Ketogenic diet activates protective γδ T cell responses against influenza virus infection

EL Goldberg, RD Molony, E Kudo, S Sidorov… - Science …, 2019 - science.org
Science immunology, 2019science.org
Influenza A virus (IAV) infection–associated morbidity and mortality are a key global health
care concern, necessitating the identification of new therapies capable of reducing the
severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate,
high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding
resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby
enhancing antiviral resistance. Expansion of these protective γδ T cells required metabolic …
Influenza A virus (IAV) infection–associated morbidity and mortality are a key global health care concern, necessitating the identification of new therapies capable of reducing the severity of IAV infections. In this study, we show that the consumption of a low-carbohydrate, high-fat ketogenic diet (KD) protects mice from lethal IAV infection and disease. KD feeding resulted in an expansion of γδ T cells in the lung that improved barrier functions, thereby enhancing antiviral resistance. Expansion of these protective γδ T cells required metabolic adaptation to a ketogenic diet because neither feeding mice a high-fat, high-carbohydrate diet nor providing chemical ketone body substrate that bypasses hepatic ketogenesis protected against infection. Therefore, KD-mediated immune-metabolic integration represents a viable avenue toward preventing or alleviating influenza disease.
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