Cellular and Exosomal Regulations of Sepsis-Induced Metabolic Alterations

Abstract

Sepsis is a sustained systemic inflammatory condition involving multiple organ failures caused by dysregulated immune response to infections. Sepsis induces substantial changes in energy demands at the cellular level leading to metabolic reprogramming in immune cells and stromal cells. Although sepsis-associated organ dysfunction and mortality have been partly attributed to the initial acute hyperinflammation and immunosuppression precipitated by a dysfunction in innate and adaptive immune responses, the late mortality due to metabolic dysfunction and immune paralysis currently represent the major problem in clinics. It is becoming increasingly recognized that intertissue and/or intercellular metabolic crosstalk via endocrine factors modulates maintenance of homeostasis, and pathological events in sepsis and other inflammatory diseases. Exosomes have emerged as a novel means of intercellular communication in the regulation of cellular metabolism, owing to their capacity to transfer bioactive payloads such as proteins, lipids, and nucleic acids to their target cells. Recent evidence demonstrates transfer of intact metabolic intermediates from cancer-associated fibroblasts via exosomes to modify metabolic signaling in recipient cells and promote cancer progression. Here, we review the metabolic regulation of endothelial cells and immune cells in sepsis and highlight the role of exosomes as mediators of cellular metabolic signaling in sepsis.

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“…1 ). The cell membranes that are damaged under systemic hyperinflammatory conditions include those of the mitochondria with energy failure being commonplace in these diseased situations [ 79 ]. By inhibiting cyclooxygenase, melatonin attenuates the hyperinflammatory response that accompanies a SARS-CoV-2 infection [ 80 ].…”

Mechanisms underlying the therapeutic effects of 4-octyl itaconate in treating sepsis based on network pharmacology and molecular docking

“…It may also be related to complex disorders of immune metabolism, which is one of the reasons that hinder the development of effective drugs for sepsis ( Weis et al, 2017 ; Koutroulis et al, 2019 ). In addition, disease tolerance is becoming a hub strategy for treating sepsis, and its mechanisms involve aspects such as immune metabolism, immune fitness, inflammation, and genetics ( Appiah et al, 2021 ). Relevant studies have shown that the innate and adaptive immune systems play an essential role in disease tolerance defense ( McCarville and Ayres, 2018 ).…”

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