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

Abstract

Ketogenic diet protects mice against influenza virus infection through γδ T cell expansion and metabolic adaptation. Putting mice on a keto diet Our immune responses to infections are influenced by several extrinsic factors, including weather, social interactions, and diet. Here, Goldberg et al. report that feeding mice a high-fat, low-carbohydrate ketogenic diet confers protection in the context of lethal influenza infection. By characterizing the immune response in the lungs, the authors identified that ketogenic diet promoted the expansion of γδ T cells in the lung. Using mice lacking γδ T cells, the authors have established the functional importance of these cells in conferring protection. Their findings suggest that γδ T cells improve barrier function in the lungs by modifying differentiation and function of the airway epithelial cells. 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.