Ribosome-Targeting Antibiotics Impair T Cell Effector Function & Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis, 2020, Sparwasser

Andy · Nov 26, 2020

Linezolid impairs T cell cytokine production by interfering with mitochondria

Mitochondrial translation is necessary for T cell function and pathology

Intracellular NAD+ and NADH levels are coupled to Th17 cytokine production

The cyclic peptide Argyrin C shows potential as an immunosuppressive drug

Summary
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 mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial 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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Open access, https://www.cell.com/immunity/fulltext/S1074-7613(20)30466-0

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Ribosome-Targeting Antibiotics Impair T Cell Effector Function & Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis, 2020, Sparwasser

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Ribosome-Targeting Antibiotics Impair T Cell Effector Function & Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis, 2020, Sparwasser

Andy Committee Member

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