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Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis

(2021) IMMUNITY. 54(1). p.68-83
Author
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Abstract
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.
Keywords
TRANSCRIPTION FACTOR, DNA, RESPIRATION, ACTIVATION, INHIBITION, MEMBRANE, PATHWAYS, ARGYRIN, CHLORAMPHENICOL, OXAZOLIDINONE

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MLA
Almeida, Luis, et al. “Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis.” IMMUNITY, vol. 54, no. 1, 2021, pp. 68–83, doi:10.1016/j.immuni.2020.11.001.
APA
Almeida, L., Dhillon-LaBrooy, A., Castro, C. N., Adossa, N., Carriche, G. M., Guderian, M., … Sparwasser, T. (2021). Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis. IMMUNITY, 54(1), 68–83. https://doi.org/10.1016/j.immuni.2020.11.001
Chicago author-date
Almeida, Luis, Ayesha Dhillon-LaBrooy, Carla N. Castro, Nigatu Adossa, Guilhermina M. Carriche, Melanie Guderian, Saskia Lippens, et al. 2021. “Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis.” IMMUNITY 54 (1): 68–83. https://doi.org/10.1016/j.immuni.2020.11.001.
Chicago author-date (all authors)
Almeida, Luis, Ayesha Dhillon-LaBrooy, Carla N. Castro, Nigatu Adossa, Guilhermina M. Carriche, Melanie Guderian, Saskia Lippens, Sven Dennerlein, Christina Hesse, Bart Lambrecht, Luciana Berod, Leif Schauser, Bruce R. Blazar, Markus Kalesse, Rolf Mueller, Luis F. Moita, and Tim Sparwasser. 2021. “Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis.” IMMUNITY 54 (1): 68–83. doi:10.1016/j.immuni.2020.11.001.
Vancouver
1.
Almeida L, Dhillon-LaBrooy A, Castro CN, Adossa N, Carriche GM, Guderian M, et al. Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis. IMMUNITY. 2021;54(1):68–83.
IEEE
[1]
L. Almeida et al., “Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis,” IMMUNITY, vol. 54, no. 1, pp. 68–83, 2021.
@article{8697692,
  abstract     = {{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.}},
  author       = {{Almeida, Luis and Dhillon-LaBrooy, Ayesha and Castro, Carla N. and Adossa, Nigatu and Carriche, Guilhermina M. and Guderian, Melanie and Lippens, Saskia and Dennerlein, Sven and Hesse, Christina and Lambrecht, Bart and Berod, Luciana and Schauser, Leif and Blazar, Bruce R. and Kalesse, Markus and Mueller, Rolf and Moita, Luis F. and Sparwasser, Tim}},
  issn         = {{1074-7613}},
  journal      = {{IMMUNITY}},
  keywords     = {{TRANSCRIPTION FACTOR,DNA,RESPIRATION,ACTIVATION,INHIBITION,MEMBRANE,PATHWAYS,ARGYRIN,CHLORAMPHENICOL,OXAZOLIDINONE}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{68--83}},
  title        = {{Ribosome-targeting antibiotics impair T cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis}},
  url          = {{http://dx.doi.org/10.1016/j.immuni.2020.11.001}},
  volume       = {{54}},
  year         = {{2021}},
}

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