Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function

Autor(es)

Ferreira, Bianca Lima ; Sousa, Monica Braganca ; Leite, Giuseppe Gianini Figueiredo ; Brunialti, Milena Karina Colo ; Nishiduka, Erika Sayuri ; Tashima, Alexandre Keiji ; van der Poll, Tom ; Salomao, Reinaldo

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 13, p. 10-pg., 2022-11-18.

Resumo

Metabolic adaptations shape immune cell function. In the acute response, a metabolic switch towards glycolysis is necessary for mounting a proinflammatory response. During the clinical course of sepsis, both suppression and activation of immune responses take place simultaneously. Leukocytes from septic patients present inhibition of cytokine production while other functions such as phagocytosis and production of reactive oxygen species (ROS) are preserved, similarly to the in vitro endotoxin tolerance model, where a first stimulation with lipopolysaccharide (LPS) affects the response to a second stimulus. Here, we sought to investigate how cellular metabolism is related to the modulation of immune responses in sepsis and endotoxin tolerance. Proteomic analysis in peripheral blood mononuclear cells (PBMCs) from septic patients obtained at intensive care unit admission showed an upregulation of proteins related to glycolysis, the pentose phosphate pathway (PPP), production of ROS and nitric oxide, and downregulation of proteins in the tricarboxylic acid cycle and oxidative phosphorylation compared to healthy volunteers. Using the endotoxin-tolerance model in PBMCs from healthy subjects, we observed increased lactate production in control cells upon LPS stimulation, while endotoxin-tolerant cells presented inhibited tumor necrosis factor-alpha and lactate production along with preserved phagocytic capacity. Inhibition of glycolysis and PPP led to impairment of phagocytosis and cytokine production both in control and in endotoxin-tolerant cells. These data indicate that glucose metabolism supports leukocyte functions even in a condition of endotoxin tolerance. (AU)

• 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
• Processo FAPESP: 20/05077-5 - Alterações do metabolismo energético em células mononucleares de sangue periférico tolerantes à endotoxina
• Beneficiário: Mônica Bragança Sousa
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/21052-0 - Sepse: mecanismos, alvos terapêuticos e epidemiologia
• Beneficiário: Reinaldo Salomão
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• 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