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.
Highlights
Sepsis results from a dyshomeostatic response to infection, which may lead to hyper or hypoimmune states
We report the alterations in the proteomic phenotype of blood monocytes from patients with septic shock
In the acute stage of septic shock, the observed protein expression levels were indicative of a shift from oxidative phosphorylation to glycolysis, compatible with the Warburg effect
Summary
Sepsis results from a dyshomeostatic response to infection, which may lead to hyper or hypoimmune states. In shock states the main cause of organ failure is a reduction in oxygen delivery, in septic shock, oxygen consumption may remain impaired despite restored tissue perfusion This observation led to the hypothesis that sepsis-induced primary bioenergetic alterations may be relevant disease m echanisms[5,6]. Monocytes act as direct effectors of innate immunity, exhibiting phagocytic microbicidal activity, producing inflammatory mediators, presenting antigens, and influencing the adaptive immune response[7,8]. These cells are potential critical elements for the genesis and resolution of sepsis. It is important that disease-specific phenotypes be characterized directly from clinical samples
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