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Bacterial sepsis triggers an antiviral response that causes translation shutdown
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In: PMC (2019)
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Bacterial sepsis triggers an antiviral response that causes translation shutdown
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Abstract:
In response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses, as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. We determined that activation of the eukaryotic translation initiation factor 2-α kinase 2/eukaryotic translation initiation factor 2α (Eif2ak2/Eif2α) axis is the key mediator of translation initiation block in late-phase sepsis. Reversal of this axis mitigated kidney injury. Furthermore, temporal profiling of the kidney translatome revealed that multiple genes involved in formation of the initiation complex were translationally altered during bacterial sepsis. Collectively, our findings imply that translation shutdown is indifferent to the specific initiating pathogen and is an important determinant of tissue injury in sepsis.
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Keyword:
Research Article
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URL: http://www.ncbi.nlm.nih.gov/pubmed/30507610
https://doi.org/10.1172/JCI123284
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307966/
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