Molecular signature related to low density neutrophils in different types of infections

• Grant number: 22/13073-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2022
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Reinaldo Salomão
• Grantee: João Victor Souza de Lima
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 17/21052-0 - Sepsis: mechanisms, therapeutic targets and epidemiology, AP.TEM

Abstract

Low Density Neutrophils (LDNs) and Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are terms designating the same type of immune cells which on the one hand seem to be associated with reduced antigen presentation capacity and inhibition of T lymphocyte activation and proliferation, but on the other hand appear to have increased functions such as production of neutrophil extracellular traps (NETs) and generation of reactive oxygen species (ROS). To understand if there is a molecular signature associated with the presence of LDNs in Peripheral Blood Mononuclear Cells (PBMC) samples from patients with infection, compare them with findings in patients with sepsis and estimate what functions are performed by these cells, we manually selected from the Gene Expression Omnibus (GEO), European Genome-phenome Archive (EGA) and Proteomics Identification Database (PRIDE) databases the datasets that met the following criteria: (i) human PBMCs; (ii) infection; and (iii) presence of healthy controls. Exclusion criteria were i) PBMC collected from animals and ii) low number of samples (n<5) and healthy controls (n<3). A total of 14 sets were selected for individual analysis using R software (version 4.0.2) and the packages limma, tydiverse and dplyr. Differentially Expressed Genes (DEGs) meeting the criteria will be selected: P-value < 0.05 and Log2 Fold-Change <-1 and >1. With the lists of DEGs obtained, we will use the MetaVolcanoR package to combine them all into a single list.