Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. 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. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.
【저자키워드】 coronavirus, aging, Inflammasome, mouse, MHV, gamma delta T cell, Ketogenic diet, 【초록키워드】 Coronavirus infection, Mortality, T cells, severity, Infection, lung, immune, NLRP3 inflammasome, monocyte, Adults, T cell, Surveillance, COVID-19 infection, mice, Lungs, Impact, age, systemic inflammation, Protective, Glycolysis, Inflammatory, Potential treatment, mouse hepatitis virus, tissue, influenza infection, increased mortality, pathogenic, hallmark, Defense, adipose, beta coronavirus, MHV-A59, murine, risk of COVID-19, decrease, PROTECT, intranasally, inoculated, expand, Increasing, ketogenic, 【제목키워드】 Coronavirus infection, mice,