Format

Send to

Choose Destination
Cell. 2016 Sep 8;166(6):1512-1525.e12. doi: 10.1016/j.cell.2016.07.026.

Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation.

Author information

1
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT 06520, USA.
2
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Medicine (Nephrology), Yale University School of Medicine, New Haven, CT 06520, USA.
3
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
4
Yale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06520, USA.
5
Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
6
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: ruslan.medzhitov@yale.edu.

Abstract

Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so-called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here, we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore, glucose was necessary and sufficient for these effects. In contrast, nutritional supplementation protected against mortality from influenza infection and viral sepsis, whereas blocking glucose utilization was lethal. In both bacterial and viral models, these effects were largely independent of pathogen load and magnitude of inflammation. Instead, we identify opposing metabolic requirements tied to cellular stress adaptations critical for tolerance of differential inflammatory states. VIDEO ABSTRACT.

PMID:
27610573
PMCID:
PMC5555589
DOI:
10.1016/j.cell.2016.07.026
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center