TY  - EJOU
AU  - Acierno, Carlo 
AU  - Carriero, Flavia 
AU  - Caturano, Alfredo 
AU  - Rubino, Valentina 
AU  - Sasso, Ferdinando Carlo 
AU  - D’Angelo, Salvatore 
AU  - Rinaldi, Luca 
AU  - Terrazzano, Giuseppe 

TI  - Hepatic Immunometabolic Reprogramming during Systemic Infections: Cellular Pathways Linking Innate Immunity and Metabolic Stress
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - Systemic infections expose the liver to convergent microbial, inflammatory, vascular, and metabolic stress signals. This narrative review synthesizes how hepatic immunometabolic reprogramming links innate immune sensing, bioenergetic stress, and sepsis-associated liver injury or dysfunction. It focuses on hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and hepatic stellate cells as a coordinated sinusoidal network rather than isolated cell compartments. Infection-derived pathogen-associated molecular patterns, host-derived damage-associated molecular patterns, cytokines, hypoxia, altered substrate flux, mitochondrial injury, endoplasmic reticulum stress, lipid remodeling, and redox imbalance are integrated into a temporal framework. Early responses may support host defense through acute-phase biosynthesis, microbial clearance, iron restriction, metabolic redistribution, and microvascular coordination. Persistent or spatially disorganized signaling may instead amplify nuclear factor kappa B and inflammasome activation, disrupt adenosine monophosphate-activated protein kinase-mechanistic target of rapamycin-hypoxia-inducible factor 1 alpha balance, impair sinusoidal perfusion, and promote cholestatic, hepatocellular, endothelial, and stromal maladaptation. Pre-existing metabolic dysfunction-associated steatotic liver disease, insulin resistance, aging, sex-related modifiers, and gut-liver axis disruption may lower the threshold for maladaptive trajectories. Evidence-graded biomarkers and clinical phenotypes are therefore framed as hypothesis-generating tools for trajectory-based translational studies.
KW  - Systemic infection; sepsis-associated liver dysfunction; sepsis-associated liver injury; hepatic immunometabolism; Kupffer cells; liver sinusoidal endothelial cells; hepatic stellate cells; mitochondrial dysfunction; inflammasome; adenosine monophosphate-activated protein kinase

DO  - 10.32604/biocell.2026.085405