Combined Transcriptome and Proteome Leukocyte’s Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis
Open Access
- 10 September 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 12, 744799
- https://doi.org/10.3389/fimmu.2021.744799
Abstract
Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in “omics” technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co‐differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down‐regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up‐regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host‐defense system.Funding Information
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Fundação de Amparo à Pesquisa do Estado de São Paulo
This publication has 64 references indexed in Scilit:
- C-type lectin receptor Clec4d plays a protective role in resolution of Gram-negative pneumoniaJournal of Leukocyte Biology, 2013
- A genomic storm in critically injured humansThe Journal of Experimental Medicine, 2011
- The Role of Natural Killer Cells in SepsisJournal of Biomedicine and Biotechnology, 2011
- Correlation of mRNA and protein in complex biological samplesFEBS Letters, 2009
- Absolute Quantification of Proteins by LCMSEMolecular & Cellular Proteomics, 2006
- A network-based analysis of systemic inflammation in humansNature, 2005
- Analysis of mRNA expression and protein abundance data: an approach for the comparison of the enrichment of features in the cellular population of proteins and transcriptsBioinformatics, 2002
- Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in SepsisSocial psychiatry. Sozialpsychiatrie. Psychiatrie sociale, 1992
- A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye BindingAnalytical Biochemistry, 1976
- Central Dogma of Molecular BiologyNature, 1970