Mitochondrial damage drives T-cell immunometabolic paralysis after major surgery.

ABSTRACT: Cytotoxic T cell (CTL) dysfunction is a hallmark of immune paralysis after major surgery, increasing susceptibility to severe nosocomial infections and contributing to mortality in critically ill patients. The mechanisms remain poorly understood. We demonstrate that reactive oxygen species (ROS) released by myeloid-derived suppressor cells (MDSC) transiently emerging after surgery, drive perioperative CTL immunoparalysis. These ROS damage CTL mitochondria, triggering secondary mitochondrial ROS amplification and overwhelming antioxidant defenses. The resulting oxidative cascade impairs oxidative phosphorylation and suppresses CTL effector function. Concurrently, stress-induced mitochondrial hyperfusion disrupts fission-dependent translocation to the immunological synapse, exacerbating bioe

SUBMITTER: Hirschberger S 

PROVIDER: S-EPMC12686421 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature