Tetracycline Antibiotics Induce Host-Dependent Disease Tolerance to Infection.
Immunity
; 54(1): 53-67.e7, 2021 01 12.
Article
em En
| MEDLINE
| ID: mdl-33058782
ABSTRACT
Several classes of antibiotics have long been known to have beneficial effects that cannot be explained strictly on the basis of their capacity to control the infectious agent. Here, we report that tetracycline antibiotics, which target the mitoribosome, protected against sepsis without affecting the pathogen load. Mechanistically, we found that mitochondrial inhibition of protein synthesis perturbed the electron transport chain (ETC) decreasing tissue damage in the lung and increasing fatty acid oxidation and glucocorticoid sensitivity in the liver. Using a liver-specific partial and acute deletion of Crif1, a critical mitoribosomal component for protein synthesis, we found that mice were protected against sepsis, an observation that was phenocopied by the transient inhibition of complex I of the ETC by phenformin. Together, we demonstrate that mitoribosome-targeting antibiotics are beneficial beyond their antibacterial activity and that mitochondrial protein synthesis inhibition leading to ETC perturbation is a mechanism for the induction of disease tolerance.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Tetraciclina
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Doxiciclina
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Sepse
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Fígado
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Pulmão
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Antibacterianos
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Mitocôndrias
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Immunity
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Portugal