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

Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation.
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DOI:
10.1016/j.cell.2016.07.026
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发表时间:
2016-09-08
期刊:
影响因子:
64.5
通讯作者:
Medzhitov R
Medzhitov R
中科院分区:
生物学1区
文献类型:
--
作者:
Wang A;Huen SC;Luan HH;Yu S;Zhang C;Gallezot JD;Booth CJ;Medzhitov R

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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, while 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.
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