eLife | |
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice | |
Xinbo Zhang1  Carmen J Booth1  Yuki Yasumoto1  Seungjin Ryu2  Yun-Hee Youm2  Tamara Dlugos2  Vishwa Deep Dixit3  Carlos Fernández-Hernando4  Yajaira Suárez4  Marcelo O Dietrich4  Tamas L Horvath5  Andrew Wang6  Brandon Hilliard7  Hua Qing7  Kamal Khanna8  Maxim Artyomov9  Irina Shchukina9  | |
[1] Department of Comparative Medicine, Yale School of Medicine, New Haven, United States;Department of Comparative Medicine, Yale School of Medicine, New Haven, United States;Department of Immunobiology, Yale School of Medicine, New Haven, United States;Department of Comparative Medicine, Yale School of Medicine, New Haven, United States;Department of Immunobiology, Yale School of Medicine, New Haven, United States;Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, United States;Yale Center for Research on Aging, New Haven, United States;Department of Comparative Medicine, Yale School of Medicine, New Haven, United States;Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, United States;Department of Comparative Medicine, Yale School of Medicine, New Haven, United States;Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale School of Medicine, New Haven, United States;Yale Center for Research on Aging, New Haven, United States;Department of Immunobiology, Yale School of Medicine, New Haven, United States;Department of Internal Medicine, Yale School of Medicine, New Haven, United States;Department of Internal Medicine, Yale School of Medicine, New Haven, United States;Department of Microbiology, New York University Langone Health, New York, United States;Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States; | |
关键词: aging; MHV; coronavirus; inflammasome; gamma delta t cell; ketogenic diet; Mouse; | |
DOI : 10.7554/eLife.66522 | |
来源: eLife Sciences Publications, Ltd | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202107230634953ZK.pdf | 11233KB | download |