tetano
Editor, Senior Moderator
Sci Immunol. 2019 Nov 15;4(41). pii: eaav2026. doi: 10.1126/sciimmunol.aav2026. [h=1]Ketogenic diet activates protective γδ T cell responses against influenza virus infection.[/h]
Goldberg EL[SUP]1,[/SUP][SUP]2[/SUP], Molony RD[SUP]2,[/SUP][SUP]3[/SUP], Kudo E[SUP]2[/SUP], Sidorov S[SUP]1[/SUP], Kong Y[SUP]4[/SUP], Dixit VD[SUP]5,[/SUP][SUP]2,[/SUP][SUP]6[/SUP], Iwasaki A[SUP]7,[/SUP][SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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.
Copyright ? 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PMID: 31732517 DOI: 10.1126/sciimmunol.aav2026
Goldberg EL[SUP]1,[/SUP][SUP]2[/SUP], Molony RD[SUP]2,[/SUP][SUP]3[/SUP], Kudo E[SUP]2[/SUP], Sidorov S[SUP]1[/SUP], Kong Y[SUP]4[/SUP], Dixit VD[SUP]5,[/SUP][SUP]2,[/SUP][SUP]6[/SUP], Iwasaki A[SUP]7,[/SUP][SUP]8,[/SUP][SUP]9[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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.
Copyright ? 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PMID: 31732517 DOI: 10.1126/sciimmunol.aav2026