study identified a CD14+ monocyte phenotype in the blood of sepsis patients named MS1, characterized by high expression of RETN, ALOX5AP, and IL1R2, and the abundance of MS1 cells was associated with sepsis-induced immunosuppression. In this project we will seek to obtain more insight into the abundance and role of MS1 cells in critically ill patients with or without sepsis, and in patients hospitalized for community-acquired pneumonia. We will study the abundance of MS1 cells in blood of these patient groups using blood leukocyte genome-wide RNA profiles. We will assess the association of MS1 cells with the occurrence of secondary infections (a clinical outcome considered to be caused by immunosuppression) across two cohorts of critically ill patients, as well as the association between MS1 cells and concurrent disturbance of proinflammatory mechanisms implicated in sepsis pathogenesis (measured by a large set of host response biomarkers in plasma). In a third cohort, we will analyze the association of the MS1 signature in monocytes from patients with community-acquired pneumonia with the capacity of these cells to produce proinflammatory cytokines upon ex vivo stimulation. This project will provide in-depth insight into the frequency, function, and clinical relevance of a newly discovered cell type (MS1). (AU)