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.
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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Growth Protocol: | - |
Treatment Protocol: | - |
Extract Protocol: | Total RNA was extracted with RLT buffer |
Library Construction Protocol: | Bulk RNA libraries were prepared for sequencing using standard Illumina protocols. |
Molecule Type: | rRNA- RNA |
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Library Layout: | PAIRED |
Library Strand: | - |
Platform: | ILLUMINA |
Instrument Model: | Illumina NovaSeq 6000 |
Strand-Specific: | unspecific |
Data Resource | GEN Sample ID | GEN Dataset ID | Project ID | BioProject ID | Sample ID | Sample Name | BioSample ID | Sample Accession | Experiment Accession | Release Date | Submission Date | Update Date | Species | Race | Ethnicity | Age | Age Unit | Gender | Source Name | Tissue | Cell Type | Cell Subtype | Cell Line | Disease | Disease State | Development Stage | Mutation | Phenotype | Case Detail | Control Detail | Growth Protocol | Treatment Protocol | Extract Protocol | Library Construction Protocol | Molecule Type | Library Layout | Strand-Specific | Library Strand | Spike-In | Strategy | Platform | Instrument Model | Cell Number | Reads Number | Gbases | AvgSpotLen1 | AvgSpotLen2 | Uniq Mapping Rate | Multiple Mapping Rate | Coverage Rate |
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