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

Andrew Wang, Sarah Huen, Harding H. Luan, Shuang Yu, Cuiling Zhang, Jean Dominique Gallezot, Carmen J. Booth, Ruslan Medzhitov

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)1512-1525.e12
JournalCell
Volume166
Issue number6
DOIs
StatePublished - Sep 8 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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