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Sci Immunol. 2019 Nov 15;4(41). pii: eaav2026. doi: 10.1126/sciimmunol.aav2026.

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

Author information

1
Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06519, USA.
2
Department of Immunobiology, Yale School of Medicine, New Haven, CT 06519, USA.
3
Novartis Institutes for BioMedical Research, 250 Massachusetts Ave, Cambridge, MA 02139, USA.
4
Department of Molecular Biophysics and Biochemistry, W.M. Keck Foundation Biotechnology Resource Laboratory, Yale University School of Medicine, New Haven, CT 06520, USA.
5
Department of Comparative Medicine, Yale School of Medicine, New Haven, CT 06519, USA. vishwa.dixit@yale.edu akiko.iwasaki@yale.edu.
6
Yale Center for Research on Aging, Yale School of Medicine, New Haven, CT 06519, USA.
7
Department of Immunobiology, Yale School of Medicine, New Haven, CT 06519, USA. vishwa.dixit@yale.edu akiko.iwasaki@yale.edu.
8
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
9
Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT, 06511, USA.

Abstract

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.

Comment in

PMID:
31732517
DOI:
10.1126/sciimmunol.aav2026

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