Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation
Open accessAbstract
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.
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Restricting glucose utilization can be fatal in mice during viral infection, even though it is beneficial for fighting bacterial infections.
“Restricting glucose utilization can also be fatal in mice during viral infection, even though it proves beneficial for fighting bacterial infections195.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [195]
The mechanism underlying stress-induced worsening of end-organ function and death is likely a result of stress-induced IL6-dependent metabolic re-programming.
“The mechanism underlying this phenomenon is unclear, but likely is a result of stress-induced IL6-dependent metabolic re-programming similar to that which has been previously published by our group and others (Ganeshan et al., 2019; Luan et al., 2019; Wang et al., 2016; Wang A, 2019; Weis et al., 2017).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Wang et al., 2016
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- Authors
- Wang, A., Huen, S. C., Luan, H. H., Yu, S., Zhang, C., Gallezot, J.-D., Booth, C. J., & Medzhitov, R.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Medzhitov, Ruslan
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 166
- Issue
- 6
- Pages
- 1512-1525.e12
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5555589
- OpenAlex
- W2513994159
- Cited by
- 579
- References
- 7
- Citations by year
- 2026: 47 · 2025: 55 · 2024: 72 · 2023: 47 · 2022: 53 · 2021: 73 · 2020: 82 · 2019: 58 · 2018: 43 · 2017: 43 · 2016: 5 · 2014: 1
- FWCI
- 30.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA157461)
- National Institute of Allergy and Infectious Diseases (R01AI089771, R37AI046688, K08AI128745, T32AI007019, R01AI046688)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK079310, P30DK034989)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR007107)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- fasting metabolism, anorexia, sickness behavior, bacterial sepsis, viral sepsis, influenza, glucose utilization, dietary supplementation, tissue tolerance, inflammation, host defense, cellular stress adaptation
- MeSH terms
- Animals, Antimetabolites, Cells, Cultured, Deoxyglucose, Fasting, Glucose, Humans, Inflammation, Influenza, Human, Lipopolysaccharides, Listeriosis, Male, Mice, Inbred C57BL, Poly I-C, Nutritional Support, Sepsis, Disease Management, Mice, Transcription Factor CHOP, Illness Behavior
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