Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock
Abstract Sepsis results from a dyshomeostatic response to infection, which may lead to hyper or hypoimmune states. Monocytes are central regulators of the inflammatory response, but our understanding of their role in the genesis and resolution of sepsis is still limited. Here, we report a comprehens...
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2021-07-01
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doaj-869df548087c49c1885abac0b2e215812021-08-01T11:22:18ZengNature Publishing GroupScientific Reports2045-23222021-07-0111111010.1038/s41598-021-94474-0Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shockPedro Mendes de Azambuja Rodrigues0Richard Hemmi Valente1Giselle Villa Flor Brunoro2Helder Takashi Imoto Nakaya3Mariana Araújo-Pereira4Patricia Torres Bozza5Fernando Augusto Bozza6Monique Ramos de Oliveira Trugilho7National Institute of Infectious Diseases Evandro ChagasLaboratory of Toxinology, Oswaldo Cruz InstituteLaboratory of Toxinology, Oswaldo Cruz InstituteSchool of Pharmaceutical Sciences, University of São PauloSchool of Pharmaceutical Sciences, University of São PauloLaboratory of Immunopharmacology, Oswaldo Cruz InstituteNational Institute of Infectious Diseases Evandro ChagasLaboratory of Toxinology, Oswaldo Cruz InstituteAbstract Sepsis results from a dyshomeostatic response to infection, which may lead to hyper or hypoimmune states. Monocytes are central regulators of the inflammatory response, but our understanding of their role in the genesis and resolution of sepsis is still limited. Here, we report a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via proteomic profiling. The acute stage of septic shock was associated with an impaired inflammatory phenotype, indicated by the down-regulation of MHC class II molecules and proinflammatory cytokine pathways. Simultaneously, there was an up-regulation of glycolysis enzymes and a decrease in proteins related to the citric acid cycle and oxidative phosphorylation. On the other hand, the restoration of immunocompetence was the hallmark of recovering patients, in which an upregulation of interferon signaling pathways was a notable feature. Our results provide insights into the immunopathology of sepsis and propose that, pending future studies, immunometabolism pathway components could serve as therapeutic targets in septic patients.https://doi.org/10.1038/s41598-021-94474-0 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pedro Mendes de Azambuja Rodrigues Richard Hemmi Valente Giselle Villa Flor Brunoro Helder Takashi Imoto Nakaya Mariana Araújo-Pereira Patricia Torres Bozza Fernando Augusto Bozza Monique Ramos de Oliveira Trugilho |
spellingShingle |
Pedro Mendes de Azambuja Rodrigues Richard Hemmi Valente Giselle Villa Flor Brunoro Helder Takashi Imoto Nakaya Mariana Araújo-Pereira Patricia Torres Bozza Fernando Augusto Bozza Monique Ramos de Oliveira Trugilho Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock Scientific Reports |
author_facet |
Pedro Mendes de Azambuja Rodrigues Richard Hemmi Valente Giselle Villa Flor Brunoro Helder Takashi Imoto Nakaya Mariana Araújo-Pereira Patricia Torres Bozza Fernando Augusto Bozza Monique Ramos de Oliveira Trugilho |
author_sort |
Pedro Mendes de Azambuja Rodrigues |
title |
Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock |
title_short |
Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock |
title_full |
Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock |
title_fullStr |
Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock |
title_full_unstemmed |
Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock |
title_sort |
proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-07-01 |
description |
Abstract Sepsis results from a dyshomeostatic response to infection, which may lead to hyper or hypoimmune states. Monocytes are central regulators of the inflammatory response, but our understanding of their role in the genesis and resolution of sepsis is still limited. Here, we report a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via proteomic profiling. The acute stage of septic shock was associated with an impaired inflammatory phenotype, indicated by the down-regulation of MHC class II molecules and proinflammatory cytokine pathways. Simultaneously, there was an up-regulation of glycolysis enzymes and a decrease in proteins related to the citric acid cycle and oxidative phosphorylation. On the other hand, the restoration of immunocompetence was the hallmark of recovering patients, in which an upregulation of interferon signaling pathways was a notable feature. Our results provide insights into the immunopathology of sepsis and propose that, pending future studies, immunometabolism pathway components could serve as therapeutic targets in septic patients. |
url |
https://doi.org/10.1038/s41598-021-94474-0 |
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