A1 Refereed original research article in a scientific journal
Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis
Authors: Almeida Luis, Dhillon-LaBrooy Ayesha, Castro Carla N, Adossa Nigatu, Carriche Guilhermina M, Guderian Melanie, Lippens Saskia, Dennerlein Sven, Hesse Christina, Lambrecht Bart N, Berod Luciana, Schauser Leif, Blazar Bruce R, Kalesse Markus, Muller Rolf, Moita Luis F, Sparwasser Tim
Publisher: CELL PRESS
Publication year: 2021
Journal: Immunity
Journal name in source: IMMUNITY
Journal acronym: IMMUNITY
Volume: 54
Issue: 1
First page : 68
Last page: 83
Number of pages: 22
ISSN: 1074-7613
eISSN: 1097-4180
DOI: https://doi.org/10.1016/j.immuni.2020.11.001
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/53076889
While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondria! translation in differentiating T cells, either with RAbos or through the inhibition of mitochondria! elongation factor G1 (mEF-G1) progressively compromised the integrity of the electron transport chain. Ultimately, this led to deficient oxidative phosphorylation, diminishing nicotinamide adenine dinucleotide concentrations and impairing cytokine production in differentiating T cells. In accordance, mice lacking mEF-G1 in T cells were protected from experimental autoimmune encephalomyelitis, demonstrating that this pathway is crucial in maintaining T cell function and pathogenicity.
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