Dataset Information

Mitochondrial damage drives T-cell immunometabolic paralysis after major surgery

ABSTRACT: Cytotoxic T cell (CTL) dysfunction is a key feature of immune paralysis following major surgery, significantly increasing the risk of severe nosocomial infections and contributing to elevated mortality in critically ill patients. The pathomechanisms of CTL dysfunction remain unclear. We report that reactive oxygen species (ROS) release by Myeloid-Derived Suppressor Cells, which transiently and unexpectedly emerge after major surgery, drives perioperative CTL immunoparalysis. This ROS release causes a critical accumulation of ROS within CTL, overwhelming their antioxidative defenses and severely compromising mitochondrial membrane potential. Consequently, oxidative phosphorylation is impaired, and CTL effector functions are inhibited. Additionally, stress-induced mitochondrial hyperfusion occurs, which disrupts fission-dependent mitochondrial translocation to the immunological synapse, exacerbating the bioenergetic failure. These processes result in substantial mitochondrial dysfunction, which could be partially reversed by treatment with the mitochondria-targeting antioxidant MitoTempo. Stabilizing mitochondrial function could serve as a promising clinical strategy for preventing and treating perioperative immune dysfunction.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Simone Kreth

PROVIDER: MSV000097035 | MassIVE | Tue Feb 04 05:52:00 GMT 2025

REPOSITORIES: MassIVE

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

Hirschberger Simon S Müller Martin B MB Mascolo Hannah H Seitz Melissa M Nibler Stefan S Effinger David D Lu Kun K Büch Joscha J Bender Martin M Kammerer Tobias T Peterß Sven S Kleigrewe Karin K Abele Miriam M Barth Teresa T Kushnir Olga O Imhof Axel A Dietzel Steffen S Wegener Bernd B Sowa Ralf R Vogel Frank F Lamm Peter P Tomasi Roland R Unger Kristian K Sperandio Markus M Kilger Erich E Kreth Simone S Hübner Max M

EMBO molecular medicine 20251103

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 ...[more]

PMID: 41184637

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