1. Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock
- Author
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Giselle Villa Flor Brunoro, Helder I. Nakaya, Monique R.O. Trugilho, Patrícia T. Bozza, Richard H. Valente, Fernando A. Bozza, Pedro Mendes de Azambuja Rodrigues, and Mariana Araujo-Pereira
- Subjects
0301 basic medicine ,Male ,Proteomics ,Immunopathogenesis ,Science ,Immunology ,Pathogenesis ,Monocytes ,Article ,Proinflammatory cytokine ,Sepsis ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Downregulation and upregulation ,Immunopathology ,medicine ,Humans ,Prospective Studies ,Aged ,Aged, 80 and over ,Inflammation ,Multidisciplinary ,Septic shock ,business.industry ,Monocyte ,Histocompatibility Antigens Class II ,Immunity ,PROTEÔMICA ,Middle Aged ,medicine.disease ,Shock, Septic ,030104 developmental biology ,medicine.anatomical_structure ,Case-Control Studies ,Cytokines ,Medicine ,Female ,Immunocompetence ,business ,Energy Metabolism ,Infection ,030217 neurology & neurosurgery - 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.
- Published
- 2021