| Full text | |
| Author(s): |
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
Total Authors: 8
|
| Document type: | Journal article |
| Source: | FRONTIERS IN IMMUNOLOGY; v. 13, p. 10-pg., 2022-11-18. |
| Abstract | |
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) | |
| FAPESP's process: | 16/13855-2 - Evaluation of energy and oxidative metabolism in peripheral blood mononuclear cells (PBMC) from septic patients |
| Grantee: | Bianca Rodrigues Lima Ferreira |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 20/05077-5 - Changes in energy metabolism of endotoxin tolerant peripheral blood mononuclear cells |
| Grantee: | Mônica Bragança Sousa |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 17/21052-0 - Sepsis: mechanisms, therapeutic targets and epidemiology |
| Grantee: | Reinaldo Salomão |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 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 |
| Grantee: | Giuseppe Gianini Figueiredo Leite |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |