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

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Figueiredo Leite, Giuseppe Gianini ^[1] ; Ferreira, Bianca Lima ^[1] ; Tashima, Alexandre Keiji ^[2] ; Nishiduka, Erika Sayuri ^[2] ; Cunha-Neto, Edecio ^[3] ; Colo Brunialti, Milena Karina ^[1] ; Assuncao, Murillo ^[4] ; Pontes Azevedo, Luciano Cesar ^[5] ; Freitas, Flavio ^[6] ; van der Poll, Tom ^{[7, 8]} ; Scicluna, Brendon P. ^{[7, 9]} ; Salomao, Reinaldo ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Med, Div Infect Dis, Escola Paulista Med, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Biochem, Escola Paulista Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Coracao, Lab Imunol, Hosp Clin, Fac Med, Sao Paulo - Brazil

^[4] Hosp Israelite Albert Einstein, Intens Care Unit, Sao Paulo - Brazil

^[5] Hosp Sirio Libanes, Intens Care Unit, Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, Intens Care Unit, Escola Paulista Med, Hosp Sao Paulo, Sao Paulo - Brazil

^[7] Univ Amsterdam, Amsterdam Univ Med Ctr, Acad Med Ctr, Ctr Expt & Mol Med, Amsterdam - Netherlands

^[8] Univ Amsterdam, Amsterdam Univ Med Ctr, Acad Med Ctr, Div Infect Dis, Amsterdam - Netherlands

^[9] Univ Malta, Mater Dei Hosp, Fac Hlth Sci, Dept Appl Biomed Sci, Msida - Malta

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 12, SEP 10 2021.
• Citações Web of Science: 0

Resumo

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.</p> (AU)

• Processo FAPESP: 19/20532-3 - Análise proteômica quantitativa nas amostras de células mononucleares (PBMC) e polimorfonucleares (PMN) de pacientes com Sepse e voluntários sadios, com foco em proteínas relacionadas ao metabolismo energético e oxidativo, além da função mitocondrial
• Beneficiário: Giuseppe Gianini Figueiredo Leite
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/21052-0 - Sepse: mecanismos, alvos terapêuticos e epidemiologia
• Beneficiário: Reinaldo Salomão
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/13855-2 - Análise do metabolismo energético e oxidativo de células mononucleares de sangue periférico (PBMC) de pacientes sépticos
• Beneficiário: Bianca Rodrigues Lima Ferreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado