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| Status |
Public on Jul 07, 2021 |
| Title |
Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model (bulk RNA-seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Impaired immunometabolic response in the elderly regulates inflammation-driven COVID-19 severity which confers the greatest risk of mortality. To investigate how aging compromises defense against COVID-19, we developed a model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain A59 (mCoV-A59) that recapitulated majority of hallmarks of COVID-19. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Ketogenic diet increases beta-hydroxybutyrate, expands tissue protective γδ T cells, deactivates the inflammasome and decreases pathogenic monocytes in lungs during aging. These data underscore the value of mCoV-A59 model to test mechanism and establishes harnessing of ketogenic immunometabolic checkpoint as potential treatment against COVID-19 in the elderly.
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| Overall design |
Aged mice (20-21 months old) were fed a KD or chow diet for 5 days and then intranasally infected with mCoV-A59. gdT cells were sorted from lungs.
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| Contributor(s) |
Ryu S, Shchukina I, Youm Y, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth C, Fernández-Hernando C, Suárez Y, Khanna KM, Horvath TL, Dietrich MO, Artyomov MN, Wang A, Deep Dixit V |
| Citation(s) |
34151773 |
| |
| Submission date |
Jul 29, 2020 |
| Last update date |
Jul 07, 2021 |
| Contact name |
Maxim Artyomov |
| E-mail(s) |
martyomov@email.wustl.edu
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| Organization name |
Washington University in St. Louis
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| Department |
Pathology and Immunology
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| Lab |
Artyomov Lab
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| Street address |
425 S Euclid Ave
|
| City |
St. Louis |
| State/province |
MO |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE155348 |
Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model |
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| Relations |
| BioProject |
PRJNA649447 |
| SRA |
SRP274103 |
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