Metabolic reprogramming tailors T cell immunity in sepsis

TL;DR

This review explores how changes in T cell metabolism during sepsis weaken immunity and suggests new treatment strategies targeting these metabolic changes.

Contribution

The paper systematically reviews T-cell metabolic reprogramming in sepsis and proposes novel therapeutic strategies targeting metabolic pathways.

Findings

Sepsis causes T-cell metabolic reprogramming involving glycolysis, mitochondrial dysfunction, and amino acid metabolism.

Metabolic changes mediated by HIF-1α, mTOR, and AMPK contribute to T-cell exhaustion and immunosuppression.

Therapies like IL-7 and IDO1 inhibitors may restore T-cell function in sepsis.

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, characterized by persistently high morbidity and mortality. Current treatment strategies have limitations, particularly the persistence of an immunosuppressed state. Recent studies have revealed that sepsis not only causes immune system dysregulation but also leads to metabolic disturbances, specifically metabolic reprogramming in T cells—a field still in its early stages. This review systematically explores the mechanisms of T-cell metabolic reprogramming in sepsis, including enhanced glycolysis, mitochondrial dysfunction, and dysregulated amino acid metabolism. It further analyzes how these alterations, mediated by signaling pathways such as HIF-1α, mTOR, and AMPK, as well as key metabolic enzymes, exacerbate T-cell exhaustion and immunosuppression. The article elaborates on the role of metabolic reprogramming in T-cell dysfunction and susceptibility to secondary infections, and summarizes potential therapeutic strategies targeting metabolic pathways—such as IL-7 therapy and IDO1 inhibitors—for restoring T-cell function, offering new directions for sepsis immunotherapy.

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