PRJNA649447: Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model (bulk RNA-seq)
概要: 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.
项目整体设计: 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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Total RNA was extracted with RLT buffer |
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Bulk RNA libraries were prepared for sequencing using standard Illumina protocols. |
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rRNA- RNA |
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Illumina NovaSeq 6000 |
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unspecific |
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SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself.
Nature communications . 2021-03-30 [PMID:
33785765]
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.
eLife . 2021-06-21 [PMID:
34151773]
